Safety results from the phase 3 MajesTEC-7 study in patients (pts) with transplant ineligible/not intended newly diagnosed multiple myeloma (NDMM).
Authors: Cyrille Touzeau, Meral Beksac, Evangelos Terpos, Saad Zafar Usmani, Amrita Y. Krishnan, Inger S. Nijhof, Wojciech Janowski, Cyrille Hulin, Sebastian Grosicki, Michel Delforge, Dana McAleer, Sarah Nagle, Yunsi Olyslager, Jonathan Miller, Zoe Craig, Josephine Khan, Tobias Kampfenkel, Salomon Manier, Niels W.C.J. van de Donk
Journal: Journal of Clinical Oncology (2024)

7506 Background: Despite recent advances in the treatment (tx) of transplant ineligible/not intended NDMM, most pts still relapse and require alternative txs, highlighting a need for new frontline tx options with new mechanisms of action to improve pt outcomes. Teclistamab (tec) demonstrated rapid, deep, and durable responses in the MajesTEC-1 trial (NCT03145181/NCT04557098). Preliminary data from the MajesTEC-2 trial (NCT04722146) demonstrated that tec, daratumumab (dara), and lenalidomide (len) combination (tec + DR) is tolerable, with promising efficacy in pts with relapsed/refractory MM and NDMM. The phase 3 MajesTEC-7 (NCT05552222) study will compare tec + DR vs DR + dexamethasone (dex) in pts with NDMM who are ineligible/not intended for ASCT as initial tx. We report the results of the first safety run-in (SRI) from MajesTEC-7. Methods: Eligible patients were aged ≥18 yrs with NDMM and ineligible/not intended for ASCT as initial tx, with measurable disease and an ECOG performance status (PS) score 0–2. Pts in the SRI received tec (step-up dose [cycle 1], QW [cycle 2], Q2W [cycle 3–6], and Q4W [cycle 7+]) + DR (as SOC) until progression, unacceptable toxicity, or death. Response assessments were based on IMWG criteria. Adverse events (AEs) were graded per CTCAE v5.0; cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT criteria. Prophylactic immunoglobulin replacement was highly recommended. Results: As of Nov 27, 2023, 26 pts had received tec + DR (median, 11 cycles; range, 2–14) and 24 pts (92.3%) remained on tx. Median follow-up was 10.2 mo (range, 2–12). At baseline, median age was 72.5 yrs, 11.5% had an ECOG PS score of 2, and 15.4% had ≥1 soft-tissue plasmacytoma. 4 pts (15.4%) deferred transplant. Treatment-emergent AEs (TEAEs) occurred in 100% of pts (grade [gr] 3/4, 22 pts [84.6%]). Infections occurred in 25 pts (96.2%; gr 3/4, 8 pts [30.8%]). CRS occurred in 16 pts (61.5%; all gr 1). ICANS occurred in 1 pt (gr 1). Gr 3/4 TEAEs occurring in ≥3 pts were neutropenia (13 [50%]), febrile neutropenia (5 [19.2%]), thrombocytopenia (4 [15.4%]), COVID-19 (3 [11.5%]), maculo-papular rash (3 [11.5%]), and hypertension (3 [11.5%]). 1 pt discontinued tec + DR due to withdrawal of consent. 2 discontinued len due to TEAEs (gr 3 maculo-papular rash and gr 4 neutropenia). There was 1 death due to a TEAE in cycle 3 (pneumonia influenza). Overall response rate was 92.3% (complete response or better, 73.1%; very good partial response or better, 92.3%). Conclusions: These results from the first SRI of MajesTEC-7 demonstrate a manageable safety profile with early efficacy of tec + DR in NDMM. Two additional SRIs are ongoing investigating tec (less frequent dosing) + DR and talquetamab + DR. Clinical trial information: NCT05552222 .