Introduction
Multiple myeloma (MM) is a malignant proliferation of plasma cells within the bone marrow, leading to osteolytic lesions, anemia, renal dysfunction, hypercalcemia, and immunosuppression. In the United States, frontline management of newly diagnosed multiple myeloma for transplant-eligible patients typically involves a quadruplet induction regimen, for example, daratumumab, lenalidomide, bortezomib, dexamethasone (Dara-RVD), followed by autologous stem cell transplantation (ASCT) and maintenance therapy with lenalidomide ± daratumumab when deemed appropriate. For transplant-ineligible individuals, triplet or quadruplet regimens incorporating an anti-CD38 monoclonal antibody plus standard therapies are now widely used. Penta-refractory MM, defined as disease refractory to at least two proteasome inhibitors (PIs), two immunomodulatory drugs (IMiDs), and an anti-CD38 monoclonal antibody, poses a substantial challenge, with median overall survival under 12 months.
Current U.S. guidelines recommend use of agents such as bispecific antibodies (BsAbs) and CAR-T cell therapies for patients with relapsed/refractory MM after at least four prior lines of therapy, though use is evolving toward earlier introduction after triplet-refractory disease based on emerging evidence and expert consensus. CAR T-cell therapies, such as ide-cel and cilta-cel, demonstrate deep responses but are limited by manufacturing delays. Bispecific antibodies (BsAbs), by contrast, offer an off-the-shelf immunotherapy that enables rapid deployment, particularly critical for patients with aggressive disease progression. Furthermore, early data suggest that resistance to one BCMA-targeted modality does not preclude response to another, although challenges such as BCMA gene mutations and antigen escape remain.
This review examines the evolving landscape of BsAbs in MM, highlighting mechanisms of action, clinical efficacy, safety considerations, and future directions. Special attention is given to their role in overcoming therapeutic resistance and optimizing treatment strategies in heavily pretreated patients.
Mechanism of action of bispecific antibodies in MM
BsAbs are engineered to simultaneously engage tumor-associated antigens and immune effector cells, predominantly CD3-positive T cells, to promote immune synapse formation and targeted cytotoxicity. In MM, BsAbs most commonly target BCMA or alternative plasma cell antigens such as GPRC5D and FcRH5. (Table 1 ) These antigens are selected for their high expression on malignant plasma cells and limited off-tumor expression, reducing the risk of off-target effects. Table 2 illustrates the timeline of FDA approval for the bispecific antibodies for RRMM.
Table 1
Target antigens of bispecific antibodies in multiple myeloma and their therapeutic implications
Overview of key plasma cell surface antigens targeted by bispecific antibodies in MM, highlighting their expression patterns, mechanisms of T-cell engagement, and clinical relevance
| Target | Expression in MM | Mechanism of Action | Therapeutic Implications |
| BCMA | High on plasma cells | T-cell redirection | Validated target, high efficacy |
| GPRC5D | Plasma cells, limited normal expression | T-cell redirection | Alternative target to overcome BCMA resistance |
| FcRH5 | Broad plasma cell expression | T-cell redirection | Option post-BCMA failure |
Table 2
FDA approval timeline for bispecific antibodies in RRMM
The timeline of regulatory milestones for BsAbs in relapsed/refractory multiple myeloma (RRMM)
| Agent | Target | FDA Approval Date | Indication (Clinical trials) |
| Teclistamab | BCMA x CD3 | October 2022 | Relapsed/Refractory MM after ≥4 prior therapies (MajesTEC-1) |
| Talquetamab | GPRC5D x CD3 | August 2023 | Relapsed/Refractory MM after ≥4 prior therapies (MonumenTAL-1) |
| Elranatamab | BCMA x CD3 | August 2023 | Relapsed/Refractory MM (MagnetisMM-3) |
| Linvoseltamab | BCMA x CD3 | July 2025 | Relapsed/Refractory MM ≥ 3 prior therapies (LINKER-MM1, NCT03761108 ) |
Clinical development of BsAbs in MM
BCMA-targeting bispecific antibodies
The cumulative data from these trials underscore the robust clinical activity of BCMA-targeted BsAbs in heavily pretreated MM populations, with high response rates and meaningful progression-free survival (Table 3 ). Each agent brings distinct characteristics in terms of administration route, CRS incidence, and depth of response, supporting their ongoing investigation and potential positioning in MM treatment paradigms.
