Bispecific antibodies targeting BCMA, GPRC5D, and FcRH5 for multiple myeloma therapy: latest updates from ASCO 2023 Annual Meeting
Journal of Hematology & Oncology volume 16, Article number: 92 (2023)
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.
To the editor
The first bispecific antibody (bsAb) for the treatment of relapsed/refractory multiple myeloma (RRMM), teclistamab, has been approved in 2022. Several bsAbs for MM are in clinical trials. We summarized the latest reports on bsAbs for MM therapy from the ASCO 2023 Annual Meeting (ASCO2023).
Updates from clinical studies of BCMA × CD3 bsAbs
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) . 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) . CRS and neurotoxicity were observed in 41% and 13% of pts, respectively.
The MajesTEC-9 study is currently recruiting RRMM pts to compare the efficacy of teclistamab monotherapy versus (vs) pomalidomide + bortezomib + dexamethasone or carfilzomib + dexamethasone .
Elranatamab is a humanized bsAb targeting BCMA and CD3 (Table 1). In the MagnetisMM-3 study, elranatamab monotherapy was administered to 123 pts with RRMM (Table 2) . The objective response and CR rates at a mFU of 12.8 m were 61% and 31.7%, respectively. The duration of response (DoR), PFS and OS at one year were 74.1%, 57.1%, and 62.0%, respectively. SC elranatamab was administered in a stepwise manner, with a target dose of 76 mg QW. Pts who received 6 cycles of treatment and achieved PR lasting more than 2 months were switched to 76 mg Q2W. Grade 3/4 infection included COVID-19 pneumonia (10.6%), pneumonia (7.3%), and sepsis (6.5%).
The MagnetisMM-6 study of elranatamab + daratumumab + lenalidomide vs daratumumab + lenalidomide + dexamethasone in newly diagnosed MM (NDMM) who are ineligible for transplant  and the MagnetisMM-7 study comparing elranatamab vs lenalidomide monotherapy in NDMM following autologous stem cell transplant (ASCT) are actively recruiting participants .
In the LINKER-MM1 study, linvoseltamab monotherapy was administrated to RRMM pts (Table 2) . The ORR was 64% (n = 58) and 50% (n = 104) in the 200 mg and 50 mg cohorts, respectively, at a mFU of 2.3 m and 4.7 m. CRS occurred in 37% (200 mg cohort), and 53% (50 mg cohort) of the pts. ICANS ≥ grade 3 was reported in 2% (200 mg cohort) and 1% (50 mg cohort) of the pts. Infections ≥ grade 3 occurred in 26% (200 mg cohort) and 31% (50 mg cohort) of pts.
F182112 was intravenously administrated to RRMM pts in a phase 1 study (Table 2) . The ORR was 43.8% (7/16), with a mFU of 3.1 m. CRS remained the most common adverse event, occurring in 81% of pts. Grade 3/4 lymphopenia, neutropenia, and leukopenia occurred in 69%, 44%, and 50% of pts, respectively.
Updates on bsAbs targeting GPRC5D or FcRH5 for MM
Talquetamab is a first-in-class G protein-coupled receptor family C group 5 member D (GPRC5D) × CD3 bsAb (Table 1) . In the MonumenTAL-1 study, SC talquetamab was administrated to RRMM pts (Table 2) . The mFU was 14.9 m, 8.6 m, and 11.8 m in cohorts 0.4 mg/kg QW, 0.8 mg/kg Q2W, and prior T-cell redirected therapies, with ORRs of 74%, 73%, and 63%, respectively. CRS and ICANS were observed in 79%, 75%, 77% and 11%, 11%, 3% of pts, respectively. The incidence of grade 3/4 infection was 22%, 16%, and 26%, respectively.
In the RedirecTT-1 study, talquetamab was used combined with teclistamab for RRMM treatment (Table 2) . 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 . 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.
Cevostamab, a bsAb targeting Fc receptor-homolog 5 (FcRH5) and CD3 (Table 1), is being evaluated in RRMM pts who have received prior anti-BCMA therapy, including anti-BCMA antibody-drug conjugates, CAR T cells, and anti-BCMA bsAbs . Subject enrollment is currently in progress.
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.
Availability of data and material
The material supporting the conclusion of this study has been included within the article.
American Society of Clinical Oncology
B-cell maturation antigen
Cytokine release syndrome
G protein-coupled receptor family C group 5 member D
Immune effector cell‐associated neurotoxicity syndrome
Fc receptor-homolog 5
Median duration of response
Overall response rate
- prior T:
Prior T-cell-directed therapies
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Moreau P, Garfall AL, Bhutani M, Oriol A, Nooka AK, Martin TG, Rosiñol L, Mateos M-V, Bahlis NJ, Popat R, Besemer B, Martinez-Lopez J, Krishnan AY, Delforge M, Trancucci D, Verona R, Stephenson T, Chastain K, Sidana S. Long-term follow-up from MajesTEC-1 of teclistamab, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2023;41(16_suppl):8011–8011.
Shekarkhand T, Patel D, Tan CRC, Hultcrantz M, Lesokhin AM, Mailankody S, Hassoun H, Shah UA, Korde N, Maclachlan K, Landau HJ, Scordo M, Chung DJ, Shah GL, Lahoud OB, Giralt S, Usmani SZ. Evaluating the efficacy of commercial teclistamab in relapsed refractory multiple myeloma patients with prior exposure to anti-BCMA therapies. J Clin Oncol. 2023;41(16_suppl):8049–8049.
