Real-world incidence of severe infections in multiple myeloma patients receiving bispecific antibodies: a meta-analysis.

Introduction

Multiple myeloma (MM) is a malignant plasma cell disorder characterized by clonal proliferation within the bone marrow, leading to end-organ damage and profound immune dysfunction [ 1 ]. Infections are a leading cause of morbidity and mortality from diagnosis throughout the disease course, due to both disease-related immune impairment and treatment-induced immunosuppression [ 2 ]. Although proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, MM remains incurable, and most patients eventually relapse. For heavily pretreated individuals, bispecific antibodies (BiTEs) are a promising immunotherapy, redirecting cytotoxic T cells against malignant plasma cells via dual antigen targeting [ 3 ].

Currently, several BiTEs are approved for clinical use in relapsed/refractory MM (RRMM): teclistamab, elranatamab and the more recently approved linvoseltamab, all targeting B-cell maturation antigen (BCMA), and talquetamab - which targets the G protein-coupled receptor family C group 5 member D (GPRC5D). In pivotal trials, these agents achieved deep and durable responses in patients with limited options. In the phase 1/2 MajesTEC-1 study, teclistamab produced response rates > 60%, with grade 3–4 infections in up to 44.8% at 14 months’ median follow-up [ 4 ]. In the phase 2 MagnetisMM-3 trial, elranatamab showed comparable efficacy, with 39.8% grade 3–4 infections at 14.7 months [ 5 ]. In MonumenTAL-1, talquetamab was associated with infections in 56–76% of patients, and grade 3–4 events in 18–26%, depending on regimen and prior T-cell-redirecting therapy [ 6 ]. Real-world evidence remains heterogeneous across these agents and is currently most mature for teclistamab and talquetamab, for which larger retrospective cohorts and longer clinical experience are available.

BiTEs demonstrate strong efficacy but are associated with a substantial infectious risk, particularly in the context of disease-related immune dysfunction and treatment-induced immunosuppression [ 7 ]. Variability in infection rates and follow-up across studies limits direct comparisons and may underestimate the true burden.

Despite their growing clinical use, a comprehensive quantitative synthesis of real-world grade 3–4 infection rates with BiTEs is lacking. Available retrospective studies report heterogeneous findings in small cohorts. Therefore, this meta-analysis was focused on teclistamab and talquetamab, as they represent the only BiTEs for which the quantity and quality of available real-world evidence allow a robust quantitative synthesis.

Methods

Search strategy and selection criteria

This systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [ 8 ]. The study protocol is registered in PROSPERO (registration ID: CRD420251231632). We searched MEDLINE and LILACS databases from inception (no backwards time limit) to October 1st, 2025, to identify studies evaluating the rate of severe infections in MM patients treated with BiTEs. The complete list of search terms is detailed in Fig. 1 .

Fig. 1 Flow diagram of research screening. Medline: ((((multiple myeloma[Title/Abstract]) OR (myeloma[Title/Abstract])) AND (((((bispecific[Title/Abstract]) OR (bites[Title/Abstract])) OR (teclistamab[Title/Abstract])) OR (elranatamab[Title/Abstract])) OR (talquetamab[Title/Abstract])) AND ((infection*[Text Word]) OR (sepsis[Text Word]))) NOT (review[Publication Type])) NOT (lymphoma[Title]). #1 Multiple myeloma [Ti/Ab] OR myeloma [Ti/Ab] - #2 bispecific [Ti/Ab] OR bites [Ti/Ab] OR teclistamab [Ti/Ab] OR elranatamab [Ti/Ab] OR talquetamab [Ti/Ab] - #3 infection [TW] OR sepsis [TW] - #4 review [PT] - #5 lymphoma [Ti]. #1 AND #2 AND #3 NOT #4 NOT #5. LILACS: ((“multiple myeloma” OR myeloma) AND (bites OR “bispecific”)) AND (“infection”) NOT review

Studies were included if they met the following criteria: (1) retrospective design; (2) enrolled adult patients with MM receiving BiTEs therapy; (3) clearly specified the individual BiTEs agent administered (e.g., teclistamab or talquetamab); and (4) reported the number of patients who developed grade 3–4 infections. Studies lacking sufficient data for outcome extraction were excluded.

