Teclistamab Induction Shows Feasibility in Transplant-Eligible Myeloma

Induction therapy consisting of teclistamab-cqyv (Tecvayli) plus daratumumab (Darzalex) and lenalidomide (Revlimid), with or without bortezomib (Velcade), was feasible and elicited deep responses among patients with transplant-eligible, newly diagnosed multiple myeloma (NDMM), according to a prespecified pooled analysis of the phase 2 GMMG-HD10/DSMM-XX/MajesTEC-5 trial (NCT05695508) published in Nature Medicine.¹

What efficacy did the MajesTEC-5 analysis show?

Among 49 evaluable patients, the overall response rate (ORR) was 100% in arms A (n = 10/10), A1 (n = 20/20), and B (n = 19/19). The cumulative minimal residual disease (MRD)-negative complete response (CR) rate was 91.8% (n = 45/49) by the premaintenance timepoint. All evaluable samples achieved MRD negativity at the 1×10⁻⁵ threshold by next-generation flow cytometry at postinduction cycle 3 (n = 46/46), cycle 6 (n = 46/46), and premaintenance (n = 40/40), as well as at the more stringent premaintenance 1×10⁻⁶ threshold by next-generation sequencing at cycle 6 (n = 46/46). A CR or better was reached by 100%, 90.0%, and 89.5% of patients in arms A, A1, and B, respectively.

At a median follow-up of 12.3 months (range, 3.1-14.5), no disease progression events had occurred. The total median CD34-positive stem cell yield was 8.1×10⁶ per kg (range, 2.6-15.9), surpassing the per-protocol minimal and ideal targets.

What was the safety profile of teclistamab-based induction?

All 49 patients reported a treatment-emergent adverse event (TEAE); grade 3 or 4 events occurred in 91.8% (n = 45/49), and no grade 5 events occurred. Most grade 3 or 4 TEAEs were hematologic, including lymphopenia (59.2%), neutropenia (59.2%), and leukopenia (18.4%). Serious TEAEs occurred in 55.1% (n = 27/49). Any-grade infections were reported in 81.6% (n = 40/49) and grade 3 or 4 infections in 36.7% (n = 18/49), with COVID-19 and pneumonia (6.1% each) being the most common high-grade infections. No grade 5 infections occurred.

Cytokine release syndrome occurred in 67.3% of patients (n = 33/49); all events were grade 1 or 2, resolved, and did not result in treatment discontinuation. No treatment-related immune effector cell–associated neurotoxicity syndrome events were reported.

“Collectively, the positive early clinical efficacy and manageable safety profile observed here in this premaintenance analysis of the ongoing GMMG-HD10/DSMM-XX (MajesTEC-5) study supports the feasibility of the innovative [teclistamab plus daratumumab/lenalidomide] combination, with or without bortezomib, as a promising immune-based, steroid-sparing frontline induction treatment for NDMM,” lead study author Marc S. Raab, MD, PhD, a professor of medicine and clinical director of the Heidelberg Myeloma Center in the Department of Medicine V at the Heidelberg University Hospital, wrote with coauthors in the publication.¹

What was the MajesTEC-5 trial design?

GMMG-HD10/DSMM-XX (MajesTEC-5) is an ongoing, multicenter, open-label, nonrandomized, multicohort phase 2 study in patients 18 to 70 years of age with NDMM who were eligible for high-dose therapy and autologous stem cell transplantation (ASCT). The pooled analysis included 49 patients who received at least 1 dose of study treatment across 3 induction cohorts: teclistamab plus daratumumab/lenalidomide in arms A (n = 10) and A1 (n = 20), and teclistamab plus daratumumab, lenalidomide, and bortezomib in arm B (n = 19). Patients received high-dose melphalan (Alkeran) and ASCT through the premaintenance timepoint. The primary end point was the incidence and severity of AEs and serious adverse events; secondary end points included ORR, MRD negativity, and MRD-negative CR.

The median age was 58.0 years (range, 30.0-68.0), and 20.4% of patients had high cytogenetic risk. Additionally, most patients were male (63.3%), and all were Caucasian (100.0%). Most of the population had an ECOG performance status of 0 (53.1%) and International Staging System disease stage I (57.1%).

How does teclistamab work, and what is its role in multiple myeloma?

Teclistamab is a first-in-class bispecific antibody targeting CD3 on T cells and BCMA on myeloma cells. Combining it with daratumumab is intended to create a more sensitive immune microenvironment that augments the cytotoxic antimyeloma activity. Previously, the FDA approved teclistamab plus daratumumab for relapsed or refractory multiple myeloma after at least 1 prior line of therapy in March 2026 under the National Priority Voucher Program, which was supported by findings from the phase 3 MajesTEC-3 trial (NCT05083169).²

Overall, the investigators concluded that the MajesTEC-5 data support the feasibility of teclistamab-based induction in transplant-eligible NDMM, with notable early MRD negativity rates. However, they noted that longer follow-up is needed to clarify the contribution of bortezomib.

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. Published online June 25, 2026. doi:10.1038/s41591-026-04471-x
2. FDA grants third approval under the National Priority Voucher Program. News release. FDA. March 5, 2026. Accessed June 26, 2026. https://tinyurl.com/45hhbpau