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Teclistamab Demonstrates Continued Deep, Durable Responses in Long-Term Follow-Up From MajesTEC-1 Trial
Notably, of the 38 participants who remained on treatment, 37 have switched to less frequent dosing and all have maintained responses.
Long-term follow-up data from the MajesTEC-1 trial (NCT04557098) of teclistamab-cqyv (Tecvayli; Johnson & Johnson) show continued deep and durable responses in patients with relapsed/refractory multiple myeloma (MM), including those who switched to less frequent dosing. Importantly, these results mark the longest follow-up of any bispecific antibody in MM.1
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Teclistamab was the first approved B-cell maturation antigen (BCMA) x CD3 bispecific antibody with weight-based dosing for patients with triple-class exposed relapsed/refractory MM.1 Data from the MajesTEC-1 trial presented in 2022 showed that among 165 patients who received teclistamab, the overall response rate was 63%, with 65 patients (39.4%) having a complete response (CR) or better. Furthermore, 44 patients (26.7%) had no minimal residual disease (MRD) and the MRD-negativity rate among patients with a complete response or better was 46%.2
Additionally, the duration of response (DOR) was 18.4 months, and the median duration of progression-free survival (PFS) was 11.3 months. Cytopenias and infections were common and toxic effects consistent with T-cell redirection were primarily grade 1 or 2.2
The new data, presented at the International Myeloma Society 2024 Annual Meeting in Rio de Janeiro, provide long-term follow-up data. Eligible patients received teclistamab at the recommended phase 2 dose of 1.5 mg/kg subcutaneous once weekly following step-up dosing, with the option to switch to every-other-week dosing if a partial response or better was observed after 4 or more cycles of therapy or if CR or better for 6 or more months was achieved. Patients not in CR or better could switch due to adverse events, and patients could subsequently switch to less frequent dosing if they continued to demonstrate a response. The primary end point was overall response rate.1
At a median follow-up of 30.4 months, 165 patients had received teclistamab at the recommended phase 2 dose. The overall response rate was 63% and responses continued to deepen, with 46.1% achieving CR or better. Furthermore, 85.7% of MRD-evaluable participants were MRD negative.1
The median DOR increased to 24 months while median PFS and overall survival (OS) increased to 11.4 and 22.2 months, respectively. Among patients with CR or better, median DOR, median PFS, and median OS were not yet reached. The estimated 30-month DOR, PFS, and OS rates were 60.8%, 61%, and 74.2%, respectively. Notably, of the 38 participants who remained on treatment, 37 have switched to less frequent dosing and all have maintained responses.1
Hematologic adverse events (AEs) of any grade included neutropenia (72% of any grade, 65% grade 3/4), anemia (55%/38%), thrombocytopenia (42%/23%), and lymphopenia (36%/35%). Infections occurred in 79% of patients (55% grade 3/4) and of the grade 5 infections, 18 of 22 were due to COVID-19. Onset of new grade 3 or higher infections generally decreased over time, reflecting the median time of switch to every-other-week dosing and potentially other factors such as increased use of intravenous immunoglobulin (IVIG). AE leading to discontinuation or dose reduction were infrequent, at 8 and 1, respectively.1
“I think where [pharmacists] have been super helpful for our team is with IVIG and the risk of infections after BCMA bispecifics,” Rahul Banerjee, MD, FACP, from Fred Hutchinson Cancer Center, said in an interview with Pharmacy Times. “There’s a recent study that [infections risk] is higher with BCMA bispecifics than with BCMA CAR T after the first month, so our pharmacists have been extraordinary. They’ve really managed who gets IVIG, what thresholds do we use for IVIG?”
Banerjee added that pharmacists’ knowledge about management of infections and other AEs makes them crucial members of the treatment team.
“I think pharmacists know how to treat infections better than physicians do in a lot of ways, in terms of the actual dosing and details and so forth,” Banerjee said.
Based on these findings, the investigators concluded that teclistamab continues to demonstrate clear deep and durable responses, even in individuals who switched to less frequent dosing. The safety profile also remains consistent with a notable decrease in new onset of severe infections over time.1
