Последовательность BCMA- и GPRC5D-targeting Иммунотерапия в множестве миеломы: практическое руководство Европейской сети миеломы.

INTRODUCTION

Newly diagnosed multiple myeloma (MM) patients are increasingly treated with triplet and quadruplet regimens that incorporate CD38‐targeting antibodies, immunomodulatory drugs (IMiDs), and proteasome inhibitors (PIs). New agents with novel mechanisms of action are needed to treat patients who develop disease refractory to these agents at the time of first relapse or beyond. Various studies have demonstrated high activity of BCMA‐ and GPRC5D‐directed immunotherapies in these patients (Table 1 ). 4 , 13 , 15 , 16 There are currently two BCMA‐directed CAR T‐cell therapies approved for the treatment of patients with relapsed/refractory MM (cilta‐cel in patients with lenalidomide‐refractory MM after ≥1 prior treatment line, and ide‐cel for patients with triple‐class‐exposed MM after ≥2 prior treatments; Table 2 ). 1 , 4 , 6 , 16 Cilta‐cel binds simultaneously to two distinct BCMA epitopes, which confer high avidity binding, which may explain the higher activity of cilta‐cel compared to ide‐cel. 1 , 4 , 6 , 16 , 17 However, cilta‐cel therapy is also associated with a higher rate of severe CRS, severe ICANS, and delayed neurotoxicity, compared to ide‐cel. 2 , 4 , 5 , 6 , 7 , 16 , 17 , 18

In contrast to autologous CAR T‐cell products, T‐cell redirecting bispecific antibodies (BsAbs) and antibody‐drug conjugates are immediately available “off‐the‐shelf” drugs, allowing direct treatment in patients with aggressive relapse. The BCMA‐targeting BsAbs teclistamab, elranatamab, and linvoseltamab are approved for the treatment of triple‐class exposed MM, and talquetamab (same label) is currently the only approved GPRC5D‐targeting BsAb (Table 2 ). 11 , 12 , 19 , 20 The FcRH5‐targeting BsAb cevostamab is effective in heavily pretreated MM, but is currently not approved. 21 Efficacy of approved BCMA‐ and GPRC5D‐targeting BsAbs is comparable, and both are associated with similar risk of CRS and ICANS. However, infectious risk is higher with BCMA‐targeting BsAbs, 19 , 20 , 22 while talquetamab is associated with skin/nail disorders, oral adverse events such as dysgeusia, dysphagia, and dry mouth, as well as weight decrease, and less frequently, cerebellar toxicity. 12

The antibody‐drug conjugate belantamab mafodotin (belamaf) consists of an anti‐BCMA antibody covalently linked to the microtubule‐disrupting agent monomethyl auristatin F (MMAF). As a monotherapy, it has modest activity (overall response rate [ORR]: 32%) in patients with triple‐class refractory MM. 23 Corneal epithelial changes, resulting in blurred vision and dry eyes, are common with belamaf, but corneal toxicity can be effectively managed with extended dose intervals without impacting efficacy. 24 Patients receiving belamaf should undergo ophthalmic examinations before and during the first treatment cycles, and upon worsening of symptoms. 24 Belamaf received conditional approval by the FDA and EMA in 2020 but was withdrawn from the market in November 2022 by the FDA and February 2024 by EMA, following the results of the DREAMM‐3 trial showing similar PFS with belamaf versus pomalidomide‐dexamethasone. 23 , 25 However, more recently, results from two phase 3 trials showed superiority of belamaf‐bortezomib‐dexamethasone (BVd) and belamaf‐pomalidomide‐dexamethasone (BPd) over standard‐of‐care. 13 , 14 , 15 In July 2025, EMA approved both belamaf‐based combinations for the treatment of patients who received at least one prior therapy. The FDA approved BVd in October 2025 for patients who received at least 2 prior lines of therapy, including PI and IMiD.

TREATMENT SELECTION

Treatment choice for relapsed/refractory MM is increasingly complex because of the availability of multiple regimens and the absence of randomized studies that evaluate the best sequence of anti‐MM regimens. Clinical decision‐making regarding treatment choice and drug sequencing is guided by patient‐related factors, disease characteristics, patient preferences, prior therapy exposure and refractory status, availability of drugs, and impact of treatment regimens on subsequent therapies (Figure 1 ). The optimal sequencing of T‐cell redirecting BsAbs, CAR T‐cell therapies, antibody‐drug conjugates, and other therapies remains an area of active research, aiming at improving efficacy, minimizing toxicity, and enhancing cost‐effectiveness.

Here, the European Myeloma Network (EMN) provides a comprehensive overview of available evidence on sequential use of BCMA‐ and GPRC5D‐targeting immunotherapies, including the recently approved belamaf‐based regimens. 13 , 14 , 15 We also provide recommendations on how to best incorporate these novel therapies into the present treatment landscape, as well as guidance on the optimal sequence of these different immunotherapies to improve clinical outcomes of patients with MM.

RESISTANCE MECHANISMS IMPACTING SERIAL TREATMENT WITH BCMA‐ OR GPRC5D‐DIRECTED IMMUNOTHERAPIES

Because BCMA‐ and GPRC5D‐directed immunotherapies are now available in similar therapeutic settings, a key challenge is how to sequence these agents to optimize clinical outcomes. Understanding resistance mechanisms will be important to guide clinical practice (Figure 2 ). 26 Exposure to these novel immunotherapies may reduce target antigen expression or induce (functional) antigen loss, and thereby have a negative impact on the efficacy of subsequent therapies targeting the same tumor antigen. 27 In addition, there is increasing evidence that prior T‐cell immunotherapy has an impact on the efficacy of subsequent T‐cell immunotherapies through additional mechanisms, including selection of T‐cell‐resistant MM clones and impact on T‐cell quantity or quality. 28 , 29 In addition, if epitopes of two BsAbs/CARs targeting the same antigen are closely spaced, binding of one antibody/CAR may hinder the binding of another antibody/CAR to its respective target. Altogether, these effects may have implications for the proper use and efficacy of subsequent relapse regimens.

SEQUENCING BCMA‐ AND GPRC5D‐DIRECTED THERAPIES

In this section, we will discuss the available evidence that guides the sequencing of BCMA‐ and GPRC5D‐targeting modalities, which is currently based on nonrandomized prospective studies with limited numbers of patients and retrospective analyses. We focus on approved treatment options, but we will also briefly discuss sequencing of therapies in advanced stages of clinical development, including immunotherapies directed at other targets.

Sequencing BCMA‐directed therapies

The registrational studies of approved BCMA‐directed immunotherapies excluded patients who previously received BCMA‐directed therapy. 1 , 6 , 13 , 15 , 19 , 20 Although larger studies are needed, there is increasing evidence that patients who have been exposed to BCMA‐targeted therapy can still respond to subsequent therapy with a different anti‐BCMA modality. 30 , 31 However, the efficacy of a second BCMA‐directing modality is generally reduced by prior BCMA‐directed treatment, but this effect seems to be less pronounced when BCMA‐directed CAR T‐cell therapy is given first. 32

BCMA‐directed CAR T‐cell therapy in patients with prior noncellular BCMA‐directed therapy

Patients who previously received non‐cellular BCMA‐targeted therapy (ADC or BsAb) experienced substantially impaired duration of response and PFS following BCMA‐directed CAR T‐cell therapy, while response rates are only modestly reduced (Table 3 ). 33 , 34 , 35 , 37 , 38 , 39 , 40 , 41 This is clearly illustrated in cohort C of the CARTITUDE‐2 study which showed that clinical outcomes with cilta‐cel are inferior in patients previously exposed to non‐cellular BCMA‐targeting agents (ADC‐exposed group [ n = 13]: ORR 61.5%; median PFS 9.5 months; BsAb‐exposed group [ n = 7]: ORR 57.1%; median PFS 5.3 months), compared to results in BCMA‐naïve patients. 33 The safety profile of cilta‐cel in patients with prior BCMA exposure was consistent with that observed in BCMA‐naïve patients. 1 , 33

Similarly, in a real‐world study with 236 patients treated with cilta‐cel, prior BCMA‐directed therapy ( n = 33) was associated with an inferior response rate, compared to patients who were not previously BCMA exposed (ORR: 70% vs. 92%; ≥CR: 42% vs. 75%). 34 Median PFS was only 13.6 months for patients with prior BCMA‐directed therapy, while median PFS was not reached in all 236 patients (12‐month PFS: 68%). 34 Although patient numbers are limited, there was no difference in PFS across different types of prior BCMA‐targeted therapy (ADC versus BsAb versus CAR T‐cell therapy). 34

Furthermore, in a large cohort of 203 patients who received commercial ide‐cel, prior BCMA‐directed therapy ( n = 50; 25%) was an independent predictor for inferior outcomes (ORR: 74% vs. 88%; ≥CR: 29% vs. 48%; median PFS: 3.2 vs. 9.0 months for patients with prior BCMA‐directed therapy versus those without, respectively). 35 Although the number of patients was relatively small, the impact of prior BCMA‐targeting BsAbs ( n = 7) and ADCs ( n = 38) was more pronounced, compared to prior BCMA‐directed CAR T‐cell therapy ( n = 5; ORR with prior BsAb: 86%; prior ADC: 68%; prior CAR T‐cell therapy: 100%; and median PFS with prior BsAb: 2.8 months; prior ADC: 3.2 months; prior CAR T‐cell therapy: not reached). 35

A large retrospective CIBMTR analysis with 821 patients treated with standard‐of‐care ide‐cel also showed that prior non‐cellular BCMA‐directed therapy (14.1%; ADC [ n = 113] or BsAb [ n = 3]) was associated with inferior PFS and OS, compared to patients who did not receive prior BCMA‐directed therapy (median PFS: 5.3 months vs. 9.7 months; 1‐year OS: 52% vs. 70%). 36 Other real‐world studies also indicate that prior BCMA‐targeted therapies impair outcomes with BCMA‐directed CAR T‐cell therapy. 37 , 38 , 39 , 40 , 41 , 42 , 43

Inferior outcomes in patients with prior BCMA exposure may be related to the emergence of clones with reduced/absent BCMA expression or antigen shielding. 27 , 44 , 45 In addition, BCMA‐targeting BsAbs may impair T‐cell fitness, which has a negative impact on CAR T‐cell manufacturing (diminished expansion and reduced transduction efficiency) and the capacity of the derived CAR T‐cell products to kill MM cells. 29 , 46 Notably, in some BCMA retreatment studies, response to prior BCMA‐targeting BsAb was low (0%–29%), 33 , 35 which may reflect in part that these patients received treatment in phase 1 studies with potentially low doses of the BsAb, but may also indicate selection of a patient population with T‐cell‐resistant disease or with impaired T‐cell fitness. 33 To what extent response to prior BCMA‐targeted therapy affects response warrants further investigation. Finally, patients with prior BCMA‐targeted therapy typically received a greater number of prior therapies and were more likely to have penta‐drug‐refractory disease, compared to those without prior BCMA‐targeted therapy. 33 , 35 Such differences may also explain part of the worse efficacy outcomes in patients with prior BCMA‐targeted therapy.

Various studies demonstrate that responding patients had a longer time between the last BCMA‐targeted treatment and apheresis or CAR T‐cell infusion, compared to nonresponders. 33 , 34 , 35 , 36 For example, in a real‐world study, patients with last BCMA‐targeted therapy <6 months prior to cilta‐cel had lower response rates and PFS, compared to patients with last BCMA exposure ≥6 months (ORR: 54% vs. 94%; ≥CR: 31% vs. 56%; median PFS: 6.2 vs. 16.8 months). 34 Similarly, ide‐cel activity was worse in patients who had received prior noncellular BCMA‐directed therapy within 6 months of CAR T‐cell therapy. 36 This indicates that alternative therapies with different modes of action could be used to extend the duration of time between BCMA‐targeted therapies in order to improve the efficacy of CAR T‐cell therapy. 33 , 34 , 35 However, these results may be confounded by more indolent MM disease biology, allowing for more time between BCMA‐targeted therapies. 35 Further investigations are needed to define the optimal duration of BCMA‐free treatment interval to mitigate the negative impact of prior BCMA therapy. Another potential future strategy is to collect T‐cells earlier in disease course in patients who are expected to be eligible for CAR T‐cell therapy at a late stage, before sustained exposure to drugs with negative impact on T‐cell fitness (e.g., BsAbs). 47 However, additional studies are needed to evaluate the feasibility of preemptive T‐cell collection and its impact on the potency of the CAR T‐cell product.