No restrictions were applied regarding publication date. In addition, the reference lists of included studies were manually screened to identify further relevant reports. Currently, most available real-world evidence on BiTEs therapy in MM derives from retrospective analyses; therefore, limiting inclusion to this study design minimized heterogeneity related to data collection methods and outcome assessment.

Data collection process

Titles and abstracts were initially screened, followed by full-text review, data extraction, and independent assessment of study quality and risk of bias by two reviewers (FS and AGS) using the web-based platform Rayyan [ 9 ]. Discrepancies were resolved by consensus. For each eligible study, data were collected on study design and characteristics, clinical setting, inclusion criteria, patient population, intervention type, and reported outcomes.

Outcomes

The primary outcome of interest was the proportion of patients who developed grade 3–4 infections during treatment with BiTEs [ 10 ]. Given that all included studies reported the number of infection events relative to the total number of treated patients, data were synthesized as pooled proportions (event rates) rather than comparative effect measures.

Data analysis and risk of bias assessment

All statistical analyses were conducted using R software (version 4.3.1) [ 11 ]. A two-sided p-value < 0.05 was considered indicative of statistical significance. Between-study heterogeneity ( I 2 ) was assessed using the I ² statistic [ 12 ]. A random-effects meta-analysis model was applied to estimate the pooled event rate and its 95% confidence interval (CI).

The summary of findings tables was created through the GRADEpro GDT software (available at gradepro.org ). To assess the study quality, we applied the Quality Appraisal of Case Series Studies Checklist developed by the Institute of Health Economics (IHE) (accessible at http://www.ihe.ca/research-programs/rmd/cssqac/cssqac-about ) . Responses were categorized as “yes,” “unclear/partial,” or “no.” Studies were deemed of acceptable quality (low to moderate risk of bias) if ≥ 70% of responses were “yes” [ 13 ].

Publication bias was evaluated through funnel plots visual inspection [ 14 ]. The quality of evidence was assessed using the GRADE approach [ 15 ].

Meta-regression analyses were conducted to explore potential sources of heterogeneity and to examine whether study-level characteristics influenced the proportion of severe (grade 3–4) infections. The following moderators were evaluated: median treatment duration (months), patient age, sex distribution, previous autologous stem cell transplantation (ASCT), percentage of extramedullary disease (EMD), high cytogenetic risk, International Staging System (ISS) stage I and III, prior exposure to BCMA-directed therapy, penta-refractory status, and use of immunoglobulin supplementation.

Robustness was assessed using leave-one-out analysis. Between-study heterogeneity was tested using the 𝝌² test and reported according to the I² statistic [ 16 ].

Results

Study selection

The bibliographic search yielded 170 records. After the initial screening and triage process, 10 articles met the inclusion criteria and were included in the meta-analysis (Fig. 1 ).

Quality assessment and risk of bias

The overall quality for all outcomes was deemed acceptable (low risk of bias) in most studies. All 10 studies (100%) reported ≥ 70% “yes” responses according to the critical appraisal tool adopted (S-Table 1 ). The overall certainty of the evidence for the severe infection rate outcome was judged to be low (S-Table 2 ).

Studies’ and patients’ characteristics

Table 1 summarizes the 10 studies included in the analysis. All studies had a retrospective design, and 9 out of 10 were multicenter. Three studies reported data stratified by subgroups. Specifically, Mian et al. [ 17 ] classified patients as fit (“Mian fit”) or frail (“Mian frail”); Stork et al. [ 18 ] divided patients into those receiving teclistamab every other week (“Stork nwd”) and those on a weekly dosing schedule (“Stork wd”); and Hammons et al. [ 19 ] distinguished between patients treated with talquetamab in combination with daratumumab and/or pomalidomide (“Hammons comb”) and those receiving talquetamab monotherapy (“Hammons mono”). For the study by Cani et al. [ 20 ], only the cohort of patients treated with talquetamab was included in the analysis, as the group described as receiving BCMA-targeted therapy did not clearly specify the individual agent administered.

