T-cell redirected bispecific antibodies in relapsed and refractory multiple myeloma: A systematic review and meta-analysis.

person Syed Hamza Bin Waqar State University of New York (SUNY) Downstate Health Sciences University, Brooklyn, NY info_outline Syed Hamza Bin Waqar, Razwana Khanam, Mohammad Ebad Ur Rehman, Asmi Chattaraj, Hassam Ali, Faiz Anwer

Authors person Syed Hamza Bin Waqar State University of New York (SUNY) Downstate Health Sciences University, Brooklyn, NY info_outline Syed Hamza Bin Waqar, Razwana Khanam, Mohammad Ebad Ur Rehman, Asmi Chattaraj, Hassam Ali, Faiz Anwer Organizations State University of New York (SUNY) Downstate Health Sciences University, Brooklyn, NY, Baystate Medical Center, Springfield, MA, Rawalpindi Medical University, Rawalpindi, Pakistan, University Pittsburgh Medical Center, Mckeesport, PA, East Carolina University, Greenville, NC, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH Abstract Disclosures Research Funding No funding received Background: Multiple myeloma (MM) is a malignant plasma cell disorder which remains incurable, and in relapsed and refractory treatment, chimeric antigen receptor therapy shows promise. Bispecific antibodies (bsAbs) utilize the exact mechanism by engaging BCMA and other potential tumor-associated antigens on myeloma cells and T-cells. We have conducted a systematic review and meta-analysis to evaluate the efficacy and safety of bsAbs in heavily pretreated MM cohorts. Methods: We searched PubMed, Clinicaltrials.gov, Cochrane, Google Scholar, Embase, and major conferences (oral and poster presentation), with MeSH terms and keywords for “multiple myeloma” or “relapsed refractory multiple myeloma,” AND “bispecific antibody” or “BiTE”. We included all original studies reported in the English language published from inception until January 2022. After primary and secondary screening, eleven clinical trials were included. Pooled analysis was done with the help of random effects model (Freeman-Tukey Double Arcsine Transformation) in OpenMetaAnalyst software. Results: We identified nine phase I and two phase II trials (n=837), with a mean age of 64.5 years. Most cohorts being triple-, quad- or penta-refractory MM. Complete response (CR) or stringent CR (sCR) reported is 12% (95% CI 9-15.3%, I² 16.54%, n=66), very good partial response (VGPR) 14.8% (95% CI 8.3-22.7%, I² 80.57%, n=93) and partial response (PR) 11.8% (95% CI 0.2-3.41%, I² 93.21%, n=26). The overall response rate (ORR) reported is 59.5% (95% CI 44.7-73.5%, I² 90.71%, n=307). Among the most common adverse events anemia is seen in 44.2% (95% CI 38.1-50.4%, I² 17.86%, n=152), neutropenia in 33.8% (95% CI 18.4-51.2%, I² 93.27%, n=179), thrombocytopenia in 32% (95% CI 21.4-43.6%, I² 75.96%, n=113) and cytokine release syndrome in 57.1% (95% CI 45.5-68.4%, I² 85.63%, n=315). Conclusions: Bispecific antibodies have shown promising efficacy in relapsed and refractory MM cohorts with a very well safety profile. Upcoming phase II/III trials are much awaited, along with combination studies of bsAbs with other agents to gauge response. Agent Clinical trial Phase Sample Prior lines of therapy CR/ sCR VGPR PR ORR, % Duration of response, months Median follow up, months Pavuratamab NCT03287908 I 75 6 5 6 6 36 3.8 1.7 REGN5458 NCT03761108 I/II 68 5 13 25 NR 73.3 NR* 2.4 Pacanalotamab NCT02514239 I 42 5 5 1 1 31 NR* NR* Elranatamab NCT03269136 I 58 6 6 7 1 83 NR* 7.5 Teclistamab 1. NCT03145181/ NCT04557098 2. NCT04108195 1. I/II 2. 1b 1. 159 2.33 5 1.16 2.5 1.24 2.10 1. NR 2.18 1.65 2. NR NR* 1.8.2 2.3.6 TNB-383B NCT03933735 I 103 5 16 19 NR 64 NR* NR* RO7297089 NCT04434469 I 21 8 NR 1 NR NR NR* NR* Cevostamab NCT03275103 I 160 6 NR NR NR 54.5 15.6 NR Talquetamab 1. NCT03399799 2. NCT04108195 Ib 1.78 2.23 6 1. NR 2.5 1.NR 2.12 1.NR 2.13 NR NR* NR* NR- not reported NR*- not reached Clinical outcome data with use of bispecific antibodies.