BCMA‐targeting BsAbs in patients with prior BCMA‐directed therapy (CAR T‐cell therapy or ADC)

Although response rates are high, response duration and PFS are shorter in patients treated with BCMA‐targeting BsAbs after prior BCMA‐directed therapy than what has been observed in BCMA treatment‐naïve patients (Tables 4 and 5 ). 31 , 32 , 48 , 50 , 51 , 52 , 53 , 54 , 55 The safety profile of BsAbs in BCMA‐exposed patients is similar to that observed in BCMA treatment‐naïve patients. 32 , 48

In cohort C of the MajesTEC‐1 study, teclistamab was tested in 40 heavily pretreated patients, who were previously exposed to BCMA‐targeted therapy (ADC or CAR T‐cell therapy; 67.5% refractory to prior BCMA‐directed therapy). 48 The ORR with teclistamab was 55.2% (≥CR: 27.6) in patients with prior ADC and 53.3% (≥CR: 26.7%) with prior CAR T‐cell therapy. After a median follow‐up of 28.0 months, median PFS was 7.3 months in ADC‐exposed and 4.4 months in CAR T‐cell therapy‐exposed patients. 48 The efficacy of elranatamab was evaluated in 87 patients with prior exposure to BCMA‐targeted therapies in a pooled analysis of 4 MagnetisMM studies (59 patients with prior ADC; 36 patients with prior CAR T‐cell therapy; 8 patients with prior ADC and CAR T‐cell therapy). 32 The ORR was 42.4% (≥CR: 18.6%) in patients with prior ADC and 52.8% (≥CR: 19.4%) with prior CAR T‐cell therapy. Median PFS was longer in those with previous CAR T‐cell therapy versus prior ADC treatment (10.0 vs. 3.9 months). 32 In addition, a high response rate was reported with linvoseltamab in 10 patients with prior exposure to belamaf (≥PR: 70%), but no data on the durability of response were provided. 22 Similarly, several real‐world studies indicate that prior exposure to BCMA‐directed therapy impairs PFS with BCMA‐targeting BsAbs, compared to what was achieved in BCMA‐naïve patients. 31 , 50 , 51 , 52 , 53 , 55 , 56

Importantly, several studies suggest that a BCMA‐free interval may mitigate the negative effect of prior BCMA‐directed therapy on the efficacy of BCMA‐targeting BsAbs. 52 , 53 , 56 One study demonstrated that clinical outcomes with BsAbs were better in patients with disease relapse ≥1 year compared to early relapse (<1 year) post‐BCMA‐directed CAR T‐cell therapy (≥CR: 57.1% vs. 14.3%; median PFS: not reached vs. 3.1 months). 52 At the time of BsAb initiation, there were no differences in baseline characteristics associated with poor response between both patient groups (e.g., comparable absolute lymphocyte count, biomarkers for tumor burden, ferritin, and LDH). 52 Another study reported that patients with a BCMA‐free interval of >9 months had superior PFS with teclistamab, compared to patients with <9 months from last prior BCMA‐directed therapy exposure (median PFS: 8.1 vs. 2.5 months). 53 Similarly, in a large real‐world study with 509 patients, BCMA‐directed therapy in the previous 9 months was an independent predictor of poor response and shorter PFS to teclistamab (≥VGPR in patients >9 and ≤9 months since last BCMA‐directed therapy: 45% vs. 30%; median PFS: 6.6 vs. 1.8 months). 56 In this real‐world analysis, the impact of CAR T‐cell therapy within the prior 9 months on efficacy of teclistamab treatment was more pronounced than that of prior belamaf. 56 In contrast, in cohort C of the MajesTEC‐1 study response was comparable between patients who received prior BCMA‐directed therapy as last line of therapy versus those who did not (≥PR: 55.6% vs. 50.0%). 48 Additional studies are needed to better understand the impact of the timing of BsAb initiation in relation to the last exposure to a prior BCMA‐directed therapy.

Belamaf in patients with prior BCMA‐directed therapy (CAR T‐cell therapy or BsAb)

There are a few studies with limited numbers of patients that evaluated the efficacy of belamaf after prior BCMA‐directed therapy. In a real‐world observational study of belamaf in relapsed/refractory MM, 18 out of 94 patients had prior BCMA‐directed therapy (12 received CAR T‐cell therapy and 6 BsAb treatment). 57 Although these BCMA‐exposed patients were heavily pretreated with a median of 9 prior lines of therapy, belamaf yielded an ORR of 29% and there was no difference in PFS between patients who had been exposed to BCMA‐targeted drugs and those who were BCMA naïve. 57 Furthermore, the combination of belamaf and elotuzumab showed similar activity in patients with ( n = 4) or without ( n = 6) previous exposure to BCMA‐directed therapies. 58 In contrast, two retrospective studies with a limited number of patients showed that belamaf after BCMA‐targeting CAR T‐cell therapy had limited activity (≥PR: 0%–11% in 7–9 patients). 51 , 59 A limitation of these studies is that patients were heavily pretreated and mostly received single‐agent belamaf, 51 , 57 , 58 , 59 while belamaf is currently used in combination with bortezomib or pomalidomide in patients with early relapsed/refractory MM. 13 , 15 Because of the recent re‐approval of belamaf in patients who received at least one prior line of therapy (EMA) and the growing availability of T‐cell immunotherapies, further research is needed to guide the use of belamaf in patients with prior BCMA‐directed therapy.

Sequential use of different BCMA‐targeting BsAbs

A small retrospective study showed that teclistamab was not effective in eight patients previously exposed to another BCMA‐targeting BsAb (ORR: 12.5%; median PFS: 0.7 months). 53 Notably, a preclinical study showed that BCMA mutations do not result in universal resistance to BCMA‐targeting BsAbs, indicating that retreatment with an alternative BCMA‐targeting BsAb may be effective in a specific subset of patients. 27

Sequential cellular BCMA‐directed therapy: Same CAR T‐cell product

Retreatment with the same CAR T‐cell product is not effective, which is in part explained by the development of anti‐CAR antibodies. In the KarMMa study, 28 patients were retreated with ide‐cel at the time of progression. The ORR was only 21% (≥CR: 0%) with a median PFS of 1.0 months. 6 All 6 patients who achieved a response to retreatment were negative for anti‐drug antibodies, while none of the patients with anti‐drug antibodies responded. 6 Similarly, the development of anti‐cilta‐cel antibodies may explain why cilta‐cel retreatment was associated with limited anti‐MM efficacy and CAR T‐cell expansion. 60 Furthermore, retreatment at the time of progression was also largely ineffective with FCARH143, a fully human BCMA‐directed CAR T‐cell product. 44

Sequential cellular BCMA‐directed therapy: Different CAR T‐cell product

Several studies with limited patient numbers suggest that sequential BCMA‐directed CAR T‐cell therapy can be an efficacious treatment strategy if a different CAR T‐cell product is used. 51 , 61 , 62 , 63 For example, in a retrospective analysis of 68 patients with relapsed disease after BCMA‐directed CAR T‐cell therapy, promising activity was observed among those receiving another BCMA‐directed CAR T‐cell product ( n = 9; ≥PR: 89%; median PFS: 8.3 months). 51 In addition, administration of a fully human BCMA‐directed CAR T‐cell product (CT103A) was effective in all four patients, who developed progression after treatment with murine BCMA‐directed CAR T‐cells. 62 Notably, patients who were able to receive sequential BCMA‐directed CAR T‐cell therapy might have less aggressive disease, which may also affect treatment outcomes.

Allogeneic BCMA‐directed CAR T‐cells could be a future treatment option, especially in cases where T‐cell exhaustion is contributing to impaired activity of autologous CAR T‐cells. However, extensive genetic engineering and the still remaining risk of allo‐rejection, and thus the limited persistence of allogeneic CAR T‐cells, may negatively affect the duration of response. Interestingly, P‐BCMA‐ALLO1 induced high response rates in both BCMA‐naïve ( n = 9; ORR: 100%) and BCMA‐exposed patients ( n = 14; either prior CAR T‐cell therapy, BsAb, and/or ADC; ORR: 86%). 64 However, response duration was not reported because of the short follow‐up. 64

Target switch

Because of the increasing use of BCMA‐directed therapies, which can lead to reduced or complete loss of BCMA expression, 6 , 16 , 27 , 44 , 45 , 65 , 66 T‐cell immunotherapies targeting alternative antigens were developed. The efficacy of sequential immunotherapy may be improved by target switch.

Non‐BCMA‐targeting BsAb in patients with prior BCMA CAR T‐cell therapy

Several studies suggest that non‐BCMA‐targeting BsAbs may be more effective to manage relapse post‐BCMA‐directed CAR T‐cell therapy, compared to sequencing two different BCMA‐directed modalities (Table 4 ). 67 , 68 , 69 First, GPRC5D‐targeting BsAbs provide substantial clinical benefit in patients who relapse after BCMA‐directed CAR T‐cell therapy. 12 , 67 , 68 , 70 , 71 In MonumenTAL‐1, 78 patients had received previous T‐cell redirecting therapy (CAR T‐cell therapy [ n = 57] and/or BsAb [ n = 26]; most were BCMA‐directed [96%]). 12 , 67 , 68 The efficacy of talquetamab was not impaired by prior BCMA‐directed CAR T‐cell therapy (ORR: 72%; median PFS: 13.0 months). 12 , 68 In the prior CAR T‐cell therapy group, ORR was comparable in those who received BCMA‐directed CAR T‐cell therapy as the immediate prior line (74%), compared to patients who had received BCMA‐directed CAR T‐cells before the last line of therapy (68%). 12 , 68 Patients with prior CAR T‐cell therapy had a higher overall infection rate and slightly higher frequency of severe infections, compared to T‐cell‐redirecting therapy‐naïve patients. 68 Similarly, in a German real‐world analysis, prior BCMA‐directed CAR T‐cell therapy did not negatively affect response and PFS with talquetamab. 71

The FcRH5‐targeting BsAb cevostamab is also effective after BCMA‐directed CAR T‐cell therapy. 72 In cohort A1 of the phase 1/2 CAMMA2 study, cevostamab was evaluated in patients who were triple‐class refractory and had received a prior BCMA‐directed ADC or CAR T‐cell therapy (prior BCMA‐targeting BsAbs were not permitted). 72 Preliminary results demonstrate a 73% ORR with ≥CR in 27% of 11 heavily pretreated patients with prior BCMA‐directed CAR T‐cell therapy. 72 , 73 With a median follow‐up of 11 months, 5 of 8 responders were still in response. Adverse events were consistent with the known safety profile of cevostamab. 72

BsAbs may also have an important role as a consolidation/maintenance strategy to enhance the cytotoxic activity of BCMA‐directed CAR T‐cells. Preclinical studies observed enhanced anti‐MM activity with increased levels of activation and proliferation of CAR‐negative T‐cells when BsAbs were combined with cilta‐cel. 46 The synergy between BsAbs and cilta‐cel was most pronounced at suboptimal CAR T‐cell:tumor cell ratios, representative of high tumor burden. 46 Based on these findings, several clinical studies are currently evaluating the efficacy of BsAbs targeting a different antigen (e.g., talquetamab or cevostamab) as consolidation after BCMA‐directed CAR T‐cell therapy, with the goal of sequential T‐cell engagement against 2 different antigens to eliminate residual disease. 74 In addition, the phase 2 aMMbition trial evaluates consolidation with alternating cycles of teclistamab‐daratumumab and talquetamab‐daratumumab after cilta‐cel infusion in patients with standard‐risk newly diagnosed disease.

BCMA‐directed CAR T‐cell therapy in patients with previous exposure to non‐BCMA‐targeting BsAbs

Irrespective of their target, BsAbs should be avoided prior to T‐cell apheresis for CAR T‐cell production, because of increased risk of manufacturing failure and out‐of‐specification (OOS; not meeting predefined acceptance criteria) products, even with a limited number of BsAb administrations prior to apheresis. 34 , 75 , 76 , 77 This may be explained by the negative effect of BsAbs on T‐cell fitness and skewing of T‐cells toward terminal effector differentiation, resulting in diminished expansion and reduced transduction efficiency during CAR T‐cell generation. 29 , 46 , 76 , 78 , 79 In addition, similar to BCMA‐targeting BsAbs, administration of non‐BCMA‐targeting BsAbs before apheresis impairs the efficacy of BCMA‐directed CAR T‐cell therapies. 38 , 80 First, the use of talquetamab prior to T‐cell apheresis reduced PFS with ide‐cel in a French real‐world study. 38 Also in a German retrospective multicenter study, talquetamab before apheresis impaired response to CAR T‐cell therapy (ide‐cel and cilta‐cel), but this effect was less pronounced than what was observed when BCMA‐targeting BsAbs were administered prior to apheresis. 80 The shortest PFS after BCMA‐directed CAR T‐cell therapy was observed in patients who had received both BCMA‐ and GPRC5D‐targeting BsAbs before apheresis. 80 However, several studies have shown that talquetamab can be effectively and safely used as bridging therapy after T‐cell apheresis in patients scheduled for BCMA‐directed CAR T‐cell therapy. 75 , 77 , 80 , 81 , 82 Talquetamab induced a higher response rate in heavily pretreated MM patients, compared to chemotherapy or antibody‐based regimens. 75 This is clinically relevant because there is increasing evidence that reducing tumor load with bridging therapy improves both safety profile and efficacy after CAR T‐cell infusion. 83 , 84 , 85 , 86 However, it is currently unknown whether a short course of talquetamab bridging could select for GPRC5D‐negative clones and thereby influence the efficacy of subsequent treatment with a similar or different GPRC5D‐directed modality. Therefore, talquetamab bridging should be reserved for patients with no other bridging options.