Table 1 Studies’ characteristics at baseline Study, year Study type Treatment Patients at baseline, n ° Treatment duration, months (median) Mohan, 2024 R, MC teclistamab 110 3.5 Riedhammer, 2024 R, MC teclistamab 123 6 Mian fit, 2025 R, MC teclistamab 22 13.1 Mian frail, 2025 59 Razzo, 2025 R, MC teclistamab 509 10.1 Stork nwd, 2025 R, MC teclistamab 18 5.9 Stork wd, 2025 55 4.7 Tan, 2025 R, MC teclistamab 210 5.3 Yi, 2025 R, MC teclistamab 42 16.4 Hammons comb, 2023 R, MC talquetamab 15 5.6 Hammons mono, 2023 15 7.4 Frenking, 2024 R, MC talquetamab 138 7.8 Cani, 2025 R, SC talquetamab 57 4.5 Total 1 , 373 8.3 * Comb , combination therapy; MC , multicenter; mono , monotherapy; ndw , non-weekly dosing; SC , single center; wd , weekly dosing * Value represents the weighted mean of the medians reported in individual studies, weighted by the number of patients in each trial § The denominator does not include patients that were not assessed for that clinical manifestation

Seven studies reported data on patients treated with teclistamab, while the remaining three focused on talquetamab [ 17 – 26 ].

The baseline patient population included 1,373 individuals. The sample size of the studies varied, ranging from 15 to 509 patients. Median treatment duration ranged from 3.5 to 16.4 months, with a weighted median duration of 8.3 months (Table 1 ). Females were 584 (42.9%), with a mean age of 67.9 years (Table 2 ). The overall mean number of prior lines of therapy across studies was 6.1. The pooled proportion of patients with prior autologous stem cell transplantation was 82%, while 34% presented with extramedullary disease. The prevalence of high-risk cytogenetic abnormalities was 48%, and 29.7% of patients were classified as ISS stage III (36.3% of patients were ISS stage I). Prior exposure to BCMA-directed therapy was observed in 51.7% of patients, and 51.7% were penta-refractory (Table 2 ).

Table 2 Patient’s characteristics at baseline Study, year n ° patients Age, mean Female, n ° (%) n ° previous line of treatment, mean Previous ASCT, % EMD, % High cytogenetic risk, % ISS III, % ISS I, % BCMA exposed, % Penta-refractory, % Mohan, 2024 110 67.5 54 (49) 6,2 87 44 62* n.a. n.a. 35 76 Riedhammer, 2024 123 66.4 53 (43.1) 6.2 n.a. 36.1* 36.8* 33.7 27.1 37.4 60.2 Mian fit, 2025 22 73.1 9 (40.9) 7.2 n.a. n.a. 61.1 27.3 27.3 50 40 Mian frail, 2025 59 78.4 35 (40.7) 6 n.a. n.a. 55.3 33.3 28.1 33.9 48.2 Razzo, 2025 509 67.8 234 (46) 6.1 65 45* 54 n.a. n.a. 46.4 38 Stork nwd, 2025 18 68.1 10 (55.6) 4.6 n.a. 11.1 28.6* 33.3 27.8 5.6 55.6 Stork wd, 2025 55 65.5 27 (49.1) 5.5 n.a. 29.1 48.9* 23.6 30.9 14.5 88.9 Tan, 2025 210 66.7 93 (44.3) 6.3 n.a. 29.4* 50* 30.6 37.9 43.8 44.1 Yi, 2025 42 66.8 15 (35.7) 6.1 55’ 28.4 41.5 n.a. n.a. 7.1 19 Hammons comb, 2023 15 64.1 5 (33) 6 93 n.a. n.a. n.a. n.a. n.a. n.a. Hammons mono, 2023 15 69.8 7 (47) 6.3 93 n.a. n.a. n.a. n.a. n.a. n.a. Frenking, 2024 138 63.1 42 (30) 6.2 86 48* 48* 43 30 51 47 Cani, 2025 57 64.8 n.a. 6.6 95 n.a. n.a. n.a. n.a. 75 n.a. Total 1 , 373 67.9 584 (42.9) § 6.1 82 § 34 § 48 § 29.7 § 29.9 § 36.3 § 51.7 § ASCT , autologous stem cell transplant; BCMA , B-Cell maturation antigen; EMD , extramedullary disease; ISS , international staging system; n.a. , not available *Percentage is calculated based on total of patients assessed for that clinical manifestation § The denominator does not include patients that were not assessed for that clinical manifestation

