Single Center Institutional Experience and Outcomes Administering Both Anti-BCMA and Anti-GPRC5D Bispecific T-Cell Engagers

Background: Bispecific antibodies (BsAb) have changed the treatment landscape of relapsed and/or refractory myeloma (RRMM) in recent years showing high response rates as monotherapy in heavily pretreated patients. There are now three commercially available BsAb for approved for RRMM after four prior lines of therapy. Two of these agents target B-cell maturation antigen (BCMA), Teclistamab (Tec) and Elranatamab (Elra), and the third targets G-protein coupled receptor class C family 5 member D (GPRC5D), Talquetamab (Talq). Here, we describe our institutional experience administering these TCEs in the clinical setting.

Methods: 141 patients received 157 bispecific antibodies commercially with both BCMA and GPRC5D BsAb from 12/21/22 until 6/28/24 at Winship Cancer Institute of Emory University. Demographic and clinical characteristics and outcomes data were obtained from our institutional review board-approved myeloma database and with manual abstraction. Responses and progression were evaluated per International Myeloma Working Group Uniform Response Criteria. The median follow up for the entire cohort was 7.1 months (teclistamab vs elranatamab vs talquetamab were 10.2 vs 4.2 vs 4.2 months).

Results: Of the 157, 76 (48.4%) were treated with Tec, 24 (15.2%) received Elra, and 57 (36.3%) received Talq. The median age for all patients was 66 (range, 38-89) with no statistically significant difference between the three cohorts. The ORR and ≥VGPR rates are 75.1% and 67.6% for Tec, 52.2% and 43.4% for Elra, and 68% and 46% for Talq. The ORR and ≥VGPR rates for the BCMA BsAb combined was 69.3% and 61.6%. The median PFS for patients treated with Tec, Elra, and Talq respectively was 12.85 mo (95% CI 10.76-14.92), NR and NR, due to shorter follow up. Transition to every 2-week dosing was done in 56.8% patients with Tec, 29.2% in Elra, and 43.6% in Talq. Further dose reduction to every 4 weeks was done in 46.4% Tec patients, 8.3% Elra, and 16.7% Talq. Of patients receiving an BCMA BsAb, 14.9% had prior CAR-T cell therapy, 4.0% had prior BsAb, and 10.9% had prior ADC compared to 40.4%, 45.6%, and 15.8% in patients receiving Talq. Almost all patients received Tocilizumab (94.8% vs 100% vs 100%) per our previously published institutional practice of prophylactic dosing prior during ramp up. All grade CRS for BCMA vs GPRC5D BsAb was 27.7% (tec 33.8% vs elra 8.8%, p=0.030) vs 21.4%, respectively. All grade ICANS for BCMA vs GPRC5D BsAb was 11% (tec 7.9% vs elra 20.8%, p=0.20) vs 10.7%, respectively. The rates of grade 3/4 CRS were (3.8% vs 6.6% vs 5.2%) and grade 3/4 ICANS were (0% vs 8.6% vs 3.5%).

Conclusion: The administration of both anti-BCMA and anti-GPRC5D bispecific antibodies is feasible in the clinical practice setting with similar efficacy as seen in the clinical trial setting despite a more heavily pretreated population. Of note, initial administration was limited to patients with significant tumor burden and decreased performance status with limited treatment options likely explaining some of the decreased ORR and increased toxicity. Further, we demonstrate that decreased frequency is feasible while sustaining responses.

Hofmeister:BMS: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding. Kaufman:Sebia: Consultancy, Honoraria; Genentech: Consultancy; Sanofi: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Ascentage: Consultancy, Honoraria. Dhodapkar:Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Lava Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees. Lonial:TG Therapeutics Inc (no cancer agents currently): Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb, Janssen Biotech Inc, Novartis, Takeda: Research Funding; AbbVie Inc, Amgen Inc, Bristol Myers Squibb, Celgene Corporation, Genentech, a member of the Roche Group, GSK, Janssen Biotech Inc, Novartis, Pfizer Inc, Regeneron Pharmaceuticals Inc, Takeda Pharmaceuticals USA Inc: Membership on an entity's Board of Directors or advisory committees. Nooka:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectar Biosciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sebia: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; ONK Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; K36 Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Aduro Biotech: Research Funding; Arch Oncology: Research Funding; Cellectis: Research Funding; Kite Pharma: Research Funding; Merck: Research Funding. Joseph:J&J Oncology: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Research Funding; GSK: Honoraria, Research Funding; Pfizer Oncology: Research Funding; AstraZeneca: Research Funding.