Sequential use of BsAbs targeting different tumor antigens

Sequential use of BsAbs with different target antigens is feasible, but the efficacy of the second BsAb is typically reduced, compared to the activity of the first BsAb, 30 , 68 , 87 , 88 , 89 which may be related to reduced T‐cell fitness due to long‐term T‐cell activation. 29 , 78 , 90

BCMA ‐‐>GPRC5D

Efficacy of talquetamab in the MonumenTAL‐1 study was substantially lower in patients with prior BCMA‐targeting BsAb therapy (ORR: 58%; median PFS: 3.9 months), compared to what was observed in patients who were not previously exposed to BsAbs (ORR: 69%–74%; median PFS: 7.5–11.2 months). 12 , 67 , 68 Notably, the ORR was inferior in patients who received a BCMA‐targeting BsAb as immediate prior line (29%) compared to those who received BCMA‐targeting BsAbs before the last line of therapy (68%), 12 , 68 which may be explained by recovery of T‐cell fitness during treatment without a BsAb. Interestingly, talquetamab‐induced T‐cell activation was less pronounced in patients with prior BsAb versus those with prior CAR T‐cell therapy, suggesting more T‐cell exhaustion in patients who were already treated with a BsAb. 12 , 68 Patients with prior BsAb had similar rates of infections, cytopenias, CRS, and on target/off tumor‐related AEs (e.g., dysgeusia) as patients with prior CAR T‐cell therapy. 12 , 68 Similarly, a real‐world analysis of talquetamab in 138 relapsed/refractory MM patients showed that prior BCMA‐targeting BsAb treatment was an independent predictor of impaired response and PFS (≥PR: 33.3% vs. 74.0%; median PFS: 2.8 vs. 7.9 months in patients with or without prior BCMA‐targeting BsAb, respectively). 71 Another retrospective single‐center study also showed that receiving a BCMA‐targeting BsAb prior to talquetamab results in inferior efficacy, compared to prior CAR T‐cell therapy or no prior BCMA‐directed therapy. 91

GPRC5D ‐‐>BCMA

Patients who develop disease progression following talquetamab treatment can be effectively treated with a second BsAb. 87 In the MonumenTAL‐1 study, 162 of the 297 patients treated with talquetamab received at least one subsequent therapy. 87 The ORR with non‐GPRC5D‐targeting BsAbs ( n = 23, 83% BCMA‐targeting BsAbs) was 60.9% as first line of therapy post‐talquetamab, which was superior compared to conventional therapies (chemotherapy‐based regimens: n = 48, ORR: 18.8%; PI‐ or IMiD‐based regimens: n = 43, ORR: 20.9%; CD38‐antibody‐containing regimens: n = 27, ORR: 33.3%). 87 Importantly, response to prior talquetamab was similar among both responders and nonresponders to non‐GPRC5D BsAbs as subsequent therapies. 87 Response duration was not reported. 87

BCMA or GPRC5D‐‐> FcRH5

Prior exposure to BCMA‐targeting BsAbs led to a lower response rate with cevostamab. 73 , 89 In cohort A2 of the CAMMA 2 study, cevostamab was evaluated in patients with previous exposure to BCMA‐targeting BsAbs. Twenty‐one triple‐class refractory patients with a median of 8 prior lines of therapy were enrolled. 73 The ORR was only 10% (CR: 5%). 73 Lower cytokine release was observed in patients with prior BCMA‐targeting BsAb exposure, compared to those exposed to other BCMA‐targeted therapies (CAR T‐cells or ADC). 73 The frequency of PD‐1 + and TIGIT + T‐cells was higher in peripheral blood at baseline in patients with prior BCMA‐targeting BsAb exposure, compared to patients previously exposed to CAR T‐cell therapy or ADCs, 73 suggesting that T‐cell exhaustion contributes to the poor response rate and decreased cytokine release. 73 A washout period of 4 months was required between discontinuation of prior BsAb and first cevostamab dose, but the exact interval between both BsAbs was not reported. 73 Prior exposure to talquetamab did not negatively affect response to cevostamab. 87 However, patient numbers were small ( n = 5), and the durability of response was not reported. 87

Sequential use of BsAbs targeting different tumor antigens: Mitigation strategies

There is preliminary evidence that alternative therapies to increase the interval between distinct BsAbs may improve the efficacy of the second BsAb, potentially by allowing T‐cells to recover from previous BsAb exposure. 12 , 68 , 71 Additional studies are needed to explore the optimal timing between different BsAbs and to investigate whether bridging therapy that incorporates drugs with a positive impact on T‐cell fitness (e.g., pomalidomide) can enhance the efficacy of sequential BsAb therapy. CELMoDs (iberdomide and mezigdomide), which have more potent immunostimulatory effects compared to IMiDs, also hold promise, as they can mitigate T‐cell exhaustion. 92

Combination strategies may also improve efficacy in patients with prior BsAb exposure. Notably, in the TRIMM‐2 study, adding daratumumab, or daratumumab plus pomalidomide, increased both response rate and PFS, particularly in patients with previous exposure to BCMA‐targeting BsAbs or BCMA‐directed CAR T‐cell therapy, 93 , 94 compared to what was observed with talquetamab monotherapy in these subgroups. 12 Similarly, talquetamab combined with PD‐1 inhibitor cetrelimab elicited deep and durable responses in 19 patients with prior BsAb therapy (95% received a BCMA‐targeting BsAb; 95% as immediate prior line of therapy) in the TRIMM‐3 study with an ORR of 68.4% (≥CR: 31.6%) and 6‐month PFS of 61.5%. 95 Combination therapy with CELMoDs or costimulatory BsAbs may also mitigate T‐cell exhaustion and improve efficacy of T‐cell therapies. 96 , 97

Non‐BCMA‐targeting BsAb in patients who previously received belamaf

Several studies indicate that belamaf has no negative impact on subsequent treatment with GPRC5D‐targeting BsAbs (Table 5 ). 49 , 88 For example, in the MonumenTAL‐1 study, talquetamab induced a 68.2% ORR in 44 heavily pretreated patients who were also exposed to a BCMA‐targeting ADC. 49 After a median follow‐up of 16.3 months, median PFS was not yet reached. 49

Cevostamab was effective in 10 patients with triple‐class refractory disease and prior BCMA‐directed ADC exposure in the CAMMA 2 study (ORR was 60% [CR: 10%]). 73 Moreover, a recent update from the DREAMM‐7 study showed that BsAb treatment as any subsequent line of therapy ( n = 10; cevostamab, talquetamab, or teclistamab) was feasible following BVd treatment with a promising response duration of 11.7 months. 98

Belamaf in patients with previous exposure to non‐BCMA‐targeting BsAbs

Prior talquetamab appears to have no negative impact on response to belamaf monotherapy (≥PR: 33% in nine patients). 87 However, studies with larger numbers of patients are needed to draw reliable conclusions.

Sequential CAR T‐cell therapy with target switch

Several GPRC5D‐directed CAR T cell therapies are in clinical development with promising efficacy in patients with advanced MM, including those with previous BCMA‐directed CAR T‐cell treatment. 99 , 100 , 101 , 102 , 103 , 104 Adverse events associated with GPRC5D‐targeting CAR T‐cell therapy include skin‐ and nail‐disorders, and taste changes, as well as infrequently, cerebellar toxicity. 99 , 100 , 104

In a phase 1 dose‐escalation study, MCARH109 showed promising efficacy in 17 heavily pretreated patients (median of 6 prior lines of therapy, 47% BCMA‐directed CAR T‐cell therapy exposed). 99 , 104 The ORR across all 4 dose levels was 71% (41% ≥CR) with a median response duration of 8.6 months 99 , 104 with similar ORR in patients with prior BCMA‐directed CAR T cell therapy (75%). 99 , 104 Comparable results were observed with arlo‐cel treatment (this product uses the same CAR construct as used in MCARH109). 100 Both ORR and PFS following arlo‐cel infusion (25–450 × 10 6 CAR T cells) were not notably impacted by previous exposure to BCMA‐directed modalities, including BCMA‐directed CAR T‐cell therapy (ORR: 79% vs. 95%; median PFS: 19.0 vs. 18.3 months in patients with [ n = 38] or without prior BCMA‐directed therapy [ n = 41], respectively). 100 , 105 The ongoing phase 2 QUINTESSENTIAL trial evaluates arlo‐cel in patients with previous exposure to BCMA‐directed therapies.

A Chinese phase 2 study showed that GPRC5D‐directed CAR T‐cell therapy induced a high response rate (ORR: 84%; ≥CR: 35%) in 37 patients who were previously treated with BCMA‐directed CAR T‐cell therapy. 106 However, median PFS was only 4.5 months, which may be related to a high proportion of patients with a high‐risk profile (extramedullary disease: 57%; high tumor burden: 41%). 106 Notably, median PFS was not yet reached for the subset of patients who achieved a CR ( n = 13). 106 Furthermore, two other Chinese studies also showed that GPRC5D‐directed CAR T‐cells can be effective in patients who were previously treated with BCMA‐directed CAR T‐cell therapy. 101 , 102

Non‐BCMA‐directed CAR T‐cell therapy in patients who previously received belamaf

Although only evaluated in a small number of patients, GPRC5D‐directed CAR T‐cell products have high activity in patients who received prior belamaf treatment. 100

RECOMMENDATIONS

Because BCMA‐ and GPRC5D‐directed immunotherapies are moving to earlier lines of treatment and because patients are increasingly likely to receive more than one of these novel therapies during their disease course, optimizing treatment sequencing becomes essential to enhance overall outcomes for patients with MM. Key recommendations are shown in Table 6 .

Practical considerations when selecting the first BCMA‐ or GPRC5D‐directed immunotherapy

An increasing number of patients will have disease exposed or refractory to PIs, lenalidomide, and CD38‐targeting antibodies at first relapse. BCMA‐directed therapy is currently the preferred option to treat patients who develop disease refractory to these agents in the early relapse setting. 107 At this moment, cilta‐cel and belamaf‐based regimens (FDA approved only BVd for patients who received at least 2 prior therapies) are approved for use in first relapse and beyond, while ide‐cel is licensed for use in triple‐class exposed patients with at least 2 prior therapies and BsAbs in triple‐class exposed patients who received at least 3 (EMA) or 4 (FDA) prior lines of therapy (Table 2 ). Lack of head‐to‐head comparisons between the different BCMA‐targeting modalities makes selection challenging. Based on available evidence, we recommend to use CAR T‐cell therapy first in patients who can receive this treatment (determined by eligibility criteria [focus on organ function and performance status, rather than strict age limits] as well as availability/reimbursement issues), based on the high response rates and durable remissions with improvements in quality of life after the single CAR T‐cell infusion, especially in patients with high‐risk disease including those with extramedullary involvement. 1 , 2 , 3 , 4 , 5 , 6 , 16 , 108 In addition, relapse after CAR T‐cell therapy can be effectively treated with BsAbs (especially with target switch). 12 , 67 , 68 , 70 , 71 Belamaf‐based regimens could also be considered in patients who develop disease progression following CAR T‐cell infusion, as some studies with limited sample size demonstrated that response to belamaf monotherapy was not affected by prior BCMA‐directed therapy. 57 , 58 In contrast, previous therapy with BCMA‐targeting BsAbs or belamaf may negatively affect the efficacy of BCMA‐directed CAR T‐cell therapy, particularly in the absence of a BCMA‐free interval. 33 , 34 , 35 , 37 , 38 , 39 , 40 , 41 , 80 However, bridging therapy with GPRC5D‐directed BsAbs (initiation after apheresis) can be considered because this allows for rapid disease control and may thereby improve the efficacy of consecutive BCMA‐directed CAR T‐cell therapy. 77 , 80 , 81 , 82 We discourage the use of BCMA‐targeting BsAbs as bridging therapy to prevent reduced or loss of BCMA antigen expression or masking of BCMA expression, and ensure optimal CAR T‐cell efficacy. 27 , 75 Although there are no direct head‐to‐head comparisons between cilta‐cel and ide‐cel, we currently favor the use of cilta‐cel because of the markedly superior response and PFS with this CAR T‐cell product versus ide‐cel, apart from patients with a history of neurological disorders or pre‐existing cytopenias. 1 , 4 , 7 , 16 , 17

Not all patients are suitable candidates for CAR T‐cell therapy because of frailty or the presence of co‐morbidities such as cardiac, neurological, and pulmonary disorders. Moreover, access to CAR T‐cell therapy remains limited because of costs, complex logistics, and manufacturing limitations. Based on efficacy and manageable toxicity profile, belamaf‐based combination regimens should be considered at the time of first relapse in patients who are not eligible for CAR T‐cell therapy, or in case CAR T‐cell therapy is not available within a short time frame. 13 , 15 Triple‐class exposed MM patients who are unable to timely receive CAR T‐cell therapy may also benefit from BsAb treatment, which is associated with less severe CRS, neurotoxicity, and cytopenias, compared to CAR T‐cell therapy. 8 , 10 , 11 , 12 , 19 In addition, patients with aggressive relapse or rapid increase in tumor burden may benefit from off‐the‐shelf, readily available treatment options like BsAbs or belamaf‐based regimens, because CAR T‐cell therapy requires a more complex manufacturing process.

