Teclistamab-Based Induction Elicits High MRD Negativity Rates in Transplant-Eligible Newly Diagnosed Myeloma

Teclistamab-cqyv (Tecvayli)–based induction regimens generated a minimal residual disease (MRD)–negative complete response (CR) rate of 91.8% (45/49) by the premaintenance timepoint in patients with transplant-eligible, newly diagnosed multiple myeloma, according to data from the phase 2 MajesTEC-5 trial (NCT05695508) published in Nature Medicine.¹

Findings showed the overall response rate (ORR) was 100% (n = 49) across the three induction cohorts, and all patients with evaluable samples achieved MRD negativity by next-generation flow (NGF) cytometry at a sensitivity of 1 × 10⁻⁵ after induction cycle 3 (n = 46), after cycle 6 (n = 46), and at the premaintenance timepoint (n = 40). MRD negativity by next-generation sequencing (NGS) at a 1 × 10⁻⁶ threshold was reached in all evaluable samples after cycle 6 (n = 46), yielding a cumulative MRD negativity rate of 98.0%. At a median follow-up of 12.3 months (range, 3.1-14.5), no progression events had been observed.

The positive early clinical efficacy and manageable safety profile observed here in this premaintenance analysis…supports the feasibility of the innovative teclistamab [plus daratumumab (Darzalex) and lenalidomide (Revlimid)], with or without bortezomib, as a promising immune-based, steroid-sparing frontline induction treatment for newly diagnosed multiple myeloma,” lead study author Marc S. Raab, MD, of Heidelberg University Hospital, wrote in a publication of the data.

How was the MajesTEC-5 trial designed?

MajesTEC-5 (GMMG-HD10/DSMM-XX) is an ongoing, multicenter, open-label, nonrandomized phase 2 study evaluating teclistamab in combination with daratumumab-based induction regimens in patients with transplant-eligible newly diagnosed multiple myeloma. Eligible patients were 18 to 70 years of age and had an ECOG performance status of 0 to 2. The prespecified pooled analysis reported here spanned the induction and autologous stem cell transplantation (ASCT) phases up to the last visit prior to maintenance, referred to as the premaintenance treatment timepoint.

A total of 49 patients received at least one dose of study treatment across three cohorts: arm A received teclistamab at 1.5 mg/kg weekly plus daratumumab and lenalidomide (n = 10); arm A1 received teclistamab at 3.0 mg/kg monthly plus daratumumab and lenalidomide (n = 20); and arm B received Tec-DR plus bortezomib (n = 19). Patients underwent six cycles of induction followed by high-dose melphalan and ASCT.

Safety served as the trial’s primary end point. MRD-negative CR rate was a key secondary end point.

The median age was 58.0 years (range, 30.0-68.0), 44.9% of patients had at least 60% bone marrow plasma cells, and 20.4% had high cytogenetic risk. A total of 46 patients (93.9%) completed all six cycles of induction, with a median induction duration of 7.0 months. Updated MRD and safety data from the three cohorts were previously presented at the 2025 International Myeloma Society Annual Meeting.²

What were the additional efficacy Findings?

Rates of CR or better by the premaintenance timepoint were 100% in arm A, 90.0% in arm A1, and 89.5% in arm B. The cumulative MRD-negative CR rate was 91.8% across arms. Stem cell mobilization was successful in 47 of 49 patients (95.9%), and the median total CD34-positive stem cell yield was 8.1 × 10⁶ per kg (range, 2.6-15.9), surpassing per-protocol minimal and ideal target numbers. Among the 43 patients (87.8%) who underwent ASCT, the median times to neutrophil and platelet engraftment were 12 days and 14 days, respectively.

What did the safety analysis show?

All 49 patients experienced a treatment-emergent adverse effect (TEAE), and grade 3 or 4 TEAEs occurred in 91.8% of patients; no grade 5 TEAEs were reported. The most common grade 3 or 4 TEAEs were hematologic, including lymphopenia (59.2%), neutropenia (59.2%), and leukopenia (18.4%). Serious AEs occurred in 55.1% of patients, with pyrexia (12.2%) the most common.

Cytokine release syndrome (CRS) occurred in 67.3% of patients, predominantly during the step-up dosing schedule; all events were grade 1 or 2, all resolved, and none led to discontinuation of study treatment. No treatment-related immune effector cell–associated neurotoxicity syndrome (ICANS) events occurred. Any-grade and grade 3 or 4 infections were reported in 81.6% and 36.7% of patients, respectively, with COVID-19 and pneumonia (6.1% each) the most common grade 3 or 4 infections; no grade 5 infections were reported. By the premaintenance timepoint, 45 patients (91.8%) had at least one hypogammaglobulinemia TEAE or post-baseline immunoglobulin G level below 400 mg/dL, and 44 (89.8%) received at least one dose of intravenous immunoglobulin. Peripheral sensory neuropathy was reported in 20.4% of patients, all grade 1 or 2.

References

1. Raab MS, Weinhold N, Kortüm KM, et al. Teclistamab-based induction treatment in transplant-eligible, newly diagnosed multiple myeloma: a phase 2 trial. Nat Med. 2026;32(7):2440-2448. doi:10.1038/s41591-026-04471-x
2. GMMG-HD10 /​ DSMM-XX /​ 64007957MMY2003, MajesTEC-5 (HD10/DSMMXX). ClinicalTrials.gov. Updated December 24, 2025. Accessed August 21, 2026. https://clinicaltrials.gov/study/NCT05695508?cond=NCT05695508&viewType=Card&rank=1