Severe infection rate

A total of 339 patients (24.7%) experienced grade 3–4 infections after a weighted median follow-up of 8.3 months, corresponding to a pooled event rate of 0.25 (95% CI, 0.22–0.30) as shown in Fig. 2 A. Moderate heterogeneity was observed (Tau²=0.0030; Chi²=25.45, df = 12, p = 0.0128; I ²=52.9%). In Fig. 2 B, Egger’s test did not indicate significant funnel plot asymmetry (intercept = 1.0, 95% CI, -0.57 to 2.58; p = 0.237). In the subgroup analysis, studies evaluating teclistamab included a total of 1,148 patients, with a pooled event rate of 0.26 (95% CI, 0.22–0.31; I ²=59.3%). Studies assessing talquetamab comprised 225 patients, showing a pooled event rate of 0.23 (95% CI, 0.14–0.33) with moderate heterogeneity ( I ²=48.2%).

Fig. 2 Meta-analysis of grade 3–4 infections in the included studies, funnel plot and meta-regression analysis. A Meta-analysis of patients with multiple myeloma assessing grade 3–4 infection events. Effects are expressed as pooled event rates with 95% confidence intervals (CIs). B Funnel plot under random effect model. Egger’s test did not indicate statistically significant asymmetry (intercept = 1.0, 95% CI: − 0.57 to 2.58, p = 0.237)

Given the observed heterogeneity, meta-regression identified a significant inverse association between severe infection rates and both prior lines of therapy ( p = 0.002) and prior BCMA exposure ( p = 0.0019), as shown in Fig. 3 . Studies including more heavily pretreated or BCMA-exposed patients reported lower infection rates. Indeed, when outlier studies were excluded from the pooled analysis, heterogeneity markedly decreased to 7.5%, with a pooled event rate of 0.24 (95% CI, 0.21–0.26), as shown in S-Figure 1 . Interestingly, when considering the two treatment subgroups, the pooled event rate for teclistamab and talquetamab overlapped: 0.24 (95% CI, 0.21–0.27) and 0.24 (95% CI, 0.18–0.31), respectively.

Fig. 3 Meta-regression analysis for n° of previous line of treatment and percentage of BCMA exposed patients prior BiTES therapy. A Meta-regression analysis for n° of previous lines of treatment (mean) for each study on infection rate (%). B Meta-regression analysis for percentage of BCMA exposed patients for each study on infection rate (%)

Other BiTEs-related adverse events

Across the included studies, the overall incidence of cytokine release syndrome (CRS) of any grade was 55.1%, while immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 9% of patients. The pooled overall response rate (ORR) was 63%, and immunoglobulin supplementation was reported in 56% of cases. Unfortunately, not all studies reported data for every variable (S-Table 3 ).

Discussion

BiTEs have significantly improved outcomes for patients with RRMM, but their expanding real-world use makes infectious safety a key concern. In MM, infection risk is multifactorial, driven by disease-related immune dysfunction, prior therapies, and profound hypogammaglobulinemia induced by T-cell–redirecting agents. Defining severe infection incidence and patterns is essential to optimize supportive care and treatment continuity.

This meta-analysis synthesizes real-world data on grade 3–4 infections in MM patients treated with teclistamab or talquetamab, two of the BiTEs currently approved and those supported by the most mature real-world evidence for clinical use in RRMM. Across 10 retrospective cohorts including 1,373 patients, with a median follow-up of 8.3 months, the pooled event rate was 25%, consistent with the pivotal trials previously reported. Notably, the imbalance between teclistamab and talquetamab studies (7 vs. 3) reflects the current landscape of real-world evidence, which is still evolving and remains more extensive for these agents due to longer clinical experience. Moderate heterogeneity was observed, and no evidence of publication bias was detected. In the subgroup analysis, the pooled event rate for teclistamab was 0.26 (95% CI, 0.22–0.31), while for talquetamab it was 0.23 (95% CI, 0.14–0.33), with comparable heterogeneity, suggesting that severe infections may represent a class-related toxicity of T-cell-redirecting therapies rather than a strictly target-specific effect.

Compared with pivotal trials, our studies estimate lies within the lower reported range. In MajesTEC-1, grade 3–4 infections with teclistamab reached 44.8% at 14 months, while in MonumenTAL-1, talquetamab was associated with 18–26% severe infections [ 4 , 6 ]. While BCMA-directed BiTEs appeared to confer a numerically higher infectious risk in pivotal trials, this difference was not observed in our real-world analysis. Shorter follow-up, clinician-driven patient selection, and prophylactic measures after early BCMA safety signals may have attenuated between-agent differences, and the limited talquetamab sample limits statistical power.

