Recent updates on bispecific T-cell engager (BiTE) antibodies in relapsed and refractory multiple myeloma.

Abstract

e20034 Background: Bispecific T-cell engager (BiTE) antibodies are currently being studied for various hematological malignancies including relapsed and refractory multiple myeloma (RRMM). BiTE antibodies that target CD3 on T cells and antigens GPRC5D, BCMA or FcRH5 on myeloma cells are being studied in RRMM patients (pts). Methods: A comprehensive literature search was done on Pubmed, Embase, and Cochrane. The data presented in various conferences (ASH, ASCO) were also included. Results: Six clinical trials are currently evaluating anti-BCMA, anti CD3 BiTE in RRMM. Madduri et al. reported ORR of 39% in 49 pts treated with REGN5458 an anti BCMA and CD3 BiTE antibody. Grafall et. al reported an ORR of 73% with Teclistamab at 1500µg/kg SC. Harrison et al. reported ORR of 83% in 9 pts treated with 9mg of AMG 701. Lesokhin et al. reported an ORR of 33% among 18 RRMM pts at all dose levels and ORR of 75%. at dose level of 215μg/kg weekly (n=4), and 360 μg/kg weekly (n=4). Rodriguez et al. reported an ORR of 80% among 15 RRMM pts treated with TNB-383B at the dose of 40-60mg IV every 3 weeks. Topp et al reported an ORR of 70% among 10 pts treated with AMG420/BI-836909 at MTD of 400µg/d. Chari et al reported results of Talquetamab which targets GPRC5D which showed an ORR of 66% in 55 evaluable pts. ORR at RP2D (405 µg/kg SC) was 69% in 19 pts treated at this dose. Cohen et al reported results on BFCR4350A, an anti FcRH5 BiTE which showed an ORR of 53% at dose ≥3.6/20mg Q3W. Cytokine release syndrome (CRS) is a serious side effect of BiTE antibodies and was reported in 39%, 64%, 65%, 61%, 45%, 38%, 54% and 76% in studies by Madduri et al, Grafall et al., Harrison et al., Lesokhin et al., Rodriguez et al., Topp et al., Chari et al., and Cohen et al., respectively. Most of the CRS cases were grade 1-2 and resolved either by themselves or required treatment with tocilizumab and steroids. Other most common side effects are reported in table. Conclusions: The most recent data on BiTE antibodies in RRMM has shown promising results with good tolerability. However, the trials are ongoing and a longer follow up is needed.[Table: see text]