Teclistamab continued to elicit deep and durable responses in patients with relapsed/refractory multiple myeloma, irrespective of being triple-class refractory, daratumumab-refractory, or refractory to last line of therapy.
Teclistamab-cqyv (Tecvayli) continued to elicit deep and durable responses in patients with relapsed/refractory multiple myeloma, irrespective of being triple-class refractory, daratumumab (Darzalex)-refractory, or refractory to last line of therapy, according to 2-year follow-up data from the phase 1/2 MajesTEC-1 study (NCT04557098) presented at the 2023 EHA Congress.
At an extended follow-up of 22 months, 43% of patients achieved at least a complete response to therapy. For all patients in the study, the median duration of response was 24 months (95% CI, 16.2–not estimable [NE]). When assessing patients who achieved a complete response to therapy or greater, the median duration of response was not reached (95% CI, 24.0-NE).
With teclistamab, the median progression-free survival was 12.5 months (95% CI, 8.8-17.2), and the median overall response was 21.9 months (95% CI, 16.0-NE).
Any-grade or grade 3/4 hematologic adverse events included anemia (54% and 38%, respectively), neutropenia (72% and 65%), lymphopenia (35% and 33%), and thrombocytopenia (42% and 22%).
Infections were observed in 78% of patients in the study, 52% of which were considered grade 3/4. Several of the key infections that occurred included COVID-19 (27%), respiratory (56%), gastrointestinal (8%), other viral (10%), pneumocystis jiroveci pneumonia (4%), fungal (5%), and hepatitis B (0.6%).
In addition, 72% of patients experienced cytokine release syndrome, of which 0.6% was considered grade 3 and no patients had grade 4/5. Five patients (3%) reported immune effector cell-associated neurotoxicity syndrome (ICANS)-related events, all of which were considered grade 1/2. All events related to ICANS in this study were resolved.
Investigators reduced the dose of teclistamab for 1 patient in phase 1 due to neutropenia. Six deaths were related to treatment, of which 3 were associated with COVID-19.
There are currently 49 patients who remain on the study, and approximately 90% of them are on the every-other-week dose schedule for teclistamab.
Researchers analyzed data from 165 patients with multiple myeloma who received 3 or more prior lines of therapy including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody. Of note, previous treatment with a B-cell maturation antigen (BCMA)-targeted therapy was not allowed in this group of patients.
Patients received teclistamab at 1.5 mg/kg once a week, which is the recommended dose from the phase 2 trial. The option to switch to receiving a dose every other week was offered to patients who achieved at least a partial response to treatment after 4 or more cycles of therapy in phase 1 or at least a complete response for 6 or more months in phase 2.
The primary endpoint of this study was the overall response rate, which was assessed with the International Myeloma Working Group (IMWG) 2016 criteria. The Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 were used to grade adverse effects, whereas the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines were used to ICANS and cytokine release syndrome.
Of the 165 patients in the study who received the recommended phase 2 dose of teclistamab, the median age was 64 years, 58% were male, 26% had high-risk cytogenetics and 12% had International Staging System stage III disease.
Patients were treated with 5 prior lines of therapy (range, 2-14). In particular, 92% of patients were exposed to daratumumab (Darzalex). Ninety percent of patient’s disease was refractory to the last line of therapy, 78% were considered triple-class refractory, 81% were refractory to daratumumab, and 90% were refractory to the last line of therapy.
Sidana S, Moreau P, Garfall A, et al. Long-term follow-up from MAJESTEC-1 of teclistamab, a B-cell maturation antigen (BCMA) X CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM). Presented at the 2023 European Hematology Association Congress; Frankfurt Germany, June 8-11, 2023. Poster 879.