Meta-regression revealed a paradoxical inverse association between infection rates and both number of prior treatment lines and prior BCMA exposure ( p = 0.002 and p = 0.0019, respectively), as shown in Fig. 3 . This likely reflects real-world selection bias: clinicians tend to offer BiTEs to fitter, immunologically stable patients, so more heavily pretreated cohorts may represent resilient individuals. This interpretation is supported by the higher infection rate reported in MajesTEC-1 (about 45%) compared with our pooled analysis, whereas talquetamab rates (24%) were broadly consistent with MonumenTAL-1 (≤ 26%). Notably, only three retrospective studies assessed talquetamab, limiting precision. Biological variability in immune competence and tumor-immune microenvironment may also influence both efficacy and infection susceptibility [ 27 ].

Previous meta-analyses reported similar findings. Wang et al. [ 28 ] found grade ≥ 3 infections in about 30% of patients receiving BiTEs, including both BCMA-targeting agents (e.g., teclistamab, elranatamab, linvoseltamab) and non-BCMA-targeting agents (e.g., talquetamab and cevostamab). Vandenboom et al. [ 29 ] likewise reported a 30% pooled rate with BCMA-targeting BiTEs (e.g., teclistamab and elranatamab). Together, these data reinforce infections as a consistent class effect of T-cell-redirecting therapies.

Limitations must be considered. The included studies were predominantly retrospective real-world analyses, subject to selection bias, incomplete data capture, and reporting variability, thus providing lower-quality evidence than randomized trials. Differences in patient populations, follow-up, and outcome definitions further limit cross-trial comparability. These findings should therefore be considered hypothesis-generating, particularly regarding the apparent similarity in grade 3–4 infection rates. Temporal heterogeneity in infection prevention and supportive care may also have influenced results. Inconsistent reporting of infection prophylaxis limited adjustment for its impact, and the imbalance in studies on teclistamab and talquetamab further restricts comparability.

Standardized tools to assess infection risk - integrated with validated instruments evaluating patient frailty - and prospective registries with harmonized pharmacovigilance are needed to refine prevention strategies and ensure the safe integration of BiTEs into MM care.

In conclusion, this study provides the first real-world estimate of severe infections in RRMM patients treated with approved BiTEs (teclistamab and talquetamab). About 25% developed grade 3–4 infections over 8.3 months of follow-up, confirming that infection remains a major clinical challenge and supporting systematic monitoring and preventive strategies in routine practice.

Supplementary Information

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Supplementary Material 1

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Acknowledgements

The authors thank Drs. Tommasina Perrone, Vanessa Innao, Giulio Giordano and Massimo Martino for technical support and valuable discussions.

Author contributions

F.S. and A.G.S. conceived the project; F.S. and A.G.S. designed the analyses; F.S. and V.D. acquired data; F.S. verified the raw data before analyses and performed pre-processing informatic analysis; F.S. and A.G.S. performed the informatic analysis and interpreted data; F.S., V.D., H.E., A.G.S. contributed with scientific discussions; F.S. and A.G.S. wrote the manuscript, which has been revised by F.D., A.V. and R.R., and approved by all the authors.

Funding

Open access funding provided by Università degli Studi di Bari Aldo Moro within the CRUI-CARE Agreement. This research was funded by the European Union - NextGenerationEU - National Recovery and Resilience Plan (NRRP) – MISSION 4 COMPONENT 2, INVESTMENT N. 1.1, CALL PRIN 2022 PNRR D.D. 1409 14-09-2022 – VISIUMM (project n. 2022ZKKWLW) CUP: H53D23006570006 to AGS; by European Union—Next Generation EU—PNRR M6C2— “Investimento 2.1 Potenziamento e rafforzamento della ricerca biomedica nel SSN” (project n. PNRR-POC-2022-12375862 FUSION-TARGET) to A.G.S.; by the Italian network of excellence for advanced diagnosis (INNOVA), Ministero della Salute (code PNC-E3-2022-23683266 PNC-HLS-DA) to V.D. and A.G.S.; Complementary National Plan PNC-I.1 "Research initiatives for innovative technologies and pathways in the health and welfare sector” D.D. 931 of 06/06/2022, DARE - DigitAl lifelong pRevEntion initiative (code PNC0000002) to A.V. and R.R.; PNRR-MCNT1-2023-12377893 DEMMMO- “Deciphering multiple myeloma using multiomic approaches for immunotherapy modeling“ (CUP: H93C23001080006) to V.D. and A.G.S. This work was also supported by independent research grants from Pfizer to A.G.S. Pfizer had no role in the design, conduct, analysis, or interpretation of the data, nor in the writing of the manuscript (study n. 97499737 SMART-BITE and study n. 101069601 BIS-HUB).

