Teclistamab Monotherapy Demonstrates Significant Survival, Response Benefits in RRMM

Outcomes for patients with relapsed/refractory multiple myeloma (RRMM), particularly those refractory to anti-CD38 and lenalidomide-based regimens, remain suboptimal despite major advances in frontline multiple myeloma therapy. Novel immunotherapies, including bispecific antibodies targeting B-cell maturation antigen (BCMA), have reshaped treatment expectations in heavily pretreated disease.

Results from the phase 3 MajesTEC-9 study (NCT05572515) presented at the 2026 American Society of Clinical Oncology Annual Meeting demonstrated that teclistamab (Tecvayli; Janssen Biotech, Inc) monotherapy significantly improves progression-free survival (PFS), overall survival (OS), and depth of response compared with standard-of-care triplet or doublet regimens in patients with 1 to 3 prior lines of therapy.

Expanding the Role of BCMA × CD3 Bispecific Therapy

Teclistamab is a BCMA × CD3 bispecific antibody that redirects T cells toward malignant plasma cells, which produces deep and durable responses in RRMM. Although prior data established its activity in heavily pretreated populations, MajesTEC-9 is the first phase 3 trial to evaluate teclistamab monotherapy earlier in the treatment paradigm, in patients with 1 to 3 prior lines of therapy who were predominantly anti-CD38 and lenalidomide refractory.

Study Design

The MajesTEC-9 trial enrolled 593 patients with RRMM whose prior 1 to 3 lines of therapy included exposure to both anti-CD38 antibodies and lenalidomide (Revlimid; Celgene Corporation). The patients were randomly assigned to receive either teclistamab monotherapy or the researcher’s choice of pomalidomide (Pomalyst; Bristol Myers Squibb), bortezomib (Velcade; Millennium Pharmaceuticals, Janssen Pharmaceutical Companies), and dexamethasone (PVd) or carfilzomib (Kyprolis; Onyx Pharmaceuticals, Inc) and dexamethasone (Kd).

The primary end point was PFS by independent review committee, with key secondary end points including OS, overall response rate, complete response or better (≥ CR), and safety.

Durable Efficacy With Teclistamab

The data revealed that, at a median follow-up of 17.3 months, teclistamab demonstrated a critically significant improvement in PFS vs standard therapy. The median PFS was not reached in the teclistamab arm vs 8.2 months with PVd/Kd (HR, 0.29; 95% CI, 0.23-0.38; P < .0001), corresponding to 18-month PFS rates of 69.8% and 26.9%, respectively.

The overall survival rate was also significantly improved with teclistamab (HR, 0.60; 95% CI, 0.43-0.83; P = .0020), further reinforcing its potential impact on long-term outcomes in earlier-line RRMM. The depth of response strongly favored teclistamab, with CR or greater achieved in 65.9% of patients compared with 16.8% in the PVd/Kd arm (R, 10.42; 95% CI, 6.89-15.76; P < .0001). The data displayed responses that were consistent across high-risk subgroups, including patients refractory to both anti-CD38 therapy and lenalidomide.

Safety Profile Consistent With Known Immune-Related Toxicities

At the time of data cutoff, a larger proportion of patients remained on teclistamab than on standard therapy (65.3% vs 24.0%, respectively), reflecting a longer treatment duration in the investigational arm. The overall adverse effects (AEs) were common in both groups (99.7% vs 97.9%, respectively), with higher rates of grade 3 and 4 AEs (84.9% vs 76.3%) and grade 5 (6.5% vs 3.5%) observed in the teclistamab arm, potentially influenced by longer exposure duration.

Grade 3 and higher infections were more frequent with teclistamab (41.6% vs 29.0% in the investigational arm); however, rates of higher-grade infections decreased over time with continued treatment. Cytokine release syndrome (CRS) occurred in approximately 66.0% of patients (primarily grade 1 and 2), and immune effector cell–associated neurotoxicity syndrome was observed in 4.1% of patients. Established management protocols were effective in controlling these toxicities, with relatively low discontinuation due to adverse events.

Shifting Teclistamab Earlier in the Treatment Paradigm

The data from MajesTEC-9 indicate that earlier use of teclistamab may provide meaningfully improved outcomes compared with current standard regimens in patients with RRMM, including those with extensive prior exposure to key drug classes. The magnitude of benefit in PFS, OS, and response depth supports the potential repositioning of BCMA × CD3 bispecific therapy as a backbone option earlier in the disease course.

Although safety considerations, particularly infections and CRS, remain important, the overall benefit-risk profile observed in this study supports continued integration of bispecific antibodies into earlier lines of therapy for multiple myeloma.

REFERENCE

Mina R, Touzeau C, Hungria V, et al. MajesTEC-9: a phase 3 randomized study of teclistamab monotherapy vs investigator’s choice of PVd/Kd in patients with relapsed refractory multiple myeloma. Presented at: 2026 ASCO Annual Meeting; May 29-June 2, 2026; Chicago, IL. Abstract 7507.