Fixed-duration cevostamab consolidation following BCMA-directed CAR-T cell therapy achieved a remarkable 93% minimal residual disease (MRD)-negative complete response rate at one year in heavily pretreated multiple myeloma patients, according to interim results from the phase 2 STEM trial presented at the 22nd Annual International Myeloma Society Meeting and Exposition.
The study demonstrated significant improvement in response rates throughout the treatment sequence. Pre-cevostamab, the complete response rate was 63%, which increased to 81% when given CD81, and reached 93% at one-year post CAR-T cell therapy. "The vast majority of patients are alive and remain progression-free," reported Adam D. Cohen, MD, director of Myeloma Immunotherapy and associate professor of medicine at the Hospital of the University of Pennsylvania, with a median follow-up of 12 months.
Treatment Protocol and Patient Population
The STEM trial enrolled 27 patients with relapsed/refractory multiple myeloma who had received commercial CAR-T cell therapy 6 to 10 weeks prior to enrollment. Patients were required to have four or more prior lines of treatment, including an immunomodulatory drug, proteasome inhibitor, and CD38 antibody, with stable disease or better after CAR-T cell therapy.
Following standard-of-care treatment with either idecabtagene vicleucel (ide-cel; Abecma) or ciltacabtagene autoleucel (cilta-cel; Carvykti), patients enrolled in the STEM trial at 10 to 12 weeks post-treatment. Cevostamab was administered intravenously at 3.6 mg on cycle 1 day 1 and 132 mg on cycle 1 day 8 and thereafter, every 3 weeks for 8 cycles. Patients required 48-hour hospitalization on both infusion days.
The patient population reflected heavily pretreated disease, with a median age of 64 years, 74% male, and 78% White. The median time from diagnosis to study participation was 4.6 years, with 19% having extramedullary disease. Notably, 93% of patients received cilta-cel and 7% received ide-cel, with a median of 4 prior lines of therapy and 74% being triple-class refractory.
Cytogenetic Risk Factors
High-risk cytogenetic features were prevalent, with 44% of patients having t(4;14), t(14;16), or del17p; 59% had gain or amp 1q; and 22% had del 1p. Overall, 74% had at least one of these high-risk features, and 41% had at least two.
Safety Profile
The treatment demonstrated a manageable safety profile. Hematologic adverse events of any grade included lymphopenia (74%), neutropenia (74%), thrombocytopenia (41%), anemia (26%), and febrile neutropenia (4%). Grade 3/4 hematologic events occurred in 67%, 44%, 22%, 0%, and 4% of patients, respectively.
Non-hematologic adverse events of any grade included infections (52%), cough (59%), rash (44%), upper respiratory infection (37%), and cytokine release syndrome (15%). Grade 3/4 non-hematologic events were limited, with infections occurring in 15% of patients and no grade 3/4 cytokine release syndrome reported.
Four patients experienced unusual immune-related adverse events, including grade 2 enterocolitis, grade 3 ataxia/gait disturbance/peripheral neuropathy, grade 3 transaminitis with grade 1 autoimmune hepatitis, and grade 4 immune thrombocytopenia. Notably, three of these four patients had a preceding infection before developing immune-related adverse events. All unusual immune-related adverse events resolved.
Clinical Outcomes
The primary endpoint was the MRD-negative complete response rate at 12 months post-CAR-T cell therapy. After MRD assessment, patients achieving MRD-negative complete response were observed, while those who did not returned to treatment with cevostamab every 3 weeks for an additional 8 cycles.
"To date, over 90% of evaluable patients [are] sustaining MRD-negative CR at 1-year post-CAR T. Enrollment [in the trial] is complete; treatment and follow-up are ongoing," Cohen concluded. The interim analysis had a cut-off date of June 27, 2025, with enrollment now complete and ongoing treatment and follow-up continuing.