Table 3
Summary of Clinical Efficacy of BCMA-Targeting Bispecific Antibodies in RRMM
Summary of clinical trial outcomes for BCMA-directed bispecific antibodies in heavily pretreated relapsed/refractory multiple myeloma (RRMM) including overall response rates (ORR), Complete Response (CR) or better, median duration of response (DoR), progression-free survival (PFS) and overall survival (OS)
| Drug(Trials) | Teclistamab (MajesTEC-1) [ 1 ] | Elranatamab (MagnetisMM-3) [ 2 ] | Linvoseltamab (LINKER-MM1)[ 3 ] | ABBV-383 (ABBV-383-101)[ 4 ] | Alnuctamab (CC-93269)[ 5 ] |
| Patient population | ≥3 prior lines, no prior BCMA; separate post-BCMA cohort | ≥3 prior lines, no prior BCMA | ≥ 3 prior lines, incl. PI, IMiD, anti-CD38 | ≥3 prior lines, incl. PI, IMiD, anti-CD38 | ≥3 prior lines, triple-class and penta-drug exposed |
| Sample size | 165 (main cohort); 40 (post-BCMA) | 123 | 117 | 124 | 73 |
| ORR (%) | 63% (53% in post-BCMA) | 61% | 71% | 68% at ≥40 mg | 69% at 30 mg dose (63% at ≥30 mg) |
| CR or better (%) | 39% | 35% | 49.6% | VGPR or better: 54% at ≥40 mg | MRD negativity: 100% of responders at 30 mg dose |
| Median time to response | 1.2 months | 1.2 months | 1 month | Not reported | 1.2 months (0.9–4.0 months) |
| Median duration of response (DoR) | 18.4 months (14.8 months post-BCMA) | Not mature | 29.4 months | Not reported | Ongoing, responses deepening over time |
| PFS | 11.3 months (4.5 months post-BCMA) | 15-month PFS: 51% overall, 90% if CR+ | 12-month PFS: 70% | Not reported | Median PFS: 10.1 months; not reached at 30 mg dose |
| OS | Est. 18.3 months | Est. 15-month OS: 57% overall, 93% if CR+ | 12-month OS: 75% | Not reported | Not reached |
| Administration | Subcutaneous, step-up dosing | Subcutaneous, step-up dosing | Intravenous, step-up dosing | Intravenous, no step-up dosing | Subcutaneous, step-up dosing |
Teclistamab, a BCMA x CD3 bispecific antibody, has led the field in this class. In the pivotal MajesTEC-1 trial, 165 patients with heavily pretreated RRMM (median of five prior lines) were enrolled, with all having prior exposure to a PI, IMiD, and anti-CD38 antibody. Notably, patients with high-risk cytogenetics and extramedullary disease were included, enhancing the generalizability of the findings. At a median follow-up of 14.1 months, the overall response rate (ORR) was an impressive 63%, with 39% achieving complete response (CR) or better. The depth of response was further highlighted by minimal residual disease (MRD) negativity in 27% of patients. Time to first response was rapid, with a median of 1.2 months, making teclistamab an attractive option for patients with aggressive disease biology [ 1 , 6 , 7 ].
Subgroup analysis revealed that teclistamab retained clinically meaningful activity in patients with prior BCMA-directed therapy. In the dedicated MajesTEC-1 cohort C, which enrolled 40 patients previously exposed to BCMA-targeted agents, prior anti-BCMA therapy included antibody-drug conjugate (belantamab mafodotin) in 29 patients (72.5%), CAR T-cell therapy in 15 (37.5%), and both modalities in 4 (10%). Despite this heavy pretreatment, teclistamab achieved an overall response rate of 52.5%, with 47.5% ≥ VGPR and 30% CR or better, a median duration of response of 14.8 months, PFS 4.5 months, and OS 15.5 months, supporting its efficacy even after prior BCMA exposure [ 7 ].
