Bispecific antibodies targeting BCMA, GPRC5D, and FcRH5 for multiple myeloma therapy: latest updates from ASCO 2023 Annual Meeting

Several bispecific antibodies (bsAbs) targeting BCMA, GPRC5D, and FcRH5 are in clinical trials for heavily pretreated multiple myeloma (MM) patients. Teclistamab was approved for relapsed/refractory MM therapy in 2022, while elranatamab, linvoseltamab, F182112, talquetamab, and cevostamab are currently undergoing clinical trials. This study summarizes several latest reports on bsAbs for the treatment of MM from the ASCO 2023 Annual Meeting.


Teclistamab
Teclistamab is the first BCMA × CD3 bsAb approved for the treatment of RRMM (Table 1).In the long-term follow-up (FU) from MajesTEC-1 study, 43% of RRMM patients (pts) achieved a complete response (CR) or stringent CR with teclistamab monotherapy (Table 2) [1].Median disease-free survival (mPFS) and overall survival (mOS) were 12.5 months (m) and 21.9 m, respectively.Pts who achieved a partial response (PR) or better in phase 1, or a CR or better in phase 2, are eligible to transition from QW to Q2W.Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 72% and 3% of pts, respectively, and 6 deaths related to treatment were reported.Grade 3/4 neutropenia and lymphopenia occurred in 65% and 33% of pts, respectively.A grade 3/4 infection occurred in 52% of pts.
A retrospective analysis of teclistamab in RRMM pts with prior BCMA and GPRC5D-directed therapies demonstrated an overall response rate (ORR) of 60% (9/15), with an ORR of 50% (5/10) among the subgroup receiving prior BCMA-targeted therapy at a mFU of 1.3 m (Table 2) [2].CRS and neurotoxicity were observed in 41% and 13% of pts, respectively.
In the RedirecTT-1 study, talquetamab was used combined with teclistamab for RRMM treatment (Table 2) [11].ORR was 84% and CR (including ≥ CR) was achieved in 34% of pts at a mFU of 14.4 m.CRS occurred in 81% of pts, and one pt experienced ICANS.Grade 3/4 neutropenia occurred in 75% of pts.
Talquetamab was used in combination with daratumumab for the treatment of RRMM in the TRIMM-2 study [12].In the latest update, ORR and CR (≥ CR) rates were 78% and 45%, respectively, of the 65 pts included.OS rate at 12 m was 93% and mPFS was 19.4 m.The most common AE was CRS (78%), and 5% of pts experienced ICANS.Infections (≥ G3) occurred in 22% of pts.
In summary, the majority of bsAbs for MM are directed toward BCMA, while the bsAbs targeting other antigens, GPRC5D, and FcRH5, are undergoing clinical trials.The approved teclistamab has demonstrated profound and enduring responses in RRMM pts naïve to prior BCMA-directed therapies.Additionally, RRMM pts received prior BCMA-targeted therapy may also benefit from teclistamab.Clinical trials of bsAbs as monotherapy or in combination therapy are currently recruiting pts with RRMM or NDMM.Author contributions YPS and JJZ designed the study.JJZ, QR, and XYL drafted the manuscript and prepared the tables.All authors participated in the process of drafting and revising the manuscript.All authors read and approved the final manuscript.

Funding
The study is supported by the Major Project of Henan Medical Science and Technology Research Plan (SBGJ202101007), China Postdoctoral Science Foundation (Certificate Number: 2023M733240), and the First Affiliated Hospital of Zhengzhou University.
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Table 1
Properties of bispecific antibodies for multiple myeloma