The MAJESTEC-1 study was presented at ASCO, and appeared concomitantly in the New England Journal of Medicine. In this phase 1/2 study heavily pretreated MM patients (78% triple-class refractory) received escalating doses of teclistamab, a BCMAxCD3 T-cell redirecting antibody. The recommended phase 2 dose (RP2D) has been determined to be a subcutaneous weekly administration of teclistamab at a dose of 1.5 mg/kg with two step-up doses to mitigate cytokine release syndrome.
In the ASCO update on this study, 165 patients received teclistamab at the RP2D. The overall response rate was 63% including 39% with CR or better. The median duration of response was 18.4 months. Median PFS was 11.3 months. Common adverse events included cytokine release syndrome and cytopenias. Infections were also common in these heavily pretreated patients, which is likely explained by the treatment-induced hypogammaglobulinemia.
This novel off-the-shelf available T-cell immunotherapy is an important advent for triple-class refractory MM patients, and contributes to a better survival in this patient subset. Other BCMA-targeting bispecifics also show promising activity with a comparable safety profile in a similar patient population. Studies in earlier settings are ongoing.