Effect of Talquetamab on Responses in Patients with Relapsed and Refractory Multiple Myeloma with Prior Exposure to T-Cell Redirecting Therapies

Background:

Talquetamab (Talq) is a GPRC5D and CD3 bispecific antibody approved for use in relapsed/refractory multiple myeloma (RRMM) in patients previously treated with at least four lines of therapy, including a proteasome inhibitor (PI), immunomodulatory drug (IMiD), and CD38 monoclonal antibody. Data from the MonumenTAL-1 study showed an overall response rate (ORR) of 63% at 11.8 months median follow-up in patients previously receiving T-cell redirecting therapies (TCRT). Here, we present data further supporting the safety and efficacy of Talq in RRMM patients previously treated with TCRTs, and the possible role of T cell-specific lymphopenia and T cell function in patients with exposure to bispecific antibody (BsAb) therapy, which has been postulated in the literature.

Methods:

We performed a retrospective chart review with IRB approval to identify patients with RRMM, including those previously receiving TCRT, now receiving Talq. T cell data was obtained by flow cytometry of peripheral blood samples taken within 3 months prior to Talq therapy. Patients receiving CRS and ICANS were graded per ASTCT consensus criteria, while responses were graded based on the IMWG response criteria.

Results:

Fifty-five patients who receive Talq were evaluable for response, safety, and survival analyses. Nineteen patients had no prior exposure to BCMA CAR-T therapy (group A); 18 had exposure to BCMA CAR-T (group C); 6 had exposure to BCMA BsAb (group C); and 12 had exposure to both BCMA CAR-T and BCMA BsAb (group D). The median age of each group was 67, 63.5, 63.5, and 70 years old, respectively. Males accounted for 42% (n=8), 56% (n=10), 33% (n=2), and 33% (n=3) of groups A, B, C, and D, respectively. ORR was 68% (n=13), 78% (n=14), 50% (n=3), and 50% (n=6) in groups A, B, C, and D, respectively. CR was seen in 11% (n=2), 61% (n=11), 17% (n=1), and 33% (n=4) of patients in each group, respectively. Time to PFS was 0.67 months, 3.9 months,0.77 months, and 1.63 months in groups A,B, C, and D, respectively. Time to OS was not yet reached. CRS occurred in 68% (n=13), 72% (n=13), 33% (n=2), and 33% (n=4) of patients in groups A, B, C, and D, respectively. ICANS occurred in 16% (n=3), 22% (n=4), 0% (n=0), and 17% (n=2), respectively. Dysgeusia occurred in 53% (n=10), 72% (n=13), 100% (n=6), and 100% (n=12) of patients, respectively. Skin changes occurred in 53% (n=10), 72% (n=13), 50% (n=3), and 50% (n=6) of patients, respectively. Nail changes occurred in 37% (n=7), 56% (n=10), 0% (n=0), and 33% (n=4) of patients, respectively. Interestingly, baseline peripheral blood T cell counts varied significantly between patients with prior exposure to BCMA BsAb therapy and all other groups. The median CD3 count in group C was 387 cells/ml, compared to 709 cells/ml in group A and 712 cells/ml in patients in group B. Similarly, the median CD4 count in group A was 155 cells/ml, compared to 318 cells/ml and 267 cells/ml in groups B and C, respectively. In addition, T regulatory cells represented a median 2.58% of peripheral blood CD4 cells in group C, compared to 4.99% and 5.17% of peripheral blood CD4 cells in groups A and B, respectively.

Conclusions:

This single-center study in patients with heavily pretreated myeloma and prior TCRTs demonstrated favorable ORR and CR rates, comparable to patients in the MonumenTAL-1 trial with and without exposure to prior TCRT. In addition, patients with prior exposure to BCMA BsAb therapy had lower rates of CRS and ICANS but higher rates of dysgeusia. Finally, patients with prior exposure to BCMA BsAb therapy had fewer CD3 T cells, CD4 T cells, and lower percentages of T regulatory cells than patients without exposure to prior BCMA therapy and patients with exposure to prior BCMA CAR-T. This may reflect a possible role of T cell number and function in patients with prior TCRT, particularly in patients with recurrent exposure to therapy (BsAb) versus patients with a single exposure to therapy (CAR-T), which could affect the efficacy of Talq and other BsAb therapies. Updated results will be presented at the meeting..

Castaneda:Legend Biotech: Consultancy; Janssen: Consultancy; BMS: Consultancy. Hansen:BMS: Consultancy, Research Funding; Janssen: Consultancy; Pfizer: Consultancy; Karyopharm: Consultancy, Research Funding. Blue:Sanofi: Speakers Bureau; Pfizer Pharmaceuticals, Oncopeptides, Takeda, Abbvie, Janssen, and Kite Pharmaceuticals: Consultancy. Tobon:Bristol Myers Squibb: Consultancy, Honoraria, Other: Completed non-CE panel discussion; Abbvie: Consultancy, Honoraria, Other: Consultant/Advisory Board; Eli Lilly: Consultancy, Honoraria, Other: Consultant/Advisory Board. Liu:BioLineRx: Consultancy, Honoraria. Freeman:Roche/Genentech: Research Funding; Janssen: Consultancy, Research Funding; ONK therapeutics: Consultancy; Amgen: Consultancy; Incyte: Consultancy; Sanofi: Consultancy; Abbvie: Consultancy; Celgene: Consultancy; Seattle Genetics: Consultancy; BMS: Consultancy, Honoraria, Research Funding. Nishihori:ImmunoGen: Consultancy; Karyopharm: Other: drug only supply to the institution; Medexus: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding. Shain:Takeda: Consultancy; Glaxo Smith Kline: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Research Funding; BMS: Consultancy, Research Funding; Amgen: Research Funding; Abbvie: Research Funding; Karyopharm, Janssen, Adaptive Biotechnologies, GlaxoSmithKline, BMS, Sanofi, and Regeneron: Honoraria; Sanofi: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotech: Consultancy. Baz:AbbVie: Research Funding; Karyopharm Therapeutics: Research Funding; Cellectar: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron: Research Funding; Celgene: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees. Alsina:BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. Grajales-Cruz:Cellectar, Janssen, Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen, Sanovi: Speakers Bureau. Locke:Cowen: Consultancy; EcoR1: Consultancy; Gerson Lehrman Group (GLG): Consultancy; Iovance: Consultancy; Janssen: Consultancy; Allogene: Consultancy, Research Funding; A2: Consultancy; BioPharma Communications CARE Education: Honoraria; Aptitude Health: Honoraria; American Society of Hematology: Honoraria, Other: travel, accomodation, expenses; Society for Immunotherapy of Cancer: Honoraria; Imedex: Honoraria; Clinical Care Options Oncology: Honoraria; Communications CARE Education: Honoraria; Caribou: Consultancy; Calibr: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Bluebird Bio: Consultancy; Amgen: Consultancy; Legend Biotech: Consultancy; Novartis: Consultancy, Research Funding; Sana: Consultancy; Kite, a Gilead Company: Consultancy, Other: institutional, travel, accomodation, expenses, Research Funding; Allogene: Other: Institutional, Research Funding; CERo Therapeutics: Research Funding; Moffitt Cancer Center: Patents & Royalties; Pfizer: Consultancy; Umoja: Consultancy; 2SeventyBio: Other: Institutional, Research Funding; National Cancer Institute: Other: Institutional, Research Funding; Leukemia and Lymphoma Society Scholar in Clinical Research: Other: Institutional, Research Funding.