The multicenter, randomized, open-label phase III study MajesTEC4/EMN30 aims to improve durability of response in patients with newly diagnosed multiple myeloma (NDMM) by pairing teclistamab (Tec), a B-cell maturation antigen x CD3 bispecific antibody, with lenalidomide (Len), the current standard of care for maintenance in this population. During the 66th American Society of Hematology Meeting and Exposition, Elena Zamagni, MD, from the University of Bologna in Italy, presented initial results confirming the safety and efficacy of Tec alone or in combination with Len as fixed-duration maintenance therapy following autologous hematopoietic cell transplant in patients with NDMM.
The trial included 91 adult patients (median age = 55) with NDMM who achieved partial response or better after receiving four to six cycles of a triplet or quadruplet induction regimen.
Cohorts one (n=32) and two (n=32) tested the combination of Tec-Len at two different Tec doses, and cohort three (n=30) tested Tec alone. Cohort one was given Tec at 1.5 mg/kg once weekly for two cycles, 3 mg/kg once every two weeks in cycles 3-6, and 3 mg/kg monthly in cycles 7 and onward. Patients in cohorts two and three received Tec at 1.5 mg/kg on days 8 and 15 followed by 3 mg/kg monthly in cycles 2 and beyond. Cohorts one and two also received Len at a dose of 10 mg daily in cycles 2-4, and, if tolerated, 15 mg onward.
Median follow-up was 21.1 months in cohort one and 9.2 months in cohorts two and three. Primary endpoints were progression free survival and 12-month measurable residual disease (MRD)-negative complete response (CR).
“Unprecedented efficacy was observed,” Dr. Zamagni said, with 100% of patients with MRD assessments maintaining or achieving MRD-negative status during maintenance. Additionally, 100% of patients in cohort one achieved a CR or better, and 90.6% and 93.3% in cohorts two and three achieved a CR or better, respectively.
As of September 9, 2024, 86.2% of patients remained on treatment. In total, 5.3% of patients discontinued due to treatment-emergent adverse events. One patient died from COVID-19 prior to the start of Len.
At six weeks, cohort two showed a lower cumulative incidence of grade 3 or 4 neutropenia than cohort one (81.3% vs. 56.3%). Overall, grades 1 and 2 cytokine release syndrome (CRS) rates were between 40% and 50% but reduced after step-up doses 1 and 2, indicating that “it’s feasible to treat in an outpatient setting in the randomized portion of the trial,” Dr. Zamagni said. No discontinuations were due to CRS. No immune effector cell-associated neurotoxicity syndrome was observed.
Hypogammaglobulinemia was observed in 96.9%, 78.1%, and 93.3% of patients in cohorts one, two, and three, respectively. All patients received intravenous immunoglobulin, and infection prophylaxis was strongly recommended. “Even with less intense dose scheduling of Tec, we were not able to eliminate grade 3 or 4 infections. Further studies will reveal if MRD can be sustained,” Dr. Zamagni said.
Safety results informed the global randomized portion of the study, which began in July 2024 in more than 130 countries. Researchers will follow a monthly Tec dosing regimen and maintain a primary endpoint of 12-month MRD-negative CR, which was proven to be highly feasible. “It will be a great opportunity to establish a new standard of care without Len,” Dr. Zamagni said.
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Zamagni E, Silzle E, van de Donk N, et al. Phase 3 study of teclistamab (Tec) in combination with lenalidomide (Len) and Tec alone versus Len alone in newly diagnosed multiple myeloma (NDMM) as maintenance therapy following autologous stem cell transplantation (ASCT): safety run-in (SRI) results from the Majestec-4/EMN30 trial program. Abstract 494. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 8, 2024; San Diego, California.