Besides approval status and reimbursement policies, the choice between belamaf and BsAbs is influenced by differences in safety profile (ocular toxicity with belamaf, infections with BCMA‐targeting BsAbs, and oral toxicity with GPRC5D‐targeting BsAbs). 12 , 13 , 15 , 19 , 20 , 22 , 24 GPRC5D‐targeting treatment is a preferred first option for patients who are expected to be eligible for BCMA‐directed CAR T‐cell therapy at a later stage or who have an increased risk of infectious complications (e.g., patients with pulmonary/cardiac comorbidities). Choice of partner drug for belamaf depends in part on exposure to other anti‐MM agents and refractory status. Patients who develop disease progression while receiving lenalidomide may benefit most from BVd, with a switch from an IMiD to a PI (so‐called class switch). 109 On the other hand, BPd is probably the best option for patients with recent exposure to a PI. Treatment selection is also influenced by patient characteristics, with BPd being preferred in patients with neuropathy or those with limited mobility (pomalidomide is an oral drug). Bortezomib may be preferred in patients with a history of frequent infections, because infections were less frequent with BVd compared to BPd (grade ≥3: 31% versus 49%), possibly because of a lower neutropenia rate when bortezomib was used as a combination partner. 13 , 15

Practical considerations when using a second BCMA‐ or GPRC5D‐directed immunotherapy

Several studies have shown that sequential immunotherapy is feasible and often more effective than other types of anti‐MM therapy, 12 , 30 , 69 , 87 , 110 , 111 but the sequence of agents is essential to maximize the efficacy of sequential BCMA‐ and GPRC5D‐directed therapy. 30 , 69 , 111 Currently available data suggest that a switch from a BCMA‐ to GPRC5D‐targeted immunotherapy is more effective than sequential use of different BCMA‐directed modalities. 12 , 99 , 104 Similarly, a switch from GPRC5D‐targeted therapy to BCMA‐directed treatment can be an effective option for the treatment of relapsed/refractory MM. 87

If target switch is not possible after previous BCMA‐exposure, then a second BCMA‐directed therapy can be considered, but we recommend performing diagnostic tests to exclude BCMA antigen loss by using flow cytometry or immunohistochemistry, as well as cytogenetic analysis to exclude biallelic BCMA deletion to avoid futile and costly BCMA‐directed therapy. 45 In the near future, molecular tests to detect BCMA mutations and evaluation of T‐cell fitness could further aid in providing guidance on the type of second T‐cell immunotherapy (modality and target). 27 , 29 , 45 , 112 In addition, the available evidence suggests that a BCMA‐free interval of approximately 6–9 months results in improved clinical outcomes when sequencing two BCMA‐directed therapies. 33 , 34 , 35 , 36 , 52 , 53 , 56 Such spacing between BCMA‐directed therapies may facilitate recovery of T‐cell fitness or re‐emergence of BCMA‐expressing subclones. However, a longer interval between therapies may also be a surrogate marker for less aggressive disease biology. 56 A better understanding of the impact of duration and timing of prior BCMA‐targeted therapy is urgently needed.

When considering sequential use of BsAbs with different targets, there is increasing evidence that a BsAb‐free interval may improve efficacy of the second BsAb, and therefore, an alternative treatment could be considered prior to the second BsAb. 12 , 68 Although more information and broadly available biomarkers are needed to define an optimal washout period that allows for T‐cell recovery and improvement of T‐cell fitness, available evidence suggests that a window of at least 6 months is associated with superior outcomes with the second BsAb treatment. However, in extensively treated MM patients, selecting an alternative treatment option can be challenging.

CONCLUSIONS AND FUTURE PROSPECTS

In this guideline, we provide recommendations to optimize the efficacy of BCMA‐ and GPRC5D‐directed therapies in MM (Table 6 ). Notably, these recommendations are currently based on prospective studies with a limited number of patients or retrospective studies without direct comparisons between specific treatment sequences. Although clinical trials and real‐world studies provide generally consistent results, further investigations are needed to define the optimal window between targeted immunotherapies. Considering the recent re‐approval of belamaf and the growing availability of T‐cell immunotherapies, additional research is particularly needed on how to sequence BCMA‐ and GPRC5D‐directed immunotherapies when used in earlier lines of therapy, as current recommendations are mainly based on studies in advanced MM. Next to real‐world studies, prospective studies are being initiated to evaluate the efficacy of a specific treatment sequence in early relapsed/refractory MM. For example, the prospective BelaMi trial will investigate the sequence of belamaf combined with mezigdomide and dexamethasone after prior CAR T‐cell therapy). Next to genomic analyses, such studies should also evaluate whether a certain immune signature can be used to guide future clinical decision‐making (e.g., to select patients who may benefit from a second T‐cell‐based immunotherapy).

Importantly, recommendations may evolve when ongoing studies in earlier stages of disease provide new insights or upon the approval of new immunotherapies, including those targeting novel tumor‐associated antigens. 21 , 100 , 113 , 114 , 115 Ongoing studies are also exploring whether antigen escape or T‐cell exhaustion may be mitigated by limiting the duration of BsAb treatment and to what extent fixed‐duration BsAb treatment affects efficacy of serial treatment with different BCMA‐ or GPRC5D‐targeting modalities. 115 , 116 , 117 In addition, there is increasing preclinical and clinical evidence that simultaneously targeting multiple tumor‐associated antigens may improve response duration by maximizing tumor eradication in the presence of tumor heterogeneity and by preventing disease progression due to loss of a single antigen. 113 , 118 , 119 , 120 , 121 First, dual targeting CAR T‐cell strategies (e.g., BCMA/GPRC5D dual‐targeting CAR T‐cells) are currently evaluated in clinical trials, based on promising results from preclinical studies. 113 , 120 In addition, dual antigen targeting with the combination of teclistamab and talquetamab was evaluated in the RedirecTT‐1 study with a high ORR of 80% (≥CR: 52%) in 40 patients treated with the recommended phase 2 regimen. 119 High efficacy with this combination regimen was also observed in patients with extramedullary disease (ORR: 61%). 119 Furthermore, several clinical studies evaluating trispecific antibodies have shown promising antitumor activity. 118 , 121 JNJ‐5322 (ramantamig), a trispecific antibody targeting CD3, BCMA and GPRC5D, demonstrated a manageable safety including a low grade CRS profile with only one step‐up dose. 118 JNJ‐5322 showed high efficacy in heavily pretreated MM, as evidenced by an ORR of 100% (≥CR: 70%) in patients naïve to BCMA/GPRC5D‐directed therapies treated at the recommended phase 2 dose (100 mg Q4W), which translated into a 12‐month PFS of 95%. 118 Similarly, ISB 2001, a BCMAxCD38xCD3 trispecific antibody, induced deep and durable responses at active doses (≥50 µg/kg) in a phase 1 study with 35 heavily pretreated MM patients (ORR: 79%; ≥CR: 30%). 121 A high response rate with ISB 2001 was also observed in the subset of patients ( n = 15) who had received prior BCMA‐directed therapies (ORR: 73%; ≥CR: 27%). 121 Although targeting multiple antigens simultaneously appears to increase efficacy, it will be important to demonstrate in clinical trials that this strategy is superior compared to the classical approach of serial treatment with mono‐targeting agents with target switch.

There are currently no studies available that provide information on the feasibility of sequential treatment with two different GPRC5D‐targeting modalities, but this information will be increasingly relevant because of multiple GPRC5D‐targeting CAR T‐cell therapies (e.g., arlo‐cel) in advanced stages of clinical development. 99 , 101 , 102 , 103 , 104 , 105 Also, GPRC5D‐targeting ADCs, which do not rely on immune fitness, are evaluated in clinical trials. 122 Because GPRC5D antigen escape is commonly observed, 27 , 99 , 104 these studies should monitor GPRC5D expression in patients who previously received a GPRC5D‐directed modality.

Altogether, we expect that the increasing availability of highly effective immunotherapies in both early and late stages of the disease, combined with a better understanding of synergistic sequencing pathways, will further improve the survival of MM patients.

AUTHOR CONTRIBUTIONS

Niels W. C. J. Donk : Conceptualization; methodology; writing—original draft; writing—review and editing. Philippe Moreau : Conceptualization; writing—original draft; writing—review and editing; methodology. Jesus F. San‐Miguel: Conceptualization; writing—original draft; writing—review and editing; methodology. Maria‐Victoria Mateos : Conceptualization; writing—original draft; writing—review and editing; methodology. Meletios A. Dimopoulos : Methodology; writing—review and editing; writing—original draft; conceptualization. Sonja Zweegman : Conceptualization; writing—original draft; writing—review and editing; methodology. Francesca Gay : Methodology; writing—review and editing; writing—original draft; conceptualization. Monika Engelhardt : Conceptualization; writing—original draft; writing—review and editing; methodology. Roberto Mina : Methodology; writing—review and editing; writing—original draft; conceptualization. Elena Zamagni : Conceptualization; writing—original draft; writing—review and editing; methodology. Michel Delforge : Methodology; writing—review and editing; writing—original draft; conceptualization. Meral Beksac : Conceptualization; writing—original draft; writing—review and editing; methodology. Andrew Spencer : Methodology; writing—review and editing; writing—original draft; conceptualization. Fredrik Schjesvold : Conceptualization; writing—original draft; writing—review and editing; methodology. Christoph Driessen : Writing—review and editing; methodology; conceptualization; writing—original draft. Martin Kaiser : Conceptualization; writing—original draft; writing—review and editing; methodology. Aurore Perrot : Methodology; writing—review and editing; writing—original draft; conceptualization. Ralph Wäsch : Writing—review and editing; methodology; conceptualization; writing—original draft. Charlotte L. B. M. Korst : Conceptualization; writing—original draft; writing—review and editing; methodology. Annemiek Broijl : Conceptualization; writing—original draft; writing—review and editing; methodology. Cyrille Touzeau : Writing—review and editing; writing—original draft; methodology; conceptualization. Salomon Manier : Methodology; writing—review and editing; writing—original draft; conceptualization. Roman Hajek : Conceptualization; writing—original draft; writing—review and editing; methodology. Jelena Bila : Methodology; writing—review and editing; writing—original draft; conceptualization. Guldane C. Seval : Conceptualization; writing—original draft; writing—review and editing; methodology. Michael O'Dwyer : Conceptualization; writing—original draft; writing—review and editing; methodology. Heinz Ludwig : Methodology; writing—review and editing; writing—original draft; conceptualization. Rakesh Popat : Writing—original draft; conceptualization; methodology; writing—review and editing. Pellegrino Musto : Methodology; writing—review and editing; writing—original draft; conceptualization. Paula Rodriguez‐Otero : Conceptualization; writing—original draft; writing—review and editing; methodology. Kwee Yong : Conceptualization; writing—review and editing; methodology. Marin Kortüm : Conceptualization; writing—original draft; writing—review and editing; methodology. Leo Rasche : Conceptualization; writing—original draft; writing—review and editing; methodology. Evangelos Terpos : Conceptualization; writing—original draft; writing—review and editing; methodology. Marc S. Raab : Methodology; writing—review and editing; writing—original draft; conceptualization. Mario Boccadoro : Conceptualization; writing—original draft; writing—review and editing; methodology. Pieter Sonneveld : Methodology; writing—review and editing; writing—original draft; conceptualization. Hermann Einsele : Conceptualization; writing—original draft; writing—review and editing; methodology. All authors contributed equally to the literature search, design and writing of the review.

