BISPECIFIC ANTIBODIES IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS OF EFFICACY AND SAFETY
- 1Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil
- 2Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil
Abstract
Background: Relapsed/refractory multiple myeloma (RRMM) remains associated with poor prognosis despite recent therapeutic advances. Bispecific antibodies have demonstrated promising antitumor activity in clinical studies; however, a comprehensive synthesis of their efficacy and safety is still needed. This study aimed to perform a systematic review and meta-analysis to evaluate these outcomes. Methods: A systematic review and meta-analysis were conducted in accordance with the PRISMA guidelines. PubMed, Embase, Scopus, and the Cochrane Library were searched, and 21 studies evaluating the efficacy and safety of bispecific antibodies in patients with RRMM were included. Meta-analyses were performed using R software with a random-effects model (REML) to estimate pooled proportions and corresponding 95% confidence intervals (95% CIs). Sensitivity analyses and subgroup analyses according to therapeutic target (BCMA or GPRC5D) were also performed. Results: Bispecific antibodies demonstrated substantial clinical activity in patients with RRMM. The pooled overall response rate (ORR) was 67.7% (95% CI: 63.1–72.0%), with low heterogeneity (I² = 20.5%). The pooled rate of very good partial response or better (≥VGPR) was 58.2% (95% CI: 55.6–60.7%), with no heterogeneity (I² = 0%). The pooled complete response or better (≥CR) rate reached 37.4% (95% CI: 31.4–43.8%), also with no heterogeneity (I² = 0%). These findings indicate consistent and durable antitumor activity across different bispecific antibody platforms. The pooled minimal residual disease (MRD) negativity rate was 31.4% (95% CI: 7.9–71.0%), with substantial heterogeneity (I² = 90.6%). In subgroup analyses, GPRC5D-targeting bispecific antibodies achieved a higher ORR than BCMA-targeting agents (71.7% vs. 65.3%), with a statistically significant difference (p = 0.039). In the BCMA-only analysis, the ORR remained high (65.3%) without heterogeneity (I² = 0%). Regarding safety, the pooled incidence of any-grade cytokine release syndrome (CRS) was 67.5% (95% CI: 53.5–78.9%), with substantial heterogeneity (I² = 87.6%). However, grade ≥3 CRS was uncommon, with a pooled incidence of 1.1% (95% CI: 0.6–2.2%) and no heterogeneity (I² = 0%). The pooled incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) was 6.8% (95% CI: 3.1–14.0%), with moderate heterogeneity (I² = 63.7%), whereas grade ≥3 ICANS remained infrequent (2.0%; 95% CI: 0.5–7.5%; I² = 40.2%). Among severe hematologic adverse events, grade ≥3 neutropenia was the most frequent (41.4%; 95% CI: 24.8–60.2%), followed by grade ≥3 anemia (31.1%; 95% CI: 25.8–37.0%), grade ≥3 infections (28.1%; 95% CI: 17.8–41.4%), and grade ≥3 thrombocytopenia (22.4%; 95% CI: 18.3–27.1%). Heterogeneity was high for neutropenia (I² = 93.2%) and infections (I² = 87.5%), moderate for anemia (I² = 38.2%), and low for thrombocytopenia (I² = 21.0%). Sensitivity analyses confirmed the robustness of the pooled estimates across all efficacy outcomes. Conclusion: Overall, bispecific antibodies demonstrated high efficacy in the treatment of RRMM, with high response rates and a manageable safety profile. Although cytokine release syndrome was common, severe CRS and ICANS were uncommon. These findings support bispecific antibodies as an important therapeutic option for patients with relapsed/refractory multiple myeloma and reinforce their role as a promising immunotherapeutic strategy in this challenging clinical setting.
