Dr Raab on Patient Enrollment and the Design of the MajesTEC-5 Trial in NDMM

"This was a multicohort study where we tested different combinations and schedules... We also had a cohort where we added weekly bortezomib to resemble the Dara-VRd regimen from PERSEUS."

Marc S. Raab, MD, a professor of medicine and clinical director of the Heidelberg Myeloma Center in the Department of Medicine V at Heidelberg University Hospital, CCU Molecular Hematology/Oncology, German Cancer Research Center, provided an overview of the design and specific patient enrollment criteria for the phase 2 MajesTEC-5 trial (NCT05695508). This trial was designed to evaluate teclistamab-cqyv (Tecvayli) in combination with daratumumab (Darzalex), lenalidomide (Revlimid), and dexamethasone with or without bortezomib (Velcade) for the treatment of patients with newly diagnosed multiple myeloma.

The patient population enrolled in the study was characteristic of a transplant-eligible group, with a median age of 58.0 years, indicating a relatively young cohort. The study enrolled patients with a substantial disease burden, as 44.9% of the patients were defined as having a high tumor load, indicated by a bone marrow infiltration rate of at least 60%. Furthermore, high-risk markers were identified in 20.4% of the enrolled patients.

MajesTEC-5 was structured as a multicohort study designed to test various combinations and dosing schedules. Several specific arms were created to investigate different approaches. In arm A, patients received teclistamab administered weekly in combination with lenalidomide and daratumumab, with dexamethasone limited only to the first 2 cycles. In arm A1, patients received the same combination regimen as Arm A, but the teclistamab dose was administered monthly instead of weekly. In arm B, patients received the monthly teclistamab schedule, to which weekly bortezomib was added. This specific regimen structure was intended to resemble the established Dara-VRd regimen seen in studies like the phase 3 PERSEUS trial (NCT03710603).

By utilizing this multicohort design, the trial sought to determine the optimal integration and scheduling of the bispecific antibody teclistamab within standard induction regimens for newly diagnosed multiple myeloma, Raab concluded