Ajai Chari, MD from the Mount Sinai School of Medicine discusses the TRiMM-2 study of teclistamab and talquetamab in combination with daratumumab in the treatment of relapsed/refractory multiple myeloma. Results from this study were recently presented in two abstracts at ASH 2021.

Multiple myeloma is a rare blood cancer associated with uncontrolled growth of plasma cells. Abnormal plasma cells – also known as myeloma cells – interfere with the production of healthy blood cells in the bone marrow. Myeloma cells also produce inactive clones of abnormal antibodies that may negatively affect the bones and kidneys. Symptoms of multiple myeloma may include: bone pain (particularly in the chest and spine), frequent infections, weakness or numbness in the legs, fatigue, confusion, excessive thirst, and constipation. While the disease is treatable, relapses are common and some patients are refractory to first line treatment.

As Dr. Chari explains, the TRiMM-2 study (NCT04108195) is an ongoing phase 1b study to determine phase 2 doses for each treatment combination (between daratumumab plus talquetamab, and teclistamab plus daratumumab with or without pomalidomide) and to characterize the safety profiles of the combinations. Both talquetamab and teclistamab have been shown to be effective as monotherapies in other clinical trials. In two ASH 2021 abstracts (Abstract 1647 and Abstract 161), results from the TRiMM-2 study were reported; Dr. Chari presented data from the latter abstract which reports initial findings of talquetamab plus daratumumab in relapsed/refractory multiple myeloma patients. 

As of Jul 23, 2021, 23 patients were administered talquetamab plus daratumumab in separate cohorts: daratumumab 1800 mg + talquetamab 400 µg/kg weekly (n=8), + talquetamab 400 µg/kg biweekly (n=5), and + talquetamab 800 µg/kg biweekly (n=10). Median follow-up across the talquetamab plus daratumumab cohorts was 2.9 months. Patients had received a median of 6 prior lines of therapy; 82.6% were triple-class exposed (82.6% received prior daratumumab and 8.7% received prior isatuximab) and 73.9% were penta-drug exposed. Any grade adverse events (AEs) were reported in 95.7% of patients and grade 3/4 AEs in 78.3%. The most frequently reported AEs were dysgeusia, thrombocytopenia, anemia, cytokine release syndrome, and skin exfoliation. One patient in the daratumumab 1800 mg + talquetamab 400 μg/kg biweekly cohort died due to disease progression. 

The median time to first response across talquetamab plus daratumumab cohorts was 1.0 month, and median duration of response was not reached. The pharmacokinetic profile of talquetamab was similar to that observed in the phase 1 monotherapy study. 

Overall, talquetamab in combination with daratumumab was well tolerated, with a safety profile comparable to the monotherapies, and showed promising efficacy in patients with relapsed/refractory multiple myeloma. These findings support further clinical development of talquetamab plus daratumumab combination therapy.

To learn more about multiple myeloma and other rare cancers, visit checkrare.com/diseases/cancers/