Data availability

Data will be provided by the author upon reasonable request.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

H.E. received honoraria for Bristol-Myers-Squibb, Celgene, Janssen, Amgen, Takeda, Sanofi, GSK, Novartis, Roche, Research Funding (BMS/Celgene, Janssen, Sanofi; GSK, Amgen) Consultancy (Amgen, BMS, Celgene, Janssen, GSK, Novartis, Roche, Sanofi, Takeda); A.V. received speaker honorariums from Pfizer, Sanofi, Bristol Myers Squibb, Takeda, Janssen Cilag, AstraZeneca, Menarini, and Amgen; R.R. has served as a speaker or consultant for Amgen, BMS-Celgene, CSL Behring, Janssen Cilag, Octapharma, Pfizer, Sanofi, Takeda; A.G.S. has received speaker honorariums from Sanofi, Amgen, and AstraZeneca. He has also participated on advisory boards for Pfizer and Menarini. He received travel support for educational purposes from Janssen Cilag. These potential conflicts of interest do not imply bias or influence on the authors’ opinions or actions. The authors are aware of the importance of transparency in the scientific field and are committed to defending their integrity and the trust in them within the scientific community.

References

1. Kyle RA Rajkumar SV Multiple myeloma Blood 2008 111 6 2962 2972 10.1182/blood-2007-10-078022 18332230 PMC2265446 Kyle RA, Rajkumar SV (2008) Multiple myeloma. Blood 111(6):2962–2972 18332230 10.1182/blood-2007-10-078022 PMC2265446

2. Raje NS Anaissie E Kumar SK Consensus guidelines and recommendations for infection prevention in multiple myeloma: a report from the International Myeloma Working Group Lancet Haematol 2022 9 2 e143 e161 10.1016/S2352-3026(21)00283-0 35114152 Raje NS, Anaissie E, Kumar SK et al (2022) Consensus guidelines and recommendations for infection prevention in multiple myeloma: a report from the International Myeloma Working Group. Lancet Haematol 9(2):e143–e161 35114152 10.1016/S2352-3026(21)00283-0

3. Rodriguez-Otero P Usmani S Cohen AD International Myeloma Working Group immunotherapy committee consensus guidelines and recommendations for optimal use of T-cell-engaging bispecific antibodies in multiple myeloma Lancet Oncol 2024 25 5 e205 e216 10.1016/S1470-2045(24)00043-3 38697166 Rodriguez-Otero P, Usmani S, Cohen AD et al (2024) International Myeloma Working Group immunotherapy committee consensus guidelines and recommendations for optimal use of T-cell-engaging bispecific antibodies in multiple myeloma. Lancet Oncol 25(5):e205–e216 38697166 10.1016/S1470-2045(24)00043-3

4. Moreau P Garfall AL van de Donk NWCJ Teclistamab in Relapsed or Refractory Multiple Myeloma N Engl J Med 2022 387 6 495 505 10.1056/NEJMoa2203478 35661166 PMC10587778 Moreau P, Garfall AL, van de Donk NWCJ et al (2022) Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med 387(6):495–505 35661166 10.1056/NEJMoa2203478 PMC10587778

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

6. Chari A Minnema MC Berdeja JG Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma N Engl J Med 2022 387 2232 2244 10.1056/NEJMoa2204591 36507686 Chari A, Minnema MC, Berdeja JG et al (2022) Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma. N Engl J Med 387:2232–2244 36507686 10.1056/NEJMoa2204591

