Dr Bhagirathbhai Dholaria Discusses TRiMM-2 Trial Findings

Bhagirathbhai R. Dholaria, MD, assistant professor of medicine in the Department of Hematology-Oncology at Vanderbilt University Medical Center, discussed findings from the phase 2 TRiMM-2 trial of talquetamab plus daratumumab in relapsed/refractory multiple myeloma.

The findings were presented at the 2023 American Society of Clinical Oncology Annual Meeting.

Transcript

Can you discuss therapeutic rational for combining the bispecific antibody, talquetamab, with the anti-CD38 monoclonal antibody, daratumumab, in patients who have been heavily pretreated for multiple myeloma?

Daratumumab is one of the most effective therapies for newly diagnosed or relapsed/refractory multiple myeloma. And one of the important immunomodulatory effects of datatumumab is actually that it also depletes the CD38 expressing regulatory T cell. The hope was that you can potentially improve the efficacy of talquetamab, which relies on the host T cell function, to attack the cancer and control the myeloma. If you combine both of these together, maybe you can potentiate the antimyeloma activity of talquetamab.

Can you describe the patient population in this study—how many lines of treatment had most received, and how many had received chimeric antigen receptor (CAR) T-cell therapy?

So these patients had relapsed/refractory multiple myeloma with 3 or more prior lines of therapy, and who had double refractory myeloma. We did allow prior exposure to CAR T-cell therapy or other bipecific monoclonal antibody therapy in this trial. These were a heavily pretreated group with a median of 5 or more lines of therapies. A majority of these patients—more than 90%—had [B cell] disease, which is refractory to daratumumab. We also had around 11 patients who had prior CAR T-cell therapy and 15 patients who had prior bispecific antibody drug therapy exposure.

Can you characterize the quality of the responses in these patients?

Responses were encouraging. In the 0.4 mg/kg cohort in combination with daratumumab, around 70% of patients had an overall response rate. Among the patient who were in the 0.8 mg/kg biweekly cohort with daratumumab, the overall response rate was more than 80%, which is slightly better than what we achieve in monotherapy talquetamab now. These responses were rapid and also deepened over time, and very few patients actually required those interruptions [or came] off the trial because of the side effects.

How did cytokine release syndrome (CRS) compare to what is seen following other treatments for multiple myeloma?

CRS was one of the most commonly reported side effects, so it happened the majority of the patients, typically during the cycle 1 of the therapy during this step of dosing. However, most CRS events were grade 1 or grade 2, and they were managed quite well. In terms of neurotoxicity, the overall incidence was low, and all events with neurotoxicity were grade 1 or grade 2.