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BibTeX
@article{almeida2026bispecific,
title = {{BISPECIFIC ANTIBODIES IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS OF EFFICACY AND SAFETY}},
author = {Isadora Medeiros ALMEIDA and Carolina Marsiglia LUCINI and Maria Fernanda Gonçalves Meirelles FERNANDES and Lucas Mariano PINHEIRO and Flávia Penso BERGAMASCHI and Marina Fração PEREIRA and Juliana TESSA and Jalise Wolski Oliveira ROMANOV},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.107847},
url = {https://doi.org/10.1016/j.htct.2026.107847},
note = {CC BY},
}
RIS
TY - JOUR
TI - BISPECIFIC ANTIBODIES IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS OF EFFICACY AND SAFETY
AU - Isadora Medeiros ALMEIDA
AU - Carolina Marsiglia LUCINI
AU - Maria Fernanda Gonçalves Meirelles FERNANDES
AU - Lucas Mariano PINHEIRO
AU - Flávia Penso BERGAMASCHI
AU - Marina Fração PEREIRA
AU - Juliana TESSA
AU - Jalise Wolski Oliveira ROMANOV
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.107847
UR - https://doi.org/10.1016/j.htct.2026.107847
AB - Background: Relapsed/refractory multiple myeloma (RRMM) remains associated with poor prognosis despite recent therapeutic advances. Bispecific antibodies have demonstrated promising antitumor activity in clinical studies; however, a comprehensive synthesis of their efficacy and safety is still needed. This study aimed to perform a systematic review and meta-analysis to evaluate these outcomes. Methods: A systematic review and meta-analysis were conducted in accordance with the PRISMA guidelines. PubMed, Embase, Scopus, and the Cochrane Library were searched, and 21 studies evaluating the efficacy and safety of bispecific antibodies in patients with RRMM were included. Meta-analyses were performed using R software with a random-effects model (REML) to estimate pooled proportions and corresponding 95% confidence intervals (95% CIs). Sensitivity analyses and subgroup analyses according to therapeutic target (BCMA or GPRC5D) were also performed. Results: Bispecific antibodies demonstrated substantial clinical activity in patients with RRMM. The pooled overall response rate (ORR) was 67.7% (95% CI: 63.1–72.0%), with low heterogeneity (I² = 20.5%). The pooled rate of very good partial response or better (≥VGPR) was 58.2% (95% CI: 55.6–60.7%), with no heterogeneity (I² = 0%). The pooled complete response or better (≥CR) rate reached 37.4% (95% CI: 31.4–43.8%), also with no heterogeneity (I² = 0%). These findings indicate consistent and durable antitumor activity across different bispecific antibody platforms. The pooled minimal residual disease (MRD) negativity rate was 31.4% (95% CI: 7.9–71.0%), with substantial heterogeneity (I² = 90.6%). In subgroup analyses, GPRC5D-targeting bispecific antibodies achieved a higher ORR than BCMA-targeting agents (71.7% vs. 65.3%), with a statistically significant difference (p = 0.039). In the BCMA-only analysis, the ORR remained high (65.3%) without heterogeneity (I² = 0%). Regarding safety, the pooled incidence of any-grade cytokine release syndrome (CRS) was 67.5% (95% CI: 53.5–78.9%), with substantial heterogeneity (I² = 87.6%). However, grade ≥3 CRS was uncommon, with a pooled incidence of 1.1% (95% CI: 0.6–2.2%) and no heterogeneity (I² = 0%). The pooled incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) was 6.8% (95% CI: 3.1–14.0%), with moderate heterogeneity (I² = 63.7%), whereas grade ≥3 ICANS remained infrequent (2.0%; 95% CI: 0.5–7.5%; I² = 40.2%). Among severe hematologic adverse events, grade ≥3 neutropenia was the most frequent (41.4%; 95% CI: 24.8–60.2%), followed by grade ≥3 anemia (31.1%; 95% CI: 25.8–37.0%), grade ≥3 infections (28.1%; 95% CI: 17.8–41.4%), and grade ≥3 thrombocytopenia (22.4%; 95% CI: 18.3–27.1%). Heterogeneity was high for neutropenia (I² = 93.2%) and infections (I² = 87.5%), moderate for anemia (I² = 38.2%), and low for thrombocytopenia (I² = 21.0%). Sensitivity analyses confirmed the robustness of the pooled estimates across all efficacy outcomes. Conclusion: Overall, bispecific antibodies demonstrated high efficacy in the treatment of RRMM, with high response rates and a manageable safety profile. Although cytokine release syndrome was common, severe CRS and ICANS were uncommon. These findings support bispecific antibodies as an important therapeutic option for patients with relapsed/refractory multiple myeloma and reinforce their role as a promising immunotherapeutic strategy in this challenging clinical setting.
SN - 2531-1379
SN - 2531-1387
ER -