Combination teclistamab, daratumumab, and lenalidomide can produce deep and durable responses in patients with relapsed or refractory multiple myeloma (MM), according to research presented at the 2022 ASH Annual Meeting.
“The activity of this immune-based triplet regime is promising, with rapid responses that deepen over time,” said study investigator Emma Searle, MD, PhD, of the University of Manchester in the United Kingdom.
Dr Searle and colleagues studied the combination in the phase 1b MajesTEC-2 trial (ClinicalTrials.gov Identifier: NCT04722146). Dr Searle presented initial safety and efficacy data of the combination in 32 MM patients who had received 1-3 prior lines of therapy, including a proteasome inhibitor and immunomodulatory drug.
Following step-up dosing, patients received weekly doses of teclistamab at 0.72 mg/kg (n=13) or 1.5 mg/kg (n=19), with a transition to 3 mg/kg once every 2 weeks starting at cycle 3. Patients also received daratumumab at 1800 mg every week in cycles 1-2, every other week in cycles 3-6, and once a month for cycle 7 and beyond. Lenalidomide was given at 25 mg daily for 21 days each cycle, starting at cycle 2. Dexamethasone was given at 40 mg once weekly in cycles 2-4.
At baseline, the median age was 65 years (range, 38-71) in the 0.72 mg/kg cohort and 60 years (range, 46-75) in the 1.5 mg/kg cohort. Most patients (84.6% and 89.5%, respectively) were men. Some patients had disease that was refractory to lenalidomide (46.2% and 15.8%, respectively) or an anti-CD38 antibody (23.1% and 15.8%). Patients in both arms had received a median of 2 prior lines of therapy (range, 1-3).
The median follow-up was 8.4 months. The overall response rate was 93.5%, with 90.3% of patients achieving a very good partial response or better and 54.8% achieving a complete response (CR) or better. The median time to first response was 1.0 month, and the median time to CR or better was 3.0 months.
Dr Searle said these data suggest the combination “has the potential for [producing] deep and durable responses in patients with relapsed/refractory multiple myeloma.”
The most frequent nonhematologic adverse event (AE) was cytokine release syndrome (CRS; 81.3%). All CRS events were grade 1-2. Most CRS events (97%) occurred during cycle 1. There were no cases of immune effector cell-associated neurotoxicity syndrome.
The most common hematologic AE was neutropenia (any grade, 84.4%; grade 3-4, 78.1%). Infections occurred in 90.6% patients (grade 3-4: 37.5%), including upper respiratory infection (31.3%), COVID-19 (37.5%), and pneumonia (25.0%). There were 2 fatal AEs, 1 from COVID-19 and 1 due to multiorgan failure from sepsis.
Disclosure: This research was supported by Janssen Research & Development, LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Searle E, Quach H, Wong SW, et al. Teclistamab in combination with subcutaneous daratumumab and lenalidomide in patients with multiple myeloma: Results from one cohort of MajesTEC-2, a phase1b, multicohort study. Presented at ASH 2022. December 10-13, 2022. Abstract 160.