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Promising depth of response and consistent safety profile support the use of talquetamab as a combination agent.
In an abstract presented during an oral presentation at the 21st International Myeloma Society (IMS) Annual Meeting, new results from the phase 1b TRIMM-2 (NCT04108195) study were highlighted. Results showed that the combination of talquetamab (Talvey; Janssen Pharmaceuticals), daratumumab (Darzalex; Janssen Biotech), and pomalidomide (Pomalyst; Bristol Myers Squibb) demonstrated a promising durability and depth of response in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM).1
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Talquetamab is a G protein-coupled receptor class C group 5 member D (GPRC5D)xCD3 bispecific antibody, the first approved of its kind for RRMM. The FDA granted the treatment accelerated approval in August 2023 for adults with RRMM who have had at least 4 previously administered lines of therapy.2
By binding to GPRC5D and CD3, talequetamab induces T-cell-mediated elimination of GPRC5D-expressing MM cells. In the clinical trial prompting its accelerated approval, preclinical models indicated that talquetamab induced the death of MM cells and inhibited the formation and growth of tumors.2
Initial results of the TRIMM-2 trial demonstrated the efficacy of talquetamab and daratumumab (tal+dara) every other week in this patient population. In updated results with a longer follow-up, Dholaria et al found an overall response rate (ORR) of 78%, with deepening responses over the course of treatment. Bahlis et al aimed to investigate the tal+dara combination with the addition of pomalidomide (tal+dara+pom) in patients with RRMM.1,3
Over the course of the trial, 77 patients received tal+dara+pom, with a median follow-up of 17.5 months. Across the median of 6.8 years since diagnosis median lines of therapy was 6. All patients enrolled in the trial had at least 1 adverse event, with the most common being dysgeusia (79.2%), neutropenia (77.9%), cytokine release syndrome (74.0%), dry mouth (64.9%), and fatigue (57.1%), according to the study authors.1
1. The combination of talquetamab, daratumumab, and pomalidomide led to a strong response in patients with relapsed/refractory multiple myeloma.
2. Safety profiles were consistent with those of previous studies.
3. Results demonstrate the use of talquetamab as a combination agent with monoclonal antibodies.
Patients’ ORR was 81.8%, an improvement from the initial results of TRIMM-2, perhaps due to the immunomodulatory effects of dara+pom strengthening talquetamab’s efficacy. Median duration of response was 22.1 months (95% CI, 13.6-27.0), while 53.2% of patients had a complete response or better. The median time to first observed response was 1.0 months (range, 0.6-6.7, and the median progression-free survival was measured to be 15.5 months (95% CI, 11.7-24.4). Critically, responses were found to be deep and durable in anti-CD38 refractory and prior T-cell redirection-exposed patients.1
This year’s IMS meeting has had a major focus on immunotherapies and the promise they hold in transforming MM treatment. An industry symposium with an expert panel discussed the evolution of these therapies, including bispecific and monoclonal antibodies like the therapies in featured in the abstract. Research is poised to continue at a rapid clip in the immunotherapy space for MM treatment.4
