Dr Dholaria on Updated Efficacy Data From the TRIMM-2 Trial of Talquetamab and Daratumumab in R/R Multiple Myeloma

Bhagirathbhai R. Dholaria, MBBS, assistant professor of medicine, Department of Medicine, Division of Hematology and Oncology, Vanderbilt University Medical Center, discusses additional 10-month follow-up data from the phase 1 TRIMM-2 trial (NCT04108195) of subcutaneous talquetamab and daratumumab (Darzalex) in relapsed/refractory multiple myeloma.

In this multicohort study, adding the monoclonal antibody daratumumab to the bispecific T-cell engager talquetamab was hypothesized to enhance clinical responses for patients with multiple myeloma. Initial data from the phase 1b portion of the study showed that the combination had preliminary efficacy and bolstered immune responses in this patient population.

Updated results from the trial demonstrated that patients who received talquetamab at a weekly dose of 0.4 mg/kg had an overall response rate (ORR) of 71.4%, Dholaria states. The ORR was 84.0% in those who received the 0.8 mg/kg twice-weekly dose. Patients received 1800 mg of subcutaneous daratumumab in both cohorts. Moreover, with an additional 10 months of follow-up, in the 0.8 mg/kg group, patients who were either previously exposed or refractory to anti–CD38-directed therapy experienced ORRs of over 80% with the regimen, Dholaria reports. Moreover, patients who had previously received T-cell redirection therapies had an ORR of 78.9%, he adds.

No new or additive toxicities were seen with the regimen during this period of additional follow-up, Dholaria continues. As expected, most adverse effects (AEs) were hematologic (60%), Dholaria states. The percentage of patients who experienced grade 3 or 4 neutropenia was 28.6% in the 0.4 mg/kg group, and 27.5% in the 0.8 mg/kg group. Infections were predominantly low grade, although the rates of clinically significant grade 3/4 infection risk were 21.4% and 25.5% in the low and high dose talquetamab groups, respectively. However, most severe infections occurred in the first 6 to 8 months of treatment, Dholaria notes.

Dysgeusia and weight loss were generally manageable with dose modifications or other mitigation strategies, Dholaria adds. Dose reduction of talquetamab due to AEsoccurred in 16.9% of patients, and discontinuation occurred in 1.5% of patients. Other AEs seen with the regimen included skin rash, nail toxicity, gastrointestinal toxicities, and facial hair loss, Dholaria concludes.

Dr Dholaria reports serving as a consultant or in an advisory role for Arivan research, Beam Therapeutics, Gamida Cell, Jazz Pharmaceuticals, and Pluristem Therapeutics; he received honoraria from Adaptive Biotechnologies, Curio Science, MJH Healthcare Holdings LLC, and Wiley; he received institutional research funding from Angiocrine Bioscience, Janssen Oncology, MEI Pharma, Orca Bio, Pfizer, Poseida therapeutic, Takeda, WUGEN, Inc; he has stock and other ownership interests with Iovance Biotherapeutics and Syndax.