Real World Outcomes with Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody: A Single Center Experience for Relapsed/ Refractory Multiple Myeloma (RRMM)

Background: Despite the advent of novel therapies including chimeric antigen receptor T-cell (CAR-T) therapy that have provided unprecedented clinical benefit for patients with RRMM, multiple myeloma remains an incurable malignancy in which patients eventually experience relapse. G protein-coupled receptor, family C, group 5, member D (GPRC5D) is an orphan receptor that is expressed in malignant plasma cells. Talquetamab, a bispecific IgG4 antibody, binds to both GPRC5D and CD3 to induce killing of GPRC5D-expressing myeloma cells by means of T-cell recruitment and activation. In this single center retrospective study, we aim to evaluate the real-world effectiveness and outcomes of patients who received talquetamab since the drug received FDA approval in August 2023.

Methods: Following institutional review board approval, we included all patients with MM who were treated with commercially approved Talquetamab therapy. Demographic characteristics, molecular studies, treatment and response information were recorded and included in the study. Safety outcomes included the incidence and severity of adverse events (AEs). AEs were graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE 5.0). Cytokine release syndrome (CRS) and immune effector associated neurotoxicity syndrome (ICANS) were graded as per the American Society for Transplantation and Cellular Therapy criteria. Efficacy outcomes included overall response rates (ORR), progression free survival (PFS), overall survival (OS) and best response achieved. Survival analysis was performed using the Kaplan-Meir method including PFS and OS. The IMW response criteria were utilized for response assessment.

Results: We identified 27 pts who were treated consecutively at Hackensack University Medical Center with talquetamab between September 2023 and May 2024. Pts had a median age of 72 years (range 45-81). Importantly, four (15%) pts had CNS involvement and six (22%) pts had extramedullary disease. Pts had received a median of 8 (range 3-19) prior lines of therapy. 26(94.3%) pts were triple class refractory, and all except two pts (98.1%) had a prior autologous stem cell transplant (ASCT). Fourteen (52%) pts had high-risk FISH defined as those with t(4;14), t(14;16), 17p(-) or 1q(+), eighteen (67%) pts were R-ISS-2 or 3 at diagnosis. Thirteen (59%) pts had prior T-cell receptor therapy with twelve (44%) pts having prior CAR-T, five (19%) pts had prior Bispecific T- cell engager (TCE) and four (15%) pts had both CAR-T and Bispecific TCE.

Treatment was overall well tolerated, with no therapy related mortality. ORR for the entire cohort was 74% with complete remission (CR) achieved in 6 (22%)pts, very good partial remission (VGPR) in 2 (7%)pts and partial remission (PR) in 12 (44%)pts. The median PFS was 5.6 months, with 10 (37%) patients having relapsed and 17 (63%) pts continuing to have response on talquetamab. The mean OS was 7.6 months with 4 (15%) patients deceased. There was no difference in OS and PFS based on whether pts had prior exposure to TCR therapy. Interestingly, of the 12 pts that had prior CAR-T, ORR was 74% although only one pt achieved CR, 8 had PR and 3 had stable disease as the best response. Of 10 pts that relapsed, five had prior CAR-T and one had prior bispecific T- cell engager.

21(78%) pts experienced hematologic toxicity with 3(11%) pts having grade 3 or higher, 12(44%) pts experienced skin toxicity, 11 (41%) pts experienced oral toxicity with one patient experiencing grade 3 skin and oral toxicity leading to early termination of the treatment. Three (11%) pts experienced grade 3 or higher infectious complication requiring hospitalization. 13 pts (48%) patients experienced CRS, with no patient having grade 3 or higher CRS and only one patient experienced grade 2 ICANS.

Conclusion: To our knowledge, this is the first report of commercial talquetmab in RRMM patients that are heavily pretreated and have aggressive disease biology. In summary, we found that talquetamab exhibited a comparable efficacy and safety profile in the real-world setting as in the pivotal trial. Talquetamab is a valuable treatment option for RRMM. Further studies are warranted to evaluate a potential role of talquetamab in less advanced treatment lines or newly diagnosed MM.

Siegel:Sanofi: Honoraria; BMS: Honoraria; Envision Pharma: Honoraria; COTA: Current holder of stock options in a privately-held company; Envision Pharma: Honoraria; Pfizer: Honoraria; Merck: Honoraria; K36 Therapeutics: Honoraria; Roche: Honoraria; Prothena: Honoraria; Sebia: Honoraria. Vesole:Sanofi: Speakers Bureau; Karyopharm: Speakers Bureau; Takeda: Speakers Bureau; Janssen: Speakers Bureau; BMS: Speakers Bureau; Amgen: Speakers Bureau. Biran:Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; AbbVie: Consultancy; Karyopharm: Research Funding; Pfizer: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Research Funding. Parmar:Sanofi: Membership on an entity's Board of Directors or advisory committees; Cellectar Biosciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Data Safety Monitoring/Advisory Board, Research Funding.