Dr Dholaria on Ongoing Investigations 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 next steps for investigating subcutaneous talquetamab and daratumumab (Darzalex) in relapsed/refractory multiple myeloma based on data from the phase 1 TRIMM-2 trial (NCT04108195).

The multicohort study evaluated whether the addition of daratumumab to the bispecific T-cell engager talquetamab could improve immune responses in patients with multiple myeloma.

Updated findings from the multicohort study were presented at the 2023 ASCO Annual Meeting, showing that both the 0.4 mg/kg and 0.8 mg/kg weekly doses of subcutaneous talquetamab plus daratumumab produced overall response rates (ORRs) of above 70% and no overlapping toxicities. Moreover, patients in the 0.8 mg/kg group who had been previously exposed or were refractory to anti–CD38-directed therapy experienced ORRs of over 80%, and those who had previously received T-cell redirection therapies had an ORR of 78.9% with an additional 10 months of follow-up.

These findings support the continued investigation of the talquetamab and daratumumab in multiple myeloma. Investigators plan to continue following patients and collecting data within this study, Dholaria says. If the regimen demonstrates efficacy and safety outcomes consistent with the data from TRIMM-2, the regimen's further investigation will gain more support, he adds. 

Of note, in August, 2023, talquetamab was granted accelerated approval by the FDA for adults with relapsed/refractory multiple myeloma who have received at least 4 prior lines of therapy, on August 9, 2023. The regulatory decision was based on data from the phase 1/2MonumenTAL-1 trial (NCT03399799, NCT4634552).

In addition to TRIMM-2, there are several ongoing studies evaluating the regimen in combination with established agents, as well as novel myeloma-directed therapies, Dholaria continues. The phase 3 MonumenTAL-3 study (NCT05455320) is evaluating talquetamab and daratumumab with or without pomalidomide, he introdues. Meanwhile, the phase 1/2 RedirecTT-1 trial (NCT04586426) is combining both talquetamab and the T-cell–redirecting bispecific antibody teclistamab (Tecvayli) in patients with relapsed/refractory multiple myeloma or extramedullary disease, Dholaria notes. In the future, studies of talquetamab may attempt to utilize the agent in combination with other immunotherapies, such as immune checkpoint inhibitors, 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.