7. Jolles S Giralt S Kerre T Lazarus HM Mustafa SS Ria R Vinh DC Agents contributing to secondary immunodeficiency development in patients with multiple myeloma, chronic lymphocytic leukemia and non-Hodgkin lymphoma: A systematic literature review Front Oncol 2023 13 1098326 10.3389/fonc.2023.1098326 36824125 PMC9941665 Jolles S, Giralt S, Kerre T, Lazarus HM, Mustafa SS, Ria R, Vinh DC (2023) Agents contributing to secondary immunodeficiency development in patients with multiple myeloma, chronic lymphocytic leukemia and non-Hodgkin lymphoma: A systematic literature review. Front Oncol 13:1098326 36824125 10.3389/fonc.2023.1098326 PMC9941665

8. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71

9. Ouzzani M Hammady H Fedorowicz Z Rayyan—a web and mobile app for systematic reviews Syst Rev 2016 5 210 10.1186/s13643-016-0384-4 27919275 PMC5139140 Ouzzani M, Hammady H, Fedorowicz Z et al (2016) Rayyan—a web and mobile app for systematic reviews. Syst Rev 5:210 27919275 10.1186/s13643-016-0384-4 PMC5139140

10. Freites-Martinez A Santana N Arias-Santiago S Viera A Using the Common Terminology Criteria for Adverse Events (CTCAE - Version 5.0) to Evaluate the Severity of Adverse Events of Anticancer Therapies Actas Dermosifiliogr (Engl Ed) 2021 112 90 92 10.1016/j.ad.2019.05.009 32891586 Freites-Martinez A, Santana N, Arias-Santiago S, Viera A (2021) Using the Common Terminology Criteria for Adverse Events (CTCAE - Version 5.0) to Evaluate the Severity of Adverse Events of Anticancer Therapies. Actas Dermosifiliogr (Engl Ed) 112:90–92 32891586 10.1016/j.ad.2019.05.009

11. R: A Language and Environment for Statistical Computing (Version 4.3.1). R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org

12. Wang Y DelRocco N Lin L Comparisons of various estimates of the I2 statistic for quantifying between-study heterogeneity in meta-analysis Stat Methods Med Res 2024 33 5 745 764 10.1177/09622802241231496 38502022 PMC11759644 Wang Y, DelRocco N, Lin L (2024) Comparisons of various estimates of the I2 statistic for quantifying between-study heterogeneity in meta-analysis. Stat Methods Med Res 33(5):745–764 38502022 10.1177/09622802241231496 PMC11759644

13. Moga C, Guo B, Schopflocher D et al (2012) Development of a quality appraisal tool for case series studies using a modified Delphi Technique. Institute of Health Economics. https://ihe.ca/document/ihe-quality-appraisal-checklist-for-case-series-studies-with-instructions-for-use/

14. Egger M Davey Smith G Schneider M Bias in meta-analysis detected by a simple, graphical test BMJ 1997 315 7109 629 634 10.1136/bmj.315.7109.629 9310563 PMC2127453 Egger M, Davey Smith G, Schneider M et al (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634 9310563 10.1136/bmj.315.7109.629 PMC2127453

15. Schunemann H, Brożek J, Guyatt G et al (2013) GRADE handbook. Grading of recommendations assessment, development and evaluation. GRADE Working Group. https://gdt.gradepro.org/app/handbook/handbook.html

16. Higgins JPT Thompson SG Quantifying heterogeneity in a meta-analysis Stat Med 2002 21 1539 1558 10.1002/sim.1186 12111919 Higgins JPT, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558 12111919 10.1002/sim.1186

17. Mian H Martin TG Pond GR Outcomes of frailty subgroups of older adults (age ≥ 70) treated with teclistamab: an International Myeloma Foundation immunotherapy database real-world analysis Leukemia 2025 39 5 1252 1255 10.1038/s41375-025-02552-3 40113913 Mian H, Martin TG, Pond GR et al (2025) Outcomes of frailty subgroups of older adults (age ≥ 70) treated with teclistamab: an International Myeloma Foundation immunotherapy database real-world analysis. Leukemia 39(5):1252–1255 40113913 10.1038/s41375-025-02552-3