CONFLICT OF INTEREST STATEMENT

N.W.C.J.v.d.D. has received research support from Janssen Pharmaceuticals, Amgen, Celgene, Novartis, Cellectis, and BMS, and serves on advisory boards for Janssen Pharmaceuticals, Amgen, Celgene, BMS, Sanofi, Takeda, Roche, Novartis, Bayer, Adaptive, Galapagos, Kite Pharma, Merck, Pfizer, AbbVie, and Servier, all paid to the institution. P.Mo. served on advisory boards for and received honoraria from Janssen, Bristol Myers Squibb, Amgen, Takeda, AbbVie, Sanofi, and Pfizer. J.F.S‐M. declares consulting activities from: AbbVie, Amgen, BMS, Celgene, F.Hoffman‐La Roche, GSK, HaemaLogiX, Johnson & Johnson, KaryoPharm, Merck, Novartis, Pfizer, Regeneron, Sanofi‐Aventis, Takeda and SecuraBio. M‐V.M. has served on advisory boards for Amgen, Bristol‐Myers Squibb/Celgene, GlaxoSmithKline, Janssen Cilag, Kite Pharma, Oncopeptides, Pfizer, Roche, Sanofi, and Stemline; and is a speaker bureau member for Janssen Cilag. M.A.D. has received honoraria from participation in advisory boards and satellite symposia from Amgen, Sanofi, Regeneron, Menarini, Takeda, GSK, BMS, Janssen, BeiGene, Swixx, and AstraZeneca. S.Z. has received research support from Janssen Pharmaceuticals and Takeda, and serves on advisory boards for Janssen Pharmaceuticals, BMS, Sanofi, Takeda, Oncopeptides, and GSK, all paid to institution. F.G.: Advisory/Honoraria: Janssen, BMS‐Celgene, Amgen, Sanofi, Takeda, AstraZeneca, Kyte, Pfizer, Roche, AbbVie, and Menarini. M.E.: Advisory support for Amgen, GSK, Janssen, Stemline, Oncopeptides, Pfizer, Sanofi, Takeda, and BMS R.M.: Consulting or Advisory role: Johnson & Johnson, Pfizer, BMS, Amgen, Takeda, Sanofi, and GSK; honoraria: Johnson & Johnson, Pfizer, AbbVie, BMS, Amgen, Takeda, Sanofi, GSK, and Menarini‐Stemline; Travel Support: Pfizer, Johnson & Johnson, and Sanofi. E.Z.: Honoraria and advisory board member from Janssen, Amgen, Sanofi, BMS, Pfizer, Menarini‐Stemline, and Oncopeptides. M.D. has received speaker/consultancy honoraria from Amgen, BMS, GSK, Janssen, Roche, Sanofi, and Stemline. M.B: Advisory board and speakers bureau: Janssen, BMS, Menarini Stemline, Sanofi, Pfizer, Takeda, and GSK. A.S.: Consulting or Advisory role: BMS/Celgene, Janssen, Sanofi, Haemalogix, Antengene, Celltrion, and Pfizer; Research funding: BMS/Celgene, Janssen, Haemalogix, Antengene; Honoraria: BMS/Celgene, Janssen, Sanofi, Haemalogix, Antengene, and Pfizer. F.S.: Consulting or advisory role: GSK, BMS, Janssen, Oncopeptides, Sanofi, Galapagos, Pfizer, and J&J. Honoraria: Amgen, BMS, Takeda, AbbVie, J&J, Sanofi, Pfizer, GSK, Menarini, and Regeneron. C.D.: Consulting role, advisory role or speaker's bureau: BMS, Johnson and Johnson, Amgen, Novartis, and GSK. M.Ka.: Consulting or advisory role: AbbVie, BMS/Celgene, GSK, Janssen, Pfizer, Poolbeg, Regeneron, and Takeda; Research Funding: BMS/Celgene, Janssen; Honoraria: AbbVie, Janssen, and GSK. A.P.: Honoraria, Consulting or Advisory Role: AbbVie, Adaptive, Amgen, BMS, GSK, Janssen, Menarini Stemline, Pfizer, Sanofi, and Takeda. R.W.: consulted/received honoraria from AbbVie, Alexion, Amgen, BMS, Johnson & Johnson, Kite/Gilead, Novartis, Pfizer, Sanofi, and Takeda, and received research funding from Johnson & Johnson and Sanofi. C.L.B.M.K. reports no conflicts of interest. A.B.: Advisory role or speaker's bureau: BMS, Johnson and Johnson, Amgen, and Sanofi; C.T.: Advisory Boards for Amgen, BMS, GSK, J&J, Pfizer, Sanofi, Takeda, and AbbVie; Honoraria from Amgen, BMS, GSK, J&J, Pfizer, Sanofi, Takeda, and AbbVie; Research Funding from GSK and Sanofi; Travel Expenses: J&J, Pfizer, and Sanofi. S.M.: Consultant for AbbVie, Adaptive Biotechnology, Amgen, Celgene/BMS, GlaxoSmithKline, Janssen, Kite, Novartis, Pfizer, Regeneron, Roche, Sanofi, and Takeda. R.H: Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy; BMS: Consultancy, Honoraria, Research Funding; PharmaMar: Consultancy, Honoraria; Novartis: Consultancy, Research Funding. J.B.: Аdvisory role or provided expert testimony: Amgen, Amicus, Johnson & Johnson, Pfizer, and Takeda; and has received honoraria from Amgen, Amicus, Hemofarm, Johnson & Johnson, Pfizer, and Takeda. G.C.S. has consulted or served in advisory boards for Janssen Pharmaceuticals, Menarini, Amgen, Sanofi, Takeda, Novartis, Pfizer, GSK, and Pharminal, and has received honoraria from Janssen Pharmaceuticals, Menarini, Amgen, Sanofi, Takeda, Novartis, Pfizer and BMS; all paid to the institution. M.O'D. reports consultancy for J&J. H.L.: Speaker's bureau or advisory role: Pfizer, Sanofi, Amgen, Janssen, GSK, Oncopeptides. BMS/Celgene, and Takeda; Research funding: Sanofi, and Amgen. C.F.d.L. has served on advisory boards: J&J, BMS, Amgen, Pfizer, Sanofi, BeiGene, GSK, Roche, and Menarini; has received honoraria: Amgen, J&J, BMS, GSK, Sanofi, Pfizer, and BeiGene; and has received research support from BMS, J&J, Amgen, and GSK. He is the principal investigator on trials evaluating the role of cesnicabtagene autoleucel (ARI0002 cells) in patients with multiple myeloma. R.P. consulted and served on advisory boards for Janssen, Sanofi, GSK, and Roche; has received research funding from GSK and Pfizer; has received honoraria from Janssen, Pfizer, GSK, AbbVie, and BMS; has received travel expenses from Janssen and GSK; and is supported by the National Institute for Health and Care Research, University College London Hospitals Biomedical Research Center. P.Mu. reports honoraria for lectures and/or participation in advisory board memberships, with: AbbVie, Alexion, Amgen, Astellas, Astra‐Zeneca, Bei‐Gene, Bristol‐Myers Squibb, Gilead, GlaxoSmithKline, Grifols, Incyte, Johnson & Johnson, Jazz, Novartis, Pfizer, Roche, Sanofi, Sobi, and Takeda. P.R‐O.: consulting or advisory role: BMS, Johnson and Johnson innovative medicines, Sanofi, GSK, Pfizer, Oncopeptides, Menarini Stemline, H3 Biomedicines, and Roche. Speaker Bureau: GSK, BMS, Johnson and Johnson, Pfizer, Sanofi, AbbVie, and Menarini Stemline. Travel Support: Pfizer. Research Funding: Pfizer (institution). K.Y. reports consultancy for Sanofi, Johnson & Johnson, and Pfizer; Speaker fees from Sanofi, Takeda, and Pfizer; Honoraria from Sanofi, Johnson & Johnson, Amgen, Takeda, Pfizer, and BMS; Research funding Sanofi and BMS. M.Ko. has received honoraria from BMS, Sanofi, Novartis, Pfizer, Menarini, J&J, GSK, and AbbVie; and reports consultancy for BMS, Sanofi, Novartis, Pfizer, Menarini, J&J, GSK, and AbbVie. L.R. has received honoraria from Janssen, BMS, Sanofi, Pfizer, Amgen, GSK, Roche, and research support from BMS. E.T.: Advisory Boards for Amgen, AstraZeneca, EUSA Pharma, BMS, GSK, J&J, Menarini/Stemline, Pfizer, Sanofi, Takeda; Honoraria from Amgen, Antengene, AstraZeneca, EUSA Pharma, BMS, Forus, GSK, J&J, Menarini/Stemline, Novartis, Pfizer, Sanofi, Swixx, and Takeda; Research Funding from Amgen, GSK, J&J, Sanofi, and Takeda; Travel Expenses: Takeda. M.S.R.: Consulting or Advisory Role: BMS/Celgene, Janssen, Amgen, Sanofi, GSK, and Novartis; Research Funding: BMS/Celgene, Janssen, and Sanofi; Honoraria: BMS/Celgene, Janssen, Sanofi, and GSK; Travel Support: Janssen, Amgen, and Sanofi. M.B.: Honoraria from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol Myers Squibb, and AbbVie; Advisory Boards for Janssen and GlaxoSmithKline; Research funding from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol Myers Squibb, and Mundipharma. P.S.: Consulting or Advisory Role for BMS/Celgene, Janssen, Sanofi, GSK, and Pfizer; Research funding: BMS/Celgene, Janssen, Karyopharm, Amgen, and Sanofi; Honoraria: BMS/Celgene, Janssen, Sanofi, and GSK. H.E.: Consulting or Advisory Role: BMS/Celgene, Janssen, Amgen, Takeda, Sanofi, GSK, and Novartis; Research Funding: BMS/Celgene, Janssen, Amgen, GSK, and Sanofi; Honoraria: BMS/Celgene, Janssen, Amgen, Takeda, Sanofi, GSK, and Novartis; Travel Support: BMS/Celgene, Janssen, Amgen, Takeda, Novartis, and Sanofi.

FUNDING

This research received no funding.

DATA AVAILABILITY STATEMENT

Data sharing is not applicable to this article, as no datasets were generated or analyzed during the current study.

REFERENCES

1 Berdeja JG , Madduri D , Usmani SZ , et al. Ciltacabtagene autoleucel, a B‐cell maturation antigen‐directed chimeric antigen receptor T‐cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE‐1): a phase 1b/2 open‐label study . Lancet . 2021 ; 398 ( 10297 ): 314 ‐ 324 . 10.1016/s0140-6736(21)00933-8 34175021

2 Martin T , Usmani SZ , Berdeja JG , et al. Ciltacabtagene autoleucel, an anti‐B‐cell maturation antigen chimeric antigen receptor T‐cell therapy, for relapsed/refractory multiple myeloma: CARTITUDE‐1 2‐year follow‐up . J Clin Oncol . 2023 ; 41 ( 6 ): 1265 ‐ 1274 . 10.1200/jco.22.00842 35658469 PMC9937098

3 Lin Y , Martin TG , Usmani SZ , et al. CARTITUDE‐1 final results: phase 1b/2 study of ciltacabtagene autoleucel in heavily pretreated patients with relapsed/refractory multiple myeloma . J Clin Oncol . 2023 ; 41 ( 16_suppl ): 8009 . 10.1200/JCO.2023.41.16_suppl.8009

4 San‐Miguel J , Dhakal B , Yong K , et al. Cilta‐cel or standard care in lenalidomide‐refractory multiple myeloma . N Engl J Med . 2023 ; 389 ( 4 ): 335 ‐ 347 . 10.1056/NEJMoa2303379 37272512

5 Mateos M‐V , San‐Miguel J , Dhakal B , et al. OA‐65 overall survival (OS) with ciltacabtagene autoleucel (Cilta‐cel) versus standard of care (SoC) in lenalidomide (Len)‐refractory multiple myeloma (MM): phase 3 CARTITUDE‐4 study update . Clin Lymphoma Myeloma Leuk . 2024 ; 24 : S290 . 10.1016/S2152-2650(24)02346-2

6 Munshi NC , Anderson Jr. LD , Shah N , et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma . N Engl J Med . 2021 ; 384 ( 8 ): 705 ‐ 716 . 10.1056/NEJMoa2024850 33626253

7 Ailawadhi S , Arnulf B , Patel K , et al. Ide‐cel vs standard regimens in triple‐class‐exposed relapsed and refractory multiple myeloma: updated KarMMa‐3 analyses . Blood . 2024 ; 144 ( 23 ): 2389 ‐ 2401 . 10.1182/blood.2024024582 39197072

8 van de Donk NWCJ , Moreau P , Garfall AL , et al. Long‐term follow‐up from MajesTEC‐1 of teclistamab, a B‐cell maturation antigen (BCMA) x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM) . J Clin Oncol . 2023 ; 41 ( 16_suppl ): 8011 . 10.1200/JCO.2023.41.16_suppl.8011

9 Garfall AL , Nooka AK , van de Donk NWCJ , et al. Long‐term follow‐up from the phase 1/2 MajesTEC‐1 trial of teclistamab in patients with relapsed/refractory multiple myeloma . J Clin Oncol . 2024 ; 42 ( 16_suppl ): 7540 . 10.1200/JCO.2024.42.16_suppl.7540

