The FDA has granted accelerated approval to talquetamab-tgvs, branded as Talvey, for treating relapsed or refractory multiple myeloma in adults who have undergone at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.
The decision followed compelling results from the Phase II MonumenTAL-1 trial (NCT04634552), which showcased noteworthy overall response rates (ORRs) among patients who had received 4 prior lines of therapy and hadn’t undergone T-cell redirection therapy. Subcutaneous talquetamab, administered biweekly at doses of 0.8 mg/kg, achieved an impressive ORR of 73.6%. Moreover, 58% of patients experienced a very good partial response (VGPR) or better, with a complete response (CR) or better rate of 33%.
Related: Bispecific Antibodies In Multiple Myeloma: A Combination Leads To Durable Responses
Patients treated weekly with a dose of 0.4 mg/kg achieved an ORR of 73.0%, including 57% with VGPR or better and 35% with CR or better. The median duration of response (DOR) was not reached for the 0.8 mg/kg cohort, while it stood at 9.5 months for the 0.4 mg/kg group. Encouragingly, around 85% of responders in the 0.8 mg/kg group maintained their response for at least 9 months.
MonumenTAL-1, encompassing Phase I (NCT03399799) and Phase II (NCT04634552) trials, demonstrated the safety and efficacy of talquetamab. Phase II examined subcutaneous talquetamab’s effectiveness at doses of 0.4 mg/kg per week and 0.8 mg/kg every two weeks.
These groundbreaking findings come against the backdrop of a treatment landscape that includes patients exposed to bispecific antibody or CAR-T cell therapy. Even among this subset, the ORR for those receiving 0.4 mg/kg per week was an impressive 72%, with an estimated 59% maintaining their response for at least 9 months.
However, safety remains a concern, as indicated by talquetamab’s box warning for cytokine release syndrome (CRS) and neurologic toxicity. The trial recorded common adverse effects (AEs) such as pyrexia, CRS, dysgeusia, and musculoskeletal pain. Moreover, a notable proportion of patients experienced weight loss and serious infections.
The regulatory approval for Talvey marks a significant milestone in the treatment of relapsed or refractory multiple myeloma. Its positive impact on overall response rates and durability of response, even in patients with prior exposure to advanced therapies, underscores its potential as a transformative therapy in this challenging disease landscape. However, diligent monitoring and management of adverse effects, particularly CRS and neurologic toxicity, will be essential to ensure the safety and well-being of patients undergoing this innovative treatment.