Elranatamab has similarly shown robust efficacy in the MagnetisMM-3 trial, which included 123 patients with RRMM and no prior BCMA therapy. The ORR was 61%, with 35% achieving CR or better. Remarkably, patients achieving CR or better exhibited a 90% PFS rate at 15 months, underscoring the durability of deep responses. MRD negativity was confirmed in 29 patients, reinforcing the potential of elranatamab to induce sustained remissions [ 2 ]. Safety profiles were favorable, with manageable cytokine release syndrome (CRS) and low neurotoxicity.
Linvoseltamab was evaluated in the LINKER-MM1 trial involving 282 patients with heavily pretreated RRMM. With 117 patients treated with 200 mg, the ORR was 71%, ≥ VGPR 63%, and ≥ CR 49.6%, with a median DoR of 29.4 months and 12-month PFS rate of 70%. Responses occurred rapidly (median 1 month) and deepened over time, including MRD negativity in >90% of evaluated patients [ 3 ].
ABBV-383, administered intravenously without step-up dosing, demonstrated an ORR of 68% at doses ≥40 mg. Of note, 54% of patients achieved VGPR or better, highlighting the depth of response. The absence of step-up dosing simplifies administration, potentially improving patient convenience and compliance [ 4 ].
Alnuctamab (CC-93269), a 2:1 BCMA x CD3 BsAb development has been discontinued, whereas linvoseltamab has now become the fourth FDA-approved bispecific antibody for multiple myeloma. It has generated promising data, particularly at the 30 mg target dose, where the ORR reached 69%. Impressively, all evaluable responders at this dose achieved MRD negativity, suggesting profound disease clearance. The median PFS was not reached at the time of analysis [ 5 ].
The cumulative data from these trials underscore the robust clinical activity of BCMA-targeted BsAbs in heavily pretreated MM populations, with high response rates. Each agent brings distinct characteristics in terms of administration route, CRS incidence, and depth of response, supporting their ongoing investigation and potential positioning in MM treatment paradigms.
GPRC5D-targeting bispecific antibodies
The clinical outcomes of non-BCMA bispecific antibodies are detailed in Table 4 , highlighting agents such as talquetamab and forimtamig, which target GPRC5D. Talquetamab has emerged as the frontrunner in this class. The MonumenTAL-1 trial enrolled patients with a median of five prior lines of therapy, with high-risk features well-represented. [ 8 ] Talquetamab achieved an ORR of 74% with weekly dosing and 73% with biweekly dosing. Notably, patients with prior T-cell redirection therapy, including CAR-T and BsAbs, maintained a respectable ORR of 63%, supporting talquetamab’s role in sequential immunotherapy strategies [ 8 ]. Median PFS was 7.5 months for weekly dosing, extending to 11.9 months with biweekly dosing. Responses were rapid and durable, with deep responses observed across cytogenetic subgroups.