10 Tomasson MH , Iida S , Niesvizky R , et al. Long‐term survival and safety of elranatamab in patients with relapsed or refractory multiple myeloma: update from the MagnetisMM‐3 study . HemaSphere . 2024 ; 8 ( 7 ): e136 . 10.1002/hem3.136 39055646 PMC11269363

11 Shah MR , Richter J , Lee HC , et al. Linvoseltamab in patients with relapsed/refractory multiple myeloma: longer follow‐up and selected high‐risk subgroup analyses of the linker‐MM1 study . Blood . 2024 ; 144 ( Suppl 1 ): 3369 . 10.1182/blood-2024-199733

12 Chari A , Touzeau C , Schinke C , et al. Safety and activity of talquetamab in patients with relapsed or refractory multiple myeloma (MonumenTAL‐1): a multicentre, open‐label, phase 1‐2 study . Lancet Haematol . 2025 ; 12 ( 4 ): e269 ‐ e281 . 10.1016/s2352-3026(24)00385-5 40090350

13 Hungria V , Robak P , Hus M , et al. Belantamab mafodotin, bortezomib, and dexamethasone for multiple myeloma . N Engl J Med . 2024 ; 391 ( 5 ): 393 ‐ 407 . 10.1056/NEJMoa2405090 38828933

14 Hungria V , Robak P , Hus M , et al. Belantamab mafodotin, bortezomib, and dexamethasone vs daratumumab, bortezomib, and dexamethasone in relapsed/refractory multiple myeloma: overall survival analysis and updated efficacy outcomes of the phase 3 Dreamm‐7 trial . Blood . 2024 ; 144 ( Suppl 1 ): 772 . 10.1182/blood-2024-200336

15 Dimopoulos MA , Beksac M , Pour L , et al. Belantamab mafodotin, pomalidomide, and dexamethasone in multiple myeloma . N Engl J Med . 2024 ; 391 ( 5 ): 408 ‐ 421 . 10.1056/NEJMoa2403407 38828951

16 Rodriguez‐Otero P , Ailawadhi S , Arnulf B , et al. Ide‐cel or standard regimens in relapsed and refractory multiple myeloma . N Engl J Med . 2023 ; 388 ( 11 ): 1002 ‐ 1014 . 10.1056/NEJMoa2213614 36762851

17 Merz M , Albici AM , von Tresckow B , et al. Idecabtagene vicleucel or ciltacabtagene autoleucel for relapsed or refractory multiple myeloma: an international multicenter study . HemaSphere . 2025 ; 9 ( 1 ): e70070 . 10.1002/hem3.70070 39822585 PMC11735948

18 Hansen DK , Peres LC , Dima D , et al. Comparison of standard‐of‐care idecabtagene vicleucel and ciltacabtagene autoleucel in relapsed/refractory multiple myeloma . J Clin Oncol . 2025 ; 43 ( 13 ): 1597 ‐ 1609 . 10.1200/jco-24-01730 39965175 PMC12037312

19 Moreau P , Garfall AL , van de Donk NWCJ , et al. Teclistamab in relapsed or refractory multiple myeloma . N Engl J Med . 2022 ; 387 ( 6 ): 495 ‐ 505 . 10.1056/NEJMoa2203478 35661166 PMC10587778

20 Lesokhin AM , Tomasson MH , Arnulf B , et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM‐3 trial results . Nat Med . 2023 ; 29 ( 9 ): 2259 ‐ 2267 . 10.1038/s41591-023-02528-9 37582952 PMC10504075

21 Richter J , Thomas SK , Krishnan AY , et al. Cevostamab in patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM): updated results from an ongoing phase I study demonstrate clinically meaningful activity and manageable safety and inform the doses and regimen for combination studies . Blood . 2024 ; 144 ( Suppl 1 ): 1021 . 10.1182/blood-2024-199542

22 Bumma N , Richter J , Jagannath S , et al. Linvoseltamab for treatment of relapsed/refractory multiple myeloma . J Clin Oncol . 2024 ; 42 ( 22 ): 2702 ‐ 2712 . 10.1200/jco.24.01008 38879802 PMC11272139

23 Lonial S , Lee HC , Badros A , et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM‐2): a two‐arm, randomised, open‐label, phase 2 study . Lancet Oncol . 2020 ; 21 ( 2 ): 207 ‐ 221 . 10.1016/s1470-2045(19)30788-0 31859245

24 Terpos E , Trudel S , Mateos MV , et al. Practical guidance on clinical management of belantamab mafodotin‐associated ocular events . Am J Hematol . 2025 ; 100 ( 10 ): 1839 ‐ 1850 . 10.1002/ajh.70015 40717676 PMC12417747

25 Dimopoulos MA , Hungria VTM , Radinoff A , et al. Efficacy and safety of single‐agent belantamab mafodotin versus pomalidomide plus low‐dose dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM‐3): a phase 3, open‐label, randomised study . Lancet Haematol . 2023 ; 10 ( 10 ): e801 ‐ e812 . 10.1016/s2352-3026(23)00243-0 37793771

26 Duell J , Leipold AM , Appenzeller S , et al. Sequential antigen loss and branching evolution in lymphoma after CD19‐ and CD20‐targeted T‐cell‐redirecting therapy . Blood . 2024 ; 143 ( 8 ): 685 ‐ 696 . 10.1182/blood.2023021672 37976456 PMC10900140

27 Lee H , Ahn S , Maity R , et al. Mechanisms of antigen escape from BCMA‐ or GPRC5D‐targeted immunotherapies in multiple myeloma . Nat Med . 2023 ; 29 ( 9 ): 2295 ‐ 2306 . 10.1038/s41591-023-02491-5 37653344 PMC10504087

28 Topp MS , Duell J , Zugmaier G , et al. Anti‐B‐cell maturation antigen BiTE molecule AMG 420 induces responses in multiple myeloma . J Clin Oncol . 2020 ; 38 ( 8 ): 775 ‐ 783 . 10.1200/jco.19.02657 31895611

29 Verkleij CPM , O'Neill CA , Broekmans MEC , et al. T‐cell characteristics impact response and resistance to T‐cell‐redirecting bispecific antibodies in multiple myeloma . Clin Cancer Res . 2024 ; 30 ( 14 ): 3006 ‐ 3022 . 10.1158/1078-0432.Ccr-23-3333 38687588

30 Mouhieddine TH , Van Oekelen O , Melnekoff DT , et al. Sequencing T‐cell redirection therapies leads to deep and durable responses in patients with relapsed/refractory myeloma . Blood Adv . 2023 ; 7 ( 6 ): 1056 ‐ 1064 . 10.1182/bloodadvances.2022007923 36018226 PMC10033902

31 Riedhammer C , Bassermann F , Besemer B , et al. Real‐world analysis of teclistamab in 123 RRMM patients from Germany . Leukemia . 2024 ; 38 ( 2 ): 365 ‐ 371 . 10.1038/s41375-024-02154-5 38245601 PMC10844072

32 Nooka AK , Lesokhin AM , Mohty M , et al. Efficacy and safety of elranatamab in patients with relapsed/refractory multiple myeloma (RRMM) and prior B‐cell maturation antigen (BCMA)‐directed therapies: a pooled analysis from MagnetisMM studies . J Clin Oncol . 2023 ; 41 ( 16_suppl ): 8008 . 10.1200/JCO.2023.41.16_suppl.8008

33 Cohen AD , Mateos MV , Cohen YC , et al. Efficacy and safety of cilta‐cel in patients with progressive multiple myeloma after exposure to other BCMA‐targeting agents . Blood . 2023 ; 141 ( 3 ): 219 ‐ 230 . 10.1182/blood.2022015526 36095849 PMC10562529

34 Sidana S , Patel KK , Peres LC , et al. Safety and efficacy of standard‐of‐care ciltacabtagene autoleucel for relapsed/refractory multiple myeloma . Blood . 2025 ; 145 ( 1 ): 85 ‐ 97 . 10.1182/blood.2024025945 39365257 PMC11952008

35 Ferreri CJ , Hildebrandt MAT , Hashmi H , et al. Real‐world experience of patients with multiple myeloma receiving ide‐cel after a prior BCMA‐targeted therapy . Blood Cancer J . 2023 ; 13 ( 1 ): 117 . 10.1038/s41408-023-00886-8 37558706 PMC10412575

36 Sidana S , Ahmed N , Akhtar OS , et al. Standard‐of‐care idecabtagene vicleucel for relapsed/refractory multiple myeloma . Blood . 2025 ; 146 ( 2 ): 167 ‐ 177 . 10.1182/blood.2024026216 40198886

37 Gagelmann N , Dima D , Merz M , et al. Development and validation of a prediction model of outcome after B‐cell maturation antigen‐directed chimeric antigen receptor T‐cell therapy in relapsed/refractory multiple myeloma . J Clin Oncol . 2024 ; 42 ( 14 ): 1665 ‐ 1675 . 10.1200/jco.23.02232 38358946 PMC11095856

38 Ferment B , Lambert J , Caillot D , et al. French early nationwide idecabtagene vicleucel chimeric antigen receptor T‐cell therapy experience in patients with relapsed/refractory multiple myeloma (FENIX): a real‐world IFM study from the DESCAR‐T registry . Br J Haematol . 2024 ; 205 ( 3 ): 990 ‐ 998 . 10.1111/bjh.19505 38747092

39 Hashmi H , Hansen DK , Peres LC , et al. Factors associated with refractoriness or early progression after idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma: US Myeloma Immunotherapy Consortium real world experience . Haematologica . 2020 ; 109 ( 5 ): 1514 ‐ 1524 . 10.3324/haematol.2023.283888 PMC11063864 37855036

40 Afrough A , Hashmi H , Hansen DK , et al. Real‐world impact of bridging therapy on outcomes of ide‐cel for myeloma in the U.S. Myeloma Immunotherapy Consortium . Blood Cancer J . 2024 ; 14 ( 1 ): 63 . 10.1038/s41408-024-00993-0 38609386 PMC11015040

41 Freeman CL , Noble J , Menges M , et al. Tumor burden quantified by soluble B‐cell maturation antigen and metabolic tumor volume determines myeloma CAR‐T outcomes . Blood . 2025 ; 145 ( 15 ): 1645 ‐ 1657 . 10.1182/blood.2024024965 39652773

42 Mohan Lal B , Alzubi M , Alrawabdeh J , et al. Prior exposure to belantamab mafodotin influences outcomes with idecabtagene vicleucel in patients with multiple myeloma . Blood Adv . 2025 ; 9 ( 9 ): 2155 ‐ 2158 . 10.1182/bloodadvances.2024015648 39938011 PMC12051553

43 Magen H , Fried S , Itzhaki O , et al. P889: point‐of‐care anti‐BCMA CAR T‐cell therapy induces encouraging response rates in high‐risk relapse/refractory multiple myeloma . HemaSphere . 2023 ; 7 ( S3 ): e94543ab . 10.1097/01.HS9.0000970460.94543.ab

44 Cowan AJ , Pont MJ , Sather BD , et al. γ‐Secretase inhibitor in combination with BCMA chimeric antigen receptor T‐cell immunotherapy for individuals with relapsed or refractory multiple myeloma: a phase 1, first‐in‐human trial . Lancet Oncol . 2023 ; 24 ( 7 ): 811 ‐ 822 . 10.1016/s1470-2045(23)00246-2 37414012 PMC10783021

45 Firestone RS , Socci ND , Shekarkhand T , et al. Antigen escape as a shared mechanism of resistance to BCMA‐directed therapies in multiple myeloma . Blood . 2024 ; 144 ( 4 ): 402 ‐ 407 . 10.1182/blood.2023023557 38728378 PMC11302451

46 Marvel D , Choudhary G , Song Q , et al. Preclinical analysis of ciltacabtagene autoleucel combination strategies with T cell bispecifics and daratumumab to support optimization of clinical benefit in myeloma patients . Blood . 2024 ; 144 ( Suppl 1 ): 7167 . 10.1182/blood-2024-211334

47 van de Donk NWCJ , Moreau P , San‐Miguel JF , et al. Optimising T‐cell immunotherapy in patients with multiple myeloma: practical considerations from the European Myeloma Network . The Lancet Haematology . 2025 ; 12 ( 8 ): e635 ‐ e649 . 10.1016/s2352-3026(25)00117-6 40580975

48 Touzeau C , Krishnan AY , Moreau P , et al. Efficacy and safety of teclistamab in patients with relapsed/refractory multiple myeloma after BCMA‐targeting therapies . Blood . 2024 ; 144 ( 23 ): 2375 ‐ 2388 . 10.1182/blood.2023023616 39172760

49 Krishnan A , Costa L , Schinke C , et al. P‐023 Talquetamab, a G protein–coupled receptor family C group 5 member D × CD3 bispecific antibody, in relapsed/refractory multiple myeloma: efficacy and safety of patient subgroups from monumenTAL‐1 . Clin Lymphoma Myeloma Leuk . 2023 ; 23 : S45 ‐ S46 . 10.1016/S2152-2650(23)01641-5

