(OA-13) Post-Induction Outcomes and Updated Minimal Residual Disease Analysis from GMMG-HD10/DSMM-XX (MajesTEC-5): A Study of Teclistamab-Based Induction Regimens in Newly Diagnosed Multiple Myeloma (NDMM)

The multi-cohort, phase 2 MajesTEC-5 trial (NCT05695508) is the first to evaluate teclistamab (Tec), a first-in-class B-cell maturation antigen×CD3 bispecific antibody, combined with standard of care daratumumab (DARA)-based regimens, in patients (pts) with transplant-eligible (TE) NDMM. In an initial analysis of outcomes from 3 induction cohorts, steroid-sparing regimens of Tec with DARA/lenalidomide (DR), ± bortezomib (DVR), led to unprecedented clinical efficacy with manageable safety profiles. Here, we present updated results for these 3 induction therapy cohorts treated with Tec-DR or Tec-DVR, including minimal residual disease (MRD) at 10^–5 and 10^–6 thresholds.

Methods:

Eligible pts aged 18-70 years with TE NDMM received Tec-DR (Arms A/A1) or Tec-DVR (Arm B) as induction therapy. Pts received 6, 28-day cycles (C) of Tec, preceded by 2 step-up doses in C1. In C2-6, Tec 1.5 mg/kg was given QW in Arm A and at 3.0 mg/kg Q4W in Arms A1/B. DARA (1800 mg) was given QW in C1-2 and Q2W in C3-6; lenalidomide (25 mg) was given on Days 1-21 from C2-6. Pts in Arm B also received bortezomib (1.3 mg/m²) QW in C1-6. Dexamethasone (20 mg) was given in C1-4 (Arm A) or C1-2 (Arms A1/B) only. The primary endpoint was the rate of adverse events (AEs) and serious AEs. Among secondary endpoints, post-induction MRD negativity was assessed at 10^–5 and 10^–6 thresholds by next-generation flow cytometry (NGF) and next-generation sequencing (NGS), respectively.

Results:

Overall, 50 pts were enrolled and 49 received ≥1 dose of study treatment (Arm A, n=10; A1, n=20; B, n=19); median (range) age was 58 (30-68) years. Two (4.1%) pts discontinued all study treatments due to refusal of further treatment. One, 8, and 2 pts discontinued Tec, lenalidomide and bortezomib, respectively, primarily due to AEs. Median (range) duration of induction treatment was 7.0 (2.5-13.2) months.

Grade 3/4 treatment-emergent AEs (TEAEs) occurred in 44 (89.8%) pts; hematologic TEAEs were most common. Grade 3/4 infections occurred in 17 (34.7%) pts; serious TEAEs occurred in 26 (53.1%) pts. No TEAEs led to full study treatment discontinuation or death. No immune effector cell-associated neurotoxicity syndrome events were reported; cytokine release syndrome occurred in 32 (65.3%) pts, all grade 1/2.

During induction, overall response (≥partial response) was achieved by 100% of pts in all arms. Of 46 MRD-evaluable pts with available samples after C3 and C6, 100% achieved MRD negativity (NGF at 10^–5) at both timepoints. Of 46 MRD-evaluable pts with available samples for NGS after C6, all were MRD-negative at 10^–6. Of 47 pts who completed stem cell mobilization, median stem cell yield was 8.1×10⁶/kg; all except 1 pt had successful stem cell mobilization.

Conclusions:

Tec combined with DR and DVR demonstrates unprecedented clinical efficacy, with 100% of MRD-evaluable pts achieving MRD negativity at 10^–5 and 10^–6 thresholds at completion of induction. Stem cell mobilization was feasible and no new safety concerns were observed.