Teclistamab Monotherapy Improves PFS and OS in Relapsed/Refractory Myeloma

At the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, Roberto Mina, MD, of the Winship Cancer Institute of Emory University in Atlanta, Georgia, presented results from the phase 3 MajesTEC-9 trial (NCT05572515) evaluating teclistamab-cqyv (Tecvayli) monotherapy vs investigator's choice of pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd) or carfilzomib (Kyprolis) and dexamethasone (Kd) in patients with relapsed/refractory multiple myeloma (RRMM) who had received 1 to 3 prior lines of therapy (LOTs).¹

Teclistamab demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS). With a hazard ratio (HR) of 0.29 (95% CI, 0.23–0.38; P<0.0001), teclistamab reduced the risk of disease progression or death by 71% compared with PVd/Kd. The median PFS was not reached with teclistamab vs 8.2 months with PVd/Kd, and the estimated 18-month PFS rate was 69.8% vs 26.9%, respectively. The PFS benefit was consistent across all prespecified subgroups, including patients with anti-CD38–refractory disease (HR, 0.32; 95% CI, 0.24–0.42), lenalidomide (Revlimid)-refractory disease (HR, 0.30; 95% CI, 0.23–0.40), high-risk cytogenetics (HR, 0.27; 95% CI, 0.18–0.41), and ISS stage III disease (HR, 0.46; 95% CI, 0.26–0.83).

Teclistamab also significantly improved overall survival (OS), a key secondary end point. The HR for OS was 0.60 (95% CI, 0.43–0.83; P=0.0020), with estimated 18-month OS rates of 79.2% with teclistamab and 68.6% with PVd/Kd; both median OS values were not reached at the time of analysis. Notably, this OS benefit was achieved despite the fact that more than two-thirds of patients in the PVd/Kd arm who initiated subsequent therapy had received a bispecific antibody or CAR-T cell therapy.

Teclistamab produced significantly deeper and more durable responses. The overall response rate (ORR) was 84.5% with teclistamab vs 54.2% with PVd/Kd (odds ratio [OR], 4.62; 95% CI, 3.13–6.83; P<0.0001), and the complete response (CR) or better rate was 65.9% vs 16.8%, which was nearly 4 times higher with teclistamab (OR, 10.42; 95% CI, 6.89–15.76; P<0.0001). The very good partial response (VGPR) or better rate was 80.1% vs 36.4%.

The median duration of response (DOR) was not estimable (95% CI, 25.2 months–not estimable) vs 13.4 months (95% CI, 10.4–17.3) with PVd/Kd, and the estimated 18-month DOR rate was 80.6% (95% CI, 74.1%-85.5%) vs 40.1% (95% CI, 30.8%-49.1%). Minimal residual disease (MRD) negativity also strongly favored teclistamab: 38.5% of intent-to-treat patients achieved an MRD-negative CR or better with teclistamab vs 6.7% with PVd/Kd (OR, 8.56; 95% CI, 5.14–14.26). Among patients who were MRD evaluable, the MRD-negative CR or better rate was 86.4% vs 45.5% (OR, 6.80; 95% CI, 3.05–15.16).

“This is the second positive phase 3 study along with MajesTEC-3 [NCT05083169] to show a significant PFS and OS benefit in the second-line setting and beyond with teclistamab-based therapy for patients with RRMM,” according to Mina.

MajesTEC-9 enrolled 593 patients with RRMM who had received 1 to 3 prior LOTs, including prior anti-CD38 monoclonal antibody (mAb) therapy and lenalidomide exposure, and no prior B-cell maturation antigen (BCMA)–directed therapy. Patients were randomly assigned 1:1 to receive teclistamab (n=296) or investigator's choice of PVd or Kd (n=297; 69% Kd). The primary end point was progression-free survival (PFS) per independent review committee (IRC) evaluation, with key secondary