50 Dima D , Davis JA , Ahmed N , et al. Safety and efficacy of teclistamab in patients with relapsed/refractory multiple myeloma: a real‐world experience . Transpl Cell Ther . 2024 ; 30 ( 3 ): 308.e1 ‐ 308.e13 . 10.1016/j.jtct.2023.12.016 38151105

51 Reyes KR , Liu YC , Huang CY , et al. Salvage therapies including retreatment with BCMA‐directed approaches after BCMA CAR‐T relapses for multiple myeloma . Blood Adv . 2024 ; 8 ( 9 ): 2207 ‐ 2216 . 10.1182/bloodadvances.2023012066 38429087 PMC11061209

52 Bansal R , De Menezes Silva Corraes A , Brunaldi L , et al. Real world outcome of patients with multiple myeloma who received bispecific antibodies after CAR‐T therapy . J Clin Oncol . 2024 ; 42 ( 16_suppl ): 7520 . 10.1200/JCO.2024.42.16_suppl.7520

53 Dima D , Vazquez‐Martinez MA , Davis JA , et al. Outcomes of Teclistamab (Tec) in patients with Relapsed/Refractory Multiple Myeloma (RRMM) with prior exposure to BCMA‐directed therapy (BCMA‐DT): a multicenter study from the U.S. Multiple Myeloma Immunotherapy Consortium . Blood . 2024 ; 144 ( Suppl 1 ): 897 . 10.1182/blood-2024-203409 PMC12198414 40562770

54 Mohan M , Monge J , Shah N , et al. Teclistamab in relapsed refractory multiple myeloma: multi‐institutional real‐world study . Blood Cancer J . 2024 ; 14 ( 1 ): 35 . 10.1038/s41408-024-01003-z 38443345 PMC10914756

55 Perrot A , Hulin C , Boumendil A , et al. Teclistamab in relapsed refractory multiple myeloma: a multi‐institutional real‐world study from the French early access program . Haematologica . 2025 ; 110 ( 4 ): 990 ‐ 994 . 10.3324/haematol.2024.286118 39568438 PMC11959243

56 Razzo BM , Midha S , Portuguese AJ , et al. Real‐world experience with teclistamab for relapsed/refractory multiple myeloma from the U.S. Myeloma Immunotherapy Consortium . Blood Cancer Discovery . 2025 ; 6 : 561 ‐ 571 . 10.1158/2643-3230.Bcd-24-0354 40629516

57 Hultcrantz M , Derkach A , Hassoun H , et al. Belantamab mafodotin in patients with relapsed/refractory multiple myeloma: a real‐world experience . Blood Neoplasia . 2025 ; 2 ( 3 ): 100103 . 10.1016/j.bneo.2025.100103 40575079 PMC12197964

58 Browning S , Li F , Parker TL , et al. Open‐label, single‐arm phase Ib/II study of immune combination therapy with elotuzumab and belantamab mafodotin in patients with relapsed refractory multiple myeloma . J Clin Oncol . 2024 ; 42 ( 16_suppl ): 7559 . 10.1200/JCO.2024.42.16_suppl.7559

59 Vaxman I , Abeykoon J , Dispenzieri A , et al. “ Real‐life” data of the efficacy and safety of belantamab mafodotin in relapsed multiple myeloma—the Mayo Clinic experience . Blood Cancer J . 2021 ; 11 ( 12 ): 196 . 10.1038/s41408-021-00592-3 34876555 PMC8651684

60 Mi JQ , Zhao W , Jing H , et al. Phase II, open‐label study of ciltacabtagene autoleucel, an anti‐B‐cell maturation antigen chimeric antigen receptor‐T‐cell therapy, in Chinese patients with relapsed/refractory multiple myeloma (CARTIFAN‐1) . J Clin Oncol . 2023 ; 41 ( 6 ): 1275 ‐ 1284 . 10.1200/jco.22.00690 36269898

61 Wang Y , Cao J , Gu W , et al. Long‐term follow‐up of combination of B‐cell maturation antigen and cd19 chimeric antigen receptor T cells in multiple myeloma . J Clin Oncol . 2022 ; 40 ( 20 ): 2246 ‐ 2256 . 10.1200/jco.21.01676 35333600

62 Wang D , Wang J , Hu G , et al. A phase 1 study of a novel fully human BCMA‐targeting CAR (CT103A) in patients with relapsed/refractory multiple myeloma . Blood . 2021 ; 137 ( 21 ): 2890 ‐ 2901 . 10.1182/blood.2020008936 33512480

63 Mobascher P , Engelhardt M , Wäsch R . Successful sequential application of CAR T‐cell‐therapies in relapsed refractory multiple myeloma . Ann Hematol . 2025 ; 104 ( 3 ): 2055 ‐ 2058 . 10.1007/s00277-025-06340-y 40178605 PMC12031839

64 Dholaria B , Kocoglu M , Andrew K , et al. OA‐04 A phase 1 study of P‐BCMA‐ ALLO1, a non‐viral, allogeneic BCMA directed CAR‐T in relapsed/refractory multiple myeloma (RRMM) . Clin Lymphoma Myeloma Leuk . 2024 ; 24 : S3 . 10.1016/S2152-2650(24)01845-7

65 Samur MK , Fulciniti M , Aktas Samur A , et al. Biallelic loss of BCMA as a resistance mechanism to CAR T cell therapy in a patient with multiple myeloma . Nat Commun . 2021 ; 12 ( 1 ): 868 . 10.1038/s41467-021-21177-5 33558511 PMC7870932

66 Da Vià MC , Dietrich O , Truger M , et al. Homozygous BCMA gene deletion in response to anti‐BCMA CAR T cells in a patient with multiple myeloma . Nat Med . 2021 ; 27 ( 4 ): 616 ‐ 619 . 10.1038/s41591-021-01245-5 33619368

67 Ye JC , Schinke C , Touzeau C , et al. P‐098 long‐term efficacy and safety results from the phase 1/2 MonumenTAL‐1 study of talquetamab, a GPRC5D×CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma . Clin Lymphoma Myeloma Leuk . 2024 ; 24 : S99 . 10.1016/S2152-2650(24)02001-9

68 Jakubowiak AJ , Anguille S , Karlin L , et al. Updated results of talquetamab, a GPRC5D×CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma with prior exposure to T‐cell redirecting therapies: results of the phase 1/2 MonumenTAL‐1 study . Blood . 2023 ; 142 ( Suppl 1 ): 3377 . 10.1182/blood-2023-187242

69 Merz M , Dima D , Hashmi H , et al. Bispecific antibodies targeting BCMA or GPRC5D are highly effective in relapsed myeloma after CAR T‐cell therapy . Blood Cancer J . 2024 ; 14 ( 1 ): 214 . 10.1038/s41408-024-01197-2 39632797 PMC11618392

70 Puertas B , Fernández‐Sánchez A , Alejo E , et al. A research center's experience of T‐cell‐redirecting therapies in triple‐class refractory multiple myeloma . Blood Adv . 2024 ; 8 ( 13 ): 3478 ‐ 3487 . 10.1182/bloodadvances.2024012773 38717869 PMC11260841

71 Frenking JH , Riedhammer C , Teipel R , et al. A German multicenter real‐world analysis of talquetamab in 138 patients with relapsed/refractory multiple myeloma . HemaSphere . 2025 ; 9 ( 4 ): e70114 . 10.1002/hem3.70114 40248128 PMC12005056

72 Kumar S , Berdeja J , Sborov D , et al. CEVOSTAMAB in patients with RRMM who are triple‐classrefractory and have received a prior BCMA‐targeted ADC or CAR T‐cell: initial results from the phase I/II CAMMA 2 study . HemaSphere . 2024 ; 8 ( S1 ): 236 ‐ 237 .

73 Delforge M , Richter J , Cohen YC , et al. Biomarker correlates and clinical activity of cevostamab in patients (pts) with triple‐class refractory multiple myeloma (MM) who have received ≥1 prior B‐cell maturation antigen (BCMA)‐targeted bispecific antibody (BsAb): results from the phase I/II CAMMA 2 study . Blood . 2024 ; 144 ( Suppl 1 ): 4732 . 10.1182/blood-2024-199519

74 Cohen AD , Hwang W‐T , Susanibar‐Adaniya S , et al. Sequential T‐cell engagement for myeloma (“STEM”) Trial: a phase 2 study of cevostamab consolidation following BCMA CAR T cell therapy . Blood . 2023 ; 142 ( Suppl 1 ): 3389 . 10.1182/blood-2023-187409

75 Fandrei D , Seiffert S , Rade M , et al. Bispecific antibodies as bridging to BCMA CAR‐T cell therapy for relapsed/refractory multiple myeloma . Blood Cancer Discovery . 2025 ; 6 ( 1 ): 38 ‐ 54 . 10.1158/2643-3230.Bcd-24-0118 39441177 PMC11707513

76 Vucinic V , Fandrei D , Kirchberg J , et al. Cellular composition and clinical factors influencing manufacturing outcomes for anti‐BCMA CAR T cell therapy in a large real‐world cohort of relapsed/refractory multiple myeloma . Blood . 2024 ; 144 ( Suppl 1 ): 2094 . 10.1182/blood-2024-207117

77 Dhakal B , Akhtar OS , Fandrei D , et al. Sequential targeting in multiple myeloma: talquetamab, a GPRC5D bispecific antibody, as a bridge to BCMA CAR‐T therapy . Blood . 2025 ; 146 : 2063 ‐ 2072 . 10.1182/blood.2025029773 40749169

78 Vishwamitra D , Skerget S , Cortes D , et al. Pharmacodynamic signatures and correlatives of response in patients with relapsed/refractory multiple myeloma (RRMM) treated with talquetamab or teclistamab plus daratumumab and pomalidomide . Blood . 2024 ; 144 ( Suppl 1 ): 594 . 10.1182/blood-2024-200300 39115830

79 Friedrich MJ , Neri P , Kehl N , et al. The pre‐existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients . Cancer Cell . 2023 ; 41 ( 4 ): 711 ‐ 725 . 10.1016/j.ccell.2023.02.008 36898378

80 Waldschmidt J , Fandrei D , Vucinic V , et al. Efficacy of anti‐BCMA CAR‐T cell therapies in multiple myeloma patients with prior exposure to bispecific antibodies—results from a retrospective multi‐center registry analysis . Blood . 2024 ; 144 ( Suppl 1 ): 2007 . 10.1182/blood-2024-210451

81 Godby K , Bal S , Giri S , et al. P‐026 combined GPRC5D and BCMA‐targeted T‐cell redirecting therapy in the treatment of RRMM . Clin Lymphoma Myeloma Leuk . 2024 ; 24 : S55 ‐ S56 . 10.1016/S2152-2650(24)01929-3

82 Grajales‐cruz A , Graeter A , Hansen D , et al. P‐027 real world experience of standard of care talquetamab in patients with relapsed and refractory multiple myeloma . Clin Lymphoma Myeloma Leuk . 2024 ; 24 : S56 . 10.1016/S2152-2650(24)01930-X

83 Rejeski K , Hansen DK , Cordas Dos Santos DM , et al. Pre‐apheresis prediction of toxicity and response in patients receiving BCMA‐directed CAR‐T for relapsed/refractory multiple myeloma . Blood . 2024 ; 144 ( Suppl 1 ): 895 . 10.1182/blood-2024-208376 PMC10391746 37525244

84 Rytlewski J , Fuller J , Mertz DR , et al. Correlative analysis to define patient profiles associated with manufacturing and clinical endpoints in relapsed/refractory multiple myeloma (RRMM) patients treated with idecabtagene vicleucel (ide‐cel; bb2121), an anti‐BCMA CAR T cell therapy . J Clin Oncol . 2022 ; 40 ( 16_suppl ): 8021 . 10.1200/JCO.2022.40.16_suppl.8021

85 Einsele H , Rodriguez‐Otero P , Arnulf B , et al. P‐008 Idecabtagene vicleucel (ide‐cel) vs standard regimens in triple‐class–exposed (TCE) relapsed and refractory multiple myeloma (RRMM): KarMMa‐3 subgroup analysis in patients receiving bridging therapy . Clin Lymphoma Myeloma Leuk . 2023 ; 23 : S37 . 10.1016/S2152-2650(23)01626-9

86 Anguille S , Leleu X , Gatt M , et al. P‐005 effectiveness of bridging therapy corresponds to improved outcomes after receiving CAR‐T therapy: phase 3 CARTITUDE‐4 study of patients with relapsed, lenalidomide‐refractory multiple myeloma . Clin Lymphoma Myeloma Leuk . 2024 ; 24 : S42 ‐ S43 . 10.1016/S2152-2650(24)01908-6

87 Sanchez L , Schinke C , Krishnan A , et al. Clinical outcomes of subsequent therapies in patients with relapsed/refractory multiple myeloma following talquetamab treatment: analyses from the phase 1/2 MonumenTAL‐1 study . Blood . 2023 ; 142 ( Suppl 1 ): 2007 . 10.1182/blood-2023-182330

88 Harrison S , Riley CH , Manier S , et al. OA‐05 efficacy of forimtamig, a GPRC5DxCD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): analysis of patient and disease‐related factors associated with responses . Clin Lymphoma Myeloma Leuk . 2023 ; 23 : S3 ‐ S4 . 10.1016/S2152-2650(23)01572-0

89 Trudel S , Cohen AD , Krishnan AY , et al. Cevostamab monotherapy continues to show clinically meaningful activity and manageable safety in patients with heavily pre‐treated relapsed/refractory multiple myeloma (RRMM): updated results from an ongoing phase I study . Blood . 2021 ; 138 ( Suppl 1 ): 157 . 10.1182/blood-2021-147983

90 Aleman A , Kogan Zajdman A , Ghodke‐Puranik Y , et al. Salvage with sequential T cell redirection for myeloma patients who have previously progressed on T cell directed therapy is associated with significant cellular activation of the immune microenvironment . Blood . 2022 ; 140 ( Suppl 1 ): 4193 ‐ 4195 . 10.1182/blood-2022-169538

91 Shekarkhand T , Nemirovsky D , Derkach A , et al. Real‐world analysis of talquetamab in heavily pretreated and high‐risk patients with relapsed/refractory multiple myeloma (RRMM) . HemaSphere . 2025 ; 9 ( S1 ): 3056 ‐ 3057 .