Hungria VT, Bhutani D, Landgren O, Vieyra D, Guo Y, Verona R, Miao X, Qi M, Watkins L, Shah P, Chastain K, Qi M, Quach H. MajesTEC-9: a randomized phase 3 study of teclistamab versus pomalidomide, bortezomib, and dexamethasone or carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma. J Clin Oncol. 2023;41(16_suppl):8067–8067.
Tomasson MH, Arnulf B, Bahlis NJ, Prince HM, Niesvizky R, Rodríguez-Otero P, Martinez-Lopez J, Koehne G, Jethava Y, Gabayan AE, Stevens DA, Nooka AK, Raje NS, Iida S, Leip E, Conte U, Czibere AG, Viqueira A, Lesokhin AM. Elranatamab, a B-cell maturation antigen (BCMA)-CD3 bispecific antibody, for patients (pts) with relapsed/refractory multiple myeloma (RRMM): extended follow up and biweekly administration from the MagnetisMM-3 study. J Clin Oncol. 2023;41(16_suppl):8039–8039.
Yeh S-P, Huang JSY, Byun JM, DiRienzo C, Viqueira A. MagnetisMM-6: an open-label, multicenter, randomized phase 3 study of elranatamab + daratumumab + lenalidomide (EDR) versus daratumumab + lenalidomide + dexamethasone (DRd) in transplant ineligible (TI) patients with newly diagnosed multiple myeloma (NDMM). J Clin Oncol. 2023;41(16_suppl):TPS065-TPS8065.
Grosicki S, Kim K, Negre E, Vandendries E. MagnetisMM-7: an open-label, multicenter, randomized phase 3 study of elranatamab versus lenalidomide in post-transplant patients with newly diagnosed multiple myeloma. J Clin Oncol. 2023;41(16_suppl):TPS8066–TPS8066.
Bumma N, Richter JR, Dhodapkar MV, Hoffman JE, Suvannasankha A, Zonder JA, Shah MR, Lentzsch S, Maly JJ, Ye JC, Wu KL, DeVeaux M, Chokshi D, Boyapati A, Hazra A, Rodriguez-Lorenc K, Kroog GS, Houvras YJ, Jagannath S. LINKER-MM1 study: linvoseltamab (REGN5458) in patients with relapsed/refractory multiple myeloma. J Clin Oncol. 2023;41(16_suppl):8006–8006.
Qiu L, Wei Y, Jin J, Li X, Liu X, Yin S, Qi J. Results from a first-in-human phase I study of F182112, a B-cell maturation antigen (BCMA)-CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma. J Clin Oncol. 2023;41(16_suppl):8038–8038.
Xia J, Li Z, Xu K. Immunotherapies targeting GPRC5D in relapsed or refractory multiple myeloma: latest updates from 2022 ASH Annual Meeting. J Hematol Oncol. 2023;16(1):60.
Touzeau C, Minnema MC, van de Donk NWCJ, Rodríguez-Otero P, Mateos M-V, Rasche L, Ye JC, Vishwamitra D, Ma X, Qin X, Campagna M, Masterson TJ, Hilder B, Tolbert JA, Renaud T, Goldberg J, Heuck C, Chari A. Pivotal phase 2 MonumenTAL-1 results of talquetamab (tal), a GPRC5DxCD3 bispecific antibody (BsAb), for relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2023;41(16):8036–8036.
Morillo D, Gatt ME, Sebag M, Kim K, Min C-K, Oriol A, Ocio EM, Yoon S-S, Mateos M-V, Chu M, Rodríguez-Otero P, Avivi I, Guo Y, Krevvata M, Peterson MR, Beelen MJ, Vanak J, Banerjee A, Magen H. First results from the Redirectt-1 study with teclistamab (tec) + talquetamab (tal) simultaneously targeting BCMA and GPRC5D in patients (pts) with relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2023;41(16_suppl):8002–8002.
Weisel K, Mateos M-V, Goldschmidt H, Martin TG, Morillo D, Reece DE, Rodríguez-Otero P, Bhutani M, D’Souza A, Oriol A, Rosiñol L, Bahlis NJ, Bakshi K, Kang L, Vandenberk L, Smit M-AD, Wäsch R, van de Donk NWCJ, Chari A. Talquetamab (tal) + daratumumab (dara) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): updated TRIMM-2 results. J Clin Oncol. 2023;41(16_suppl):8003–8003.
Bachier CR, Cavo M, Corradini P, Delforge M, Janowski W, Lesokhin AM, Mina R, Paris L, Rosiñol L, Quach H, Goodman GR, Nakamura R, Samineni D, Shah V, Fritsch EW, Berdeja JG. CAMMA 2: a phase I/II trial evaluating the efficacy and safety of cevostamab in patients with relapsed/refractory multiple myeloma (RRMM) who have triple-class refractory disease and have received a prior anti-B-cell maturation antigen (BCMA) agent. J Clin Oncol. 2023;41(16_suppl):TPS8064–TPS8064.
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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Zhao, J., Ren, Q., Liu, X. et al. Bispecific antibodies targeting BCMA, GPRC5D, and FcRH5 for multiple myeloma therapy: latest updates from ASCO 2023 Annual Meeting. J Hematol Oncol 16, 92 (2023). https://doi.org/10.1186/s13045-023-01489-3
- Multiple myeloma
- Bispecific antibody