18. Stork M Radocha J Mihalyova J De-escalated Teclistamab dosing in relapsed/refractory multiple myeloma: Czech myeloma group real-world evidence analysis Ann Hematol 2025 104 8 4141 4147 10.1007/s00277-025-06529-1 40824489 PMC12432020 Stork M, Radocha J, Mihalyova J et al (2025) De-escalated Teclistamab dosing in relapsed/refractory multiple myeloma: Czech myeloma group real-world evidence analysis. Ann Hematol 104(8):4141–4147 40824489 10.1007/s00277-025-06529-1 PMC12432020

19. Hammons L Szabo A Janardan A The changing spectrum of infection with BCMA and GPRC5D targeting bispecific antibody (bsAb) therapy in patients with relapsed refractory multiple myeloma Haematologica 2024 109 3 906 914 10.3324/haematol.2023.283590 37646658 PMC10905074 Hammons L, Szabo A, Janardan A et al (2024) The changing spectrum of infection with BCMA and GPRC5D targeting bispecific antibody (bsAb) therapy in patients with relapsed refractory multiple myeloma. Haematologica 109(3):906–914 37646658 10.3324/haematol.2023.283590 PMC10905074

20. Cani L, Scott SA, Roberts D et al (2025) Infection risk in 158 patients with relapsed/refractory multiple myeloma treated with bispecific antibodies: a single-center experience. Haematologica 111(2):656–664

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

22. Riedhammer C Bassermann F Besemer B Bewarder M Brunner F Carpinteiro A Einsele H Faltin J Frenking J Gezer D Goldman-Mazur S 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 Riedhammer C, Bassermann F, Besemer B, Bewarder M, Brunner F, Carpinteiro A, Einsele H, Faltin J, Frenking J, Gezer D, Goldman-Mazur S et al (2024) Real-world analysis of teclistamab in 123 RRMM patients from Germany. Leukemia 38(2):365–371 38245601 10.1038/s41375-024-02154-5 PMC10844072

23. Razzo BM, Midha S, Portuguese AJ et al (2025) Real-world experience with teclistamab for relapsed/ refractory multiple myeloma from the U.S. Myeloma Immunotherapy Consortium. Blood Cancer Discov 6(6):561–571

24. Tan CR Asoori S Huang CY Real-world evaluation of teclistamab for the treatment of relapsed/refractory multiple myeloma (RRMM): an International Myeloma Working Group Study Blood Cancer J 2025 15 1 53 10.1038/s41408-025-01259-z 40175336 PMC11965530 Tan CR, Asoori S, Huang CY et al (2025) Real-world evaluation of teclistamab for the treatment of relapsed/refractory multiple myeloma (RRMM): an International Myeloma Working Group Study. Blood Cancer J 15(1):53 40175336 10.1038/s41408-025-01259-z PMC11965530

25. Yi JH, Lee JH, Jung SH et al (2025) Real-world efficacy and safety of teclistamab for patients with relapsed or refractory multiple myeloma: nationwide retrospective analysis of the named patient program in Korea. Cancer Res Treat Epub ahead of print. 10.4143/crt.2025.399

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

27. Solimando AG Malerba E Leone P Prete M Terragna C Cavo M Racanelli V Drug resistance in multiple myeloma: Soldiers and weapons in the bone marrow niche Front Oncol 2022 12 973836 10.3389/fonc.2022.973836 36212502 PMC9533079 Solimando AG, Malerba E, Leone P, Prete M, Terragna C, Cavo M, Racanelli V (2022) Drug resistance in multiple myeloma: Soldiers and weapons in the bone marrow niche. Front Oncol 12:973836 36212502 10.3389/fonc.2022.973836 PMC9533079

28. Wang X Zhao A Zhu J Niu T Efficacy and safety of bispecific antibodies therapy for relapsed or refractory multiple myeloma: a systematic review and meta-analysis of prospective clinical trials Front Immunol 2024 15 1348955 10.3389/fimmu.2024.1348955 38482019 PMC10933024 Wang X, Zhao A, Zhu J, Niu T (2024) Efficacy and safety of bispecific antibodies therapy for relapsed or refractory multiple myeloma: a systematic review and meta-analysis of prospective clinical trials. Front Immunol 15:1348955 38482019 10.3389/fimmu.2024.1348955 PMC10933024

29. Vandenboom H, Akhtar O, Szabo A et al (2025) Safety and efficacy of BCMA CAR-T vs. bispecific antibodies in patients with relapsed multiple myeloma: a systematic review and meta-analysis. Haematologica 111(2):745–750