Bispecific antibodies and dual-targeting CAR-T cells for multiple myeloma: latest updates from the 2023 ASCO annual meeting

Bispecific antibodies (BsAbs) and dual-targeted chimeric antigen receptor T (CAR T) cells have been employed in relapsed/refractory multiple myeloma (RRMM) patients over the past few years, as an increasing number of patients were ineffectively treated by ≥ 3 prior lines of therapy. BCMA/CD3 and GPRC5D/CD3 are the most popular combinations. Clinical findings indicated that patients exhibit a greater susceptibility to stronger and more enduring responses. Here, we summarize the latest data from the 2023 ASCO annual meeting on BsAbs targeting BCMA/CD3, GPRC5D/CD3 and BCMA/CD19 CAR T cells. Supplementary Information The online version contains supplementary material available at 10.1186/s40164-023-00436-9.

Elranatamab is another BCMA/CD3 BsAb.It had the longest median follow-up (15 months) among all phase 2 trials of this type of BsAb.In total, 123 patients received elranatamab therapy.Of these, 96.7% and 42.3% of patients were triple class and penta-drug refractory, respectively.The ORR (objective response rate) was 61%, and the duration of response (DOR) at 12 months (mo) was 74.1% [5].
A phase I trial assessing the safety and preliminary efficacy of F182112, a BCMA/CD3 BsAb, was presented at this meeting.Sixteen patients were enrolled in this clinical study.The ORR was 43.8%, and the most common

To the editor
Although the outcome of relapsed/refractory multiple myeloma (RRMM) has significantly improved in recent years, a large proportion of patients treated with immunotherapy relapse [1].However, bispecific antibodies (BsAbs) and dual-targeting chimeric antigen receptor T (CAR T) cells have shown good efficacy and safety in clinical scenarios [2] and can provide strong and durable responses [3].This review summarizes the latest updates from the 2023 ASCO meeting.

Bispecific antibodies
One poster reported the efficacy of the commercial drug teclistamab, the first BCMA/CD3 BsAb that received FDA approval for the treatment of RRMM.All patients were triple class refractory (TCR), 80% were penta-drug Bispecific antibodies and dual-targeting CAR-T cells for multiple myeloma: latest updates from the 2023 ASCO annual meeting Jiangxue Hou 1 , Yufu Li 1 and Quande Lin 1* treatment-related adverse events (AEs) were CRS (81%), which were all Grade 1-2 [7].
Another combination treatment was tal + daratumumab in the TRIMM-2 study.The ORR was 78% and it showed strong and durable responses with an mPFS of 19.4 mo in heavily pretreated RRMM patients.The 12-mo PFS and overall survival (OS) rates were 76% and 93%, respectively.In addition, the safety profile was acceptable [10].
In addition to all of the above trials, Shaji Kumar is conducting research to investigate the efficacy and safety of cevostamab, which targeted FcRH5 and CD3, in TCR RRMM patients in the CAMMA 2 study [11].Relevant patient recruitment is currently in progress, although no empirical data have been obtained at this stage.