92 Amatangelo M , Flynt E , Stong N , et al. Pharmacodynamic changes in tumor and immune cells drive iberdomide's clinical mechanisms of activity in relapsed and refractory multiple myeloma . Cell Rep Med . 2024 ; 5 ( 6 ): 101571 . 10.1016/j.xcrm.2024.101571 38776914 PMC11228401

93 Bahlis NJ , van de Donk N , Reece D , et al. OA‐01 talquetamab (tal) + daratumumab (dara) + pomalidomide (pom) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): results from the phase 1b TRIMM‐2 study . Clin Lymphoma Myeloma Leuk . 2024 ; 24 : S1 . 10.1016/S2152-2650(24)01842-1

94 Dholaria BR , Weisel K , Mateos M‐V , et al. Talquetamab (tal) + daratumumab (dara) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): updated TRIMM‐2 results . J Clin Oncol . 2023 ; 41 ( 16_suppl ): 8003 . 10.1200/JCO.2023.41.16_suppl.8003

95 Perrot A , Touzeau C , Rodriguez‐Otero P , et al. Talquetamab + cetrelimab in patients with relapsed/refractory multiple myeloma: Initial safety and efficacy results from the phase 1B TRIMM‐3 study . HemaSphere . 2025 ; 9 ( S1 ): 233 ‐ 234 .

96 Paiva B , Gaffney B , Burnett K , et al. Synergistic antitumor activity of alnuctamab (ALNUC; BMS‐986349; CC‐93269), a BCMA 2+1 T cell engager (TCE), and celmod agents in multiple myeloma (MM) preclinical models . Blood . 2022 ; 140 ( Suppl 1 ): 7054 ‐ 7055 . 10.1182/blood-2022-157987

97 Olson K , DiLillo D , Sineshchekova O , et al. A CD38xCD28 costimulatory bispecific antibody demonstrates potent preclinical combinatorial activity with a BCMAxCD3 T cell‐engager . Blood . 2024 ; 144 ( Suppl 1 ): 3283 . 10.1182/blood-2024-194830

98 Hungria V , Hus M , Zherebtsova V , et al. DREAMM‐7 study of belantamab mafodotin + bortezomib + dexamethasone vs daratumumab + bortezomib + dexamethasone in relapsed/refractory multiple myeloma: efficacy in paytients by subsequent therapy . HemaSphere . 2025 ; 9 ( S1 ): 2982 ‐ 2983 .

99 Mailankody S , Devlin SM , Landa J , et al. GPRC5D‐targeted CAR T cells for myeloma . N Engl J Med . 2022 ; 387 ( 13 ): 1196 ‐ 1206 . 10.1056/NEJMoa2209900 36170501 PMC10309537

100 Bal S , Htut M , Nadeem O , et al. BMS‐986393 (CC‐95266), a G protein‐coupled receptor class C group 5 member D (GPRC5D)‐targeted chimeric antigen receptor (CAR) T‐cell therapy for relapsed/refractory multiple myeloma (RRMM): updated results from a phase 1 study . Blood . 2023 ; 142 ( Suppl 1 ): 219 . 10.1182/blood-2023-181857

101 Zhang M , Wei G , Zhou L , et al. GPRC5D CAR T cells (OriCAR‐017) in patients with relapsed or refractory multiple myeloma (POLARIS): a first‐in‐human, single‐centre, single‐arm, phase 1 trial . Lancet Haematol . 2023 ; 10 ( 2 ): e107 ‐ e116 . 10.1016/s2352-3026(22)00372-6 36725117

102 Xia J , Li H , Yan Z , et al. Anti‐G protein‐coupled receptor, class C group 5 member D chimeric antigen receptor T cells in patients with relapsed or refractory multiple myeloma: a single‐arm, phase Ⅱ trial . J Clin Oncol . 2023 ; 41 ( 14 ): 2583 ‐ 2593 . 10.1200/jco.22.01824 36881785 PMC10414745

103 Huang H , Hu Y , Zhang M , et al. Phase I open‐label single‐arm study of GPRC5D CAR T‐cells (OriCAR‐017) in patients with relapsed/refractory multiple myeloma (POLARIS) . J Clin Oncol . 2022 ; 40 ( 16_suppl ): 8004 . 10.1200/JCO.2022.40.16_suppl.8004

104 Jurgens EM , Firestone RS , Chaudhari J , et al. Phase I trial of MCARH109, a G protein‐coupled receptor class C group 5 member D (GPRC5D)‐targeted chimeric antigen receptor T‐cell therapy for multiple myeloma: an updated analysis . J Clin Oncol . 2025 ; 43 ( 5 ): 498 ‐ 504 . 10.1200/jco-24-01785 39631041 PMC11798713

105 Bal S , Anderson Jr. LD , Nadeem O , et al. Efficacy and safety with extended follow‐up in a phase 1 study of BMS‐986393, a G protein‐coupled receptor class C group 5 member D (GPRC5D)‐targeted CAR T cell therapy, in patients (pts) with heavily pretreated relapsed/refractory (RR) multiple myeloma (MM) . Blood . 2024 ; 144 ( Suppl 1 ): 922 . 10.1182/blood-2024-201356 39207810

106 Xia J , Sun Q , Zhou D , et al. Anti‐GPRC5D CAR T‐cell therapy as a salvage treatment in patients with progressive multiple myeloma after anti‐BCMA CAR T‐cell therapy: a single‐centre, single‐arm, phase 2 trial . Lancet Haematol . 2025 ; 12 ( 5 ): e365 ‐ e375 . 10.1016/s2352-3026(25)00048-1 40228504

107 Dimopoulos MA , Terpos E , Boccadoro M , et al. EHA‐EMN evidence‐based guidelines for diagnosis, treatment and follow‐up of patients with multiple myeloma . Nat Rev Clin Oncol . 2025 ; 22 ( 9 ): 680 ‐ 700 . 10.1038/s41571-025-01041-x 40624367

108 Steinhardt MJ , Schaefers C , Leypoldt LB , et al. Activity of CAR‐T cells and bispecific antibodies in multiple myeloma with extramedullary involvement . Blood Cancer J . 2025 ; 15 ( 1 ): 126 . 10.1038/s41408-025-01330-9 40738883 PMC12311153

109 van de Donk NWCJ , Zweegman S . BCMA‐directed therapy for early relapsed and/or refractory multiple myeloma . Nat Rev Clin Oncol . 2024 ; 21 ( 10 ): 707 ‐ 708 . 10.1038/s41571-024-00927-6 39030279

110 Manteca M‐VM , Jakubowiak A , Einsele H , et al. P‐050 talquetamab vs real‐world physician's choice in patients with relapsed/refractory multiple myeloma and prior B‐cell maturation antigen therapy: analyses of monumenTAL‐1 vs LocoMMotion/MoMMent . Clin Lymphoma Myeloma Leuk . 2024 ; 24 : S69 ‐ S70 . 10.1016/S2152-2650(24)01953-0

111 Van Oekelen O , Nath K , Mouhieddine TH , et al. Interventions and outcomes of patients with multiple myeloma receiving salvage therapy after BCMA‐directed CAR T therapy . Blood . 2023 ; 141 ( 7 ): 756 ‐ 765 . 10.1182/blood.2022017848 36327160 PMC10082354

112 van de Donk NWCJ , Chari A , Mateos MV . Mechanisms of resistance against T‐cell engaging bispecific antibodies in multiple myeloma: implications for novel treatment strategies . Lancet Haematol . 2024 ; 11 ( 9 ): e693 ‐ e707 . 10.1016/s2352-3026(24)00186-8 39033769

113 Du J , Fu W‐J , Jiang H , et al. Updated results of a phase I, open‐label study of BCMA/CD19 dual‐targeting fast CAR‐T GC012F for patients with relapsed/refractory multiple myeloma (RRMM) . J Clin Oncol . 2023 ; 41 ( 16_suppl ): 8005 . 10.1200/JCO.2023.41.16_suppl.8005

114 Frigault MJ , Bishop MR , Rosenblatt J , et al. Phase 1 study of CART‐ddBCMA for the treatment of subjects with relapsed and refractory multiple myeloma . Blood Adv . 2023 ; 7 ( 5 ): 768 ‐ 777 . 10.1182/bloodadvances.2022007210 35468618 PMC9989524

115 Zamagni E , Silzle T , Špička I , et al. Phase 3 study of teclistamab (Tec) in combination with lenalidomide (Len) and Tec alone versus Len alone in newly diagnosed multiple myeloma (NDMM) as maintenance therapy following autologous stem cell transplantation (ASCT): safety run‐in (SRI) results from the majestec‐4/EMN30 trial . Blood . 2024 ; 144 ( Suppl 1 ): 494 . 10.1182/blood-2024-205608

116 van de Donk NWCJ , Rasche L , Sidana S , Zweegman S , Garfall AL . T cell‐redirecting bispecific antibodies in multiple myeloma: optimal dosing schedule and duration of treatment . Blood Cancer Discovery . 2024 ; 5 ( 6 ): 388 ‐ 399 . 10.1158/2643-3230.Bcd-24-0124 39321136 PMC11528190

117 Raab MS , Weinhold N , Kortüm KM , et al. Phase 2 study of teclistamab‐based induction regimens in patients with transplant‐eligible (TE) newly diagnosed multiple myeloma (NDMM): results from the GMMG‐HD10/DSMM‐XX (MajesTEC‐5) Trial . Blood . 2024 ; 144 ( Suppl 1 ): 493 . 10.1182/blood-2024-206003

118 van de Donk NWCJ , Vega G , Perrot A , et al. First‐in‐human study of JNJ‐79635322 (JNJ‐5322), a novel, next‐generation trispecific antibody (TsAb), in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Initial phase 1 results . J Clin Oncol . 2025 ; 43 ( 16_suppl ): 7505 . 10.1200/JCO.2025.43.16_suppl.7505

119 Cohen YC , Magen H , Gatt M , et al. Talquetamab plus teclistamab in relapsed or refractory multiple myeloma . N Engl J Med . 2025 ; 392 ( 2 ): 138 ‐ 149 . 10.1056/NEJMoa2406536 39778168

120 Fernández de Larrea C , Staehr M , Lopez AV , et al. Defining an optimal dual‐targeted CAR T‐cell therapy approach simultaneously targeting BCMA and GPRC5D to prevent BCMA escape–driven relapse in multiple myeloma . Blood Cancer Discovery . 2020 ; 1 ( 2 ): 146 ‐ 154 . 10.1158/2643-3230.Bcd-20-0020 33089218 PMC7575057

121 Lichtman EI , Khot A , Augustson B , et al. Phase 1, first‐in‐human study of ISB 2001: a BCMAxCD38xCD3‐targeting trispecific antibody for patients with relapsed/refractory multiple myeloma (RRMM)—dose escalation (DE) results . J Clin Oncol . 2025 ; 43 ( 16_suppl ): 7514 . 10.1200/JCO.2025.43.16_suppl.7514

122 Lim S‐L , Augustson B , Mian HS , et al. A phase I/II study of AZD0305, a novel antibody‐drug conjugate (ADC) targeting GPRC5D, in patients with relapsed/refractory multiple myeloma (RRMM) . Blood . 2024 ; 144 ( Suppl 1 ): 2000.2 . 10.1182/blood-2024-207816