Table 4
Summary of clinical efficacy of non-BCMA bispecific antibodies in RRMM
Summary of key clinical trials evaluating the efficacy of GPRC5D- and FcRH5-targeting bispecific antibodies in heavily pretreated RRMM populations, including those with prior T-cell redirection therapies. Data include overall response rate (ORR), very good partial response rates or better (VGPR or better), duration of response (DoR), and subgroup efficacy highlights
| Agent | Target | Patient Population | ORR (%) | VGPR or Better (%) | Median Duration of Response | Subgroup Efficacy Highlights | Phase | Key Study |
| Talquetamab | GPRC5D x CD3 | Heavily pretreated RRMM, incl. prior T-cell redirection | 74% (QW), 73% (Q2W), 63% (prior T-cell redirection) | ~59% | Not fully matured (14.9 mo follow-up) | High efficacy across high-risk subgroups; prior CAR-T/BsAb: ORR 63% | II | MonumenTAL-1 (Carolina et al. [ 8 ]) |
| Forimtamig (RG6234) | GPRC5D x CD3 | Heavily pretreated RRMM, incl. prior BCMA-targeted and BsAb therapies | 66.7% | 54.2% | 12.2 months | Durable responses; lower responses in prior BCMA-exposed patients | I | BP42233 (Harrison et al. [ 9 ]) |
| Cevostamab | FcRH5 x CD3 | Triple-class refractory, prior BCMA ADC/CAR T therapy | 67% | 38% | Not reported | Higher ORR in prior CAR-T group; BCMA expression noted higher in prior ADC group | I/II | CAMMA-2 (Shaji et al. [ 10 ]) |
Forimtamig (RG6234), another GPRC5D-targeting BsAb, demonstrated an ORR of 66.7% and a VGPR or better rate of 54.2% in the phase 1a BP42233 trial [ 9 ]. The median duration of response was 12.2 months. Importantly, the study included heavily pretreated patients, with over 70% having received ≥4 prior lines of therapy. While responses were slightly attenuated in patients with prior BCMA-targeted exposure, efficacy remained clinically meaningful, underscoring the potential of GPRC5D as an alternative therapeutic target [ 9 ].
FcRH5-targeting bispecific antibodies
FcRH5 is an emerging target in multiple myeloma, offering potential advantages due to its broader expression on plasma cells compared to BCMA and its preserved expression in BCMA-relapsed or refractory settings. Cevostamab, the leading FcRH5 x CD3 bispecific antibody, has demonstrated encouraging clinical activity, particularly in patients with triple-class refractory disease and prior BCMA-targeted therapies.
The CAMMA-2 study evaluated cevostamab in a heavily pretreated RRMM population, with patients receiving a median of six prior lines of therapy. [ 10 ] The trial specifically included patients with prior exposure to BCMA-targeted antibody-drug conjugates (ADCs) and CAR T-cell therapies, addressing a critical unmet need in post-BCMA failure settings. Notably, FcRH5 expression remained stable in these patients, preserving targetability [ 10 ]. Cevostamab achieved an ORR of 67%, with 38% of patients reaching VGPR or better. Importantly, response rates were even higher in the subgroup of patients previously treated with CAR T-cell therapy, emphasizing cevostamab’s potential to overcome immune resistance mechanisms induced by prior treatments. Median duration of response data remains immature; however, early indications suggest durable remissions, especially in patients achieving VGPR or better.
Cevostamab's activity in post-BCMA patients, coupled with its manageable safety profile, positions FcRH5-targeting BsAbs as a promising strategy for patients who have exhausted other immunotherapy avenues. Further studies are warranted to establish optimal sequencing and combination strategies.
Safety profile and toxicity management
The safety profiles of BsAbs in RRMM largely reflect their potent immune activation, with expected class effects such as CRS, immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenias, and infections (Table 5 ). However, distinctions exist among targets and individual agents, informed by trial data. These adverse effects require vigilant monitoring, preemptive mitigation strategies, and adherence to expert consensus guidelines such as those from the European Myeloma Network (EMN) [ 11 ].
Table 5
Detailed safety and toxicity profile of bispecific antibodies in RRMM, highlighting cytokine release syndrome (CRS), ICANS, infections, cytopenias, and agent-specific adverse events
| Agent | CRS Incidence & Grade | ICANS | Infections (Any/Grade ≥3) | Cytopenias | Unique Toxicities | Serious AEs | Notes |
| Teclistamab | 73%, mostly grade 1–2 [ 1 ] | 15%, mostly low grade [ 1 ] | Pneumonia, COVID-19, 15–19% grade ≥3 [ 1 ] | Major contributor to grade 3/4 events [ 1 ] | Injection-site erythema, GI symptoms, fatigue [ 1 ] | Low | Prophylaxis and G-CSF supportive care |
| Elranatamab | 58%, all grade 1–2 [ 2 ] | 3.4%, all grade 1–2 [ 2 ] | 70% any, 40% grade ≥3, 6.5% fatal [ 2 ] | Major contributor to grade 3/4 events [ 2 ] | Peripheral neuropathy (17% motor, 14% sensory) [ 2 ] | High (infections) | Vigilance required |
| Linvoseltamab | 46%, mostly grade 1–2 (1% grade 3)[ 3 ] | 7.7%, all low grade[ 3 ] | 53% any, 34% grade ≥ 3[ 3 ] | Neutropenia 41% (28% grade 3–4); Anemia 37% (20% grade 3–4); Thrombocytopenia 24% (11% grade 3–4)[ 3 ] | Fatigue (37%), diarrhea (28%), decreased appetite (25%)[ 3 ] | High (Infections) | Infections reduced with maintenance schedule |
| ABBV-383 | 57%, mostly low grade [ 4 ] | Low, not specified [ 4 ] | Not specifically reported [ 4 ] | Neutropenia (37%), anemia (29%) [ 4 ] | Fatigue common (30%) [ 4 ] | Not reported | Simplified administration |
| Alnuctamab | 56%, all grade 1–2 [ 5 ] | Rare, grade 1 only [ 5 ] | 62% any, 16% grade ≥3 [ 5 ] | Neutropenia (55%), anemia (47%), thrombocytopenia (37%) [ 5 ] | None reported uniquely | 81% grade ≥3 AEs [ 5 ] | Manageable with step-up dosing |
| Talquetamab | ~75%, mostly grade 1–2 [ 8 ] | ICANS: 11% [ 8 ] | Infections 58–71%, grade ≥3: 16–26% [ 8 ] | Cytopenias common [ 8 ] | Skin/nail toxicity (53–61%), dysgeusia (50–61%) [ 8 ] | 5–8% [ 8 ] | Supportive dermatologic care recommended |
| Forimtamig | ~60%, mostly grade 1–2 [ 9 ] | Rare [ 9 ] | Not detailed, class-consistent [ 9 ] | Cytopenias reported [ 9 ] | None reported uniquely | Manageable AE | No new safety signals |
| Cevostamab | 71%, all grade 1–2 [ 10 ] | Low [ 10 ] | 38% any, 10% grade ≥3 [ 10 ] | Neutropenia, anemia, thrombocytopenia [ 10 ] | None reported uniquely | Serious AEs: 48% (mainly neutropenia) [ 10 ] | Promising safety in pretreated patients |
Cytokine release syndrome (CRS)
CRS is the most common adverse event across BsAbs, typically occurring early in treatment. Teclistamab reported CRS in 73% of patients, mostly grade 1–2 [ 1 ]. CRS occurred in 46% of patients treated with linvoseltamab, primarily grade 1–2, with only 1% grade 3 events and no grade ≥ 4 CRS reported. Talquetamab and cevostamab similarly reported CRS rates around 70–75%, again predominantly low grade [ 8 , 10 ]. Step-up dosing strategies and prophylactic steroids have effectively mitigated severe CRS, contributing to the favorable safety profiles observed across trials.
Neurotoxicity (ICANS)
Neurotoxicity rates with BsAbs have been generally lower than those seen with CAR T-cell therapies. ICANS was reported in 15% of teclistamab-treated patients [ 1 ] and occurred less frequently with linvoseltamab (7.7%) [ 3 ] and elranatamab (3.4%) [ 2 ]. Talquetamab reported ICANS in approximately 11% of patients, all low grade [ 8 ]. Early recognition and management are critical, but overall, neurotoxicity remains uncommon and manageable with BsAbs.
Cytopenias
Hematologic toxicities are prevalent, with high rates of neutropenia, anemia, and thrombocytopenia observed across trials. For instance, teclistamab demonstrated grade 3–4 cytopenias in over 95% of patients [ 1 ], while linvoseltamab reported neutropenia 41% (grade 3–4, 28%), anemia 37% (grade 3–4, 20%), and thrombocytopenia 24% (grade 3–4, 11%) [ 3 ]. Growth factor support and transfusions are commonly employed supportive measures.
Infections
Infection risk is a significant concern, reflecting both treatment-related immunosuppression and underlying disease factors. Elranatamab reported infections in 70% of patients, with 40% being grade 3–4 and a 6.5% fatality rate [ 2 ] while linvoseltamab reported infections in 53% of patients (grade ≥ 3 in 34%), with pneumonia being the most frequent serious infection [ 3 ]. Talquetamab observed infection rates up to 71%, though most were manageable with standard antimicrobial therapy [ 8 ]. Vigilant infection monitoring and prophylaxis remain essential components of BsAb therapy.
Unique toxicities
Non-BCMA BsAbs have displayed unique toxicity profiles. Talquetamab is notably associated with skin and nail changes (affecting up to 61%) and dysgeusia (~50–61%), attributed to GPRC5D expression in epithelial tissues [ 8 ]. Peripheral neuropathy was observed in 31% of elranatamab-treated patients, albeit predominantly low grade [ 2 ].
Overall, BsAbs demonstrate a manageable safety profile with predictable, mostly low-grade toxicities. Early intervention and supportive care are critical, and experience continues to refine mitigation strategies to enhance patient tolerability.
Combination strategies and future directions
Building upon the promising monotherapy data of BsAbs, combination strategies are at the forefront of ongoing research, aiming to enhance efficacy, deepen responses, and extend durability. These evolving approaches are designed to address resistance mechanisms and engage multiple immune pathways simultaneously, offering hope for improved outcomes in both relapsed/refractory and newly diagnosed settings.
A growing number of clinical trials are evaluating BsAbs in combination with standard myeloma therapies and novel agents (Table 6 ). Notably, several trials are exploring BsAbs alongside anti-CD38 antibodies, such as daratumumab, to leverage synergistic immune activation. Trials like MajesTEC-2 , MajesTEC-3 , and MagnetisMM-5 investigate teclistamab or elranatamab in combination with daratumumab, with the goal of enhancing T-cell engagement and potentially overcoming immune escape mechanisms.
Table 6
Ongoing clinical trials exploring combination strategies and future directions with BsAbs in MM
| Trial | Registration Date | NCT Number | Phase | Patient Population | Intervention | Primary Endpoints |
| MajesTEC-2 | January 2021 | NCT04722146 | I | RRMM | Multiple arms of teclistamab combinations (e.g., with daratumumab, pomalidomide, bortezomib) | Incidence and severity of AEs, DLTs |
| MajesTEC-3 | October 2021 | NCT05083169 | III | RRMM | Teclistamab + daratumumab vs daratumumab-based regimens | PFS |
| MajesTEC-9 | October 2022 | NCT05572515 | III | RRMM | Teclistamab vs Pomalidomide + Bortezomib + Dexamethasone or Carfilzomib + Dexamethasone | PFS |
| TRIMM-3 | April 2022 | NCT05338775 | Ib | RRMM | Talquetamab or teclistamab + PD-1 inhibitor | Safety, DLTs |
| RedirecTT-1 | October 2020 | NCT04586426 | Ib/II | RRMM | Teclistamab + talquetamab ± daratumumab | Safety, DLTs, ORR |
| MagnetisMM-5 | August 2021 | NCT05020236 | II/III | RRMM | Elranatamab monotherapy or Elranatamab + Daratumumab vs Daratumumab + Pomalidomide + Dexamethasone | PFS, safety and activity comparisons |
| MonumenTAL-3 | July 2022 | NCT05455320 | III | RRMM (≥1 prior LOT) | Talquetamab + Daratumab ± Pomalidomide vs Daratumumab + Pomalidomide + Dexamethasone | PFS, response rates, MRD negativity, OS, safety |
In the realm of novel immunomodulation, TRIMM-3 and RedirecTT-1 are pioneering the combination of BsAbs with PD-1 inhibitors and dual BsAb regimens. These strategies seek to further amplify immune responses, sustain T-cell activation, and counteract the immunosuppressive tumor microenvironment. To broaden therapeutic backbones, MagnetisMM-5 and MonumenTAL-3 are evaluating alternative combination regimens of elranatamab and talquetamab against established triplet therapies. These trials aim to establish new standards of care for RRMM by enhancing response depth and durability.
Importantly, the field is rapidly advancing toward next-generation constructs, notably trispecific antibodies. One such agent, ISB 2001, exemplifies this innovation. As a first-in-human trispecific antibody, ISB 2001 simultaneously targets BCMA and CD38 on myeloma cells while engaging CD3 on T cells, maximizing immune synapse formation. Early-phase clinical data are encouraging, with a manageable CRS profile up to 1200 mcg/kg, an impressive ORR of 75%, and deep responses including stringent complete responses (sCR) and MRD negativity. Pharmacokinetic analyses demonstrate linear serum exposure with an estimated half-life of at least 10 days, while biomarker studies confirm transient increases in T-cell activation and proliferation markers, supporting its potent mechanism of action. Trispecific antibodies like ISB 2001 represent the next frontier of immune redirection, with the potential to overcome resistance and deliver profound responses in heavily pretreated RRMM patients.
Altogether, these ongoing trials underscore the versatility and expanding role of BsAbs, not only as standalone therapies but as critical components of multidrug regimens poised to reshape the therapeutic landscape of multiple myeloma.
Conclusion
Bispecific antibodies have rapidly emerged as a transformative class of immunotherapy in the management of multiple myeloma, particularly in the relapsed/refractory setting. By harnessing the power of T-cell redirection, BsAbs offer the unique advantage of deep and durable responses, even among patients with heavily pretreated and penta-refractory disease. The expansion to novel targets, such as GPRC5D and FcRH5, further broadens the therapeutic landscape, providing new options for patients with antigen escape or resistance to prior lines of therapy. Integrating BsAbs with anti-CD38 monoclonal antibodies, proteasome inhibitors, immunomodulatory drugs, and PD-1 inhibitors holds the potential to amplify immune responses and overcome treatment resistance.
Perhaps most excitingly, the development of trispecific antibodies such as ISB 2001 represents a significant evolution in immune redirection strategies. By simultaneously engaging BCMA, CD38, and CD3, trispecific constructs promise to deliver even deeper responses and potentially surmount the challenges of tumor heterogeneity and immune escape mechanisms. Ongoing trials are actively investigating the optimal duration and scheduling of bispecific antibody therapy, including fixed-duration approaches aimed at minimizing cumulative toxicity and preserving long-term immune function. However, global disparities in access to novel immunotherapies remain a major challenge, and future initiatives should prioritize equitable availability of bispecific antibodies and CAR-T therapies in resource-limited countries.
Abbreviations
Antibody–drug conjugate
Adverse event
B-cell maturation antigen
Bispecific antibody
Chimeric antigen receptor t-cell
Cluster of differentiation
Cytokine release syndrome
Dose-limiting toxicity
Fc receptor homolog 5
Food and Drug Administration
G protein–coupled receptor family C group 5 member D
Immunomodulatory Drug
Immune effector cell–associated neurotoxicity syndrome
Line of therapy
Multiple myeloma
Minimal residual disease
Newly diagnosed multiple myeloma
Overall response rate
Overall Survival
Programmed death-1
Progression-free survival
Proteasome inhibitor
Once weekly
Once every two weeks
Relapsed/refractory multiple myeloma
Stringent complete Response
T-cell receptor
T-cell engager
Authors’ contribution
S.S wrote the manuscript and prepared all tables.
Funding
The author(s) received no specific funding for the preparation of this manuscript. The research was performed as part of the academic activities of the authors and received no external financial support.
Data availability
No datasets were generated or analysed during the current study.
Declarations
Ethics approval and consent to participate
Not applicable. This manuscript is a narrative review of previously published studies and does not involve any new studies with human participants or animals conducted by the author.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
Data Availability Statement
No datasets were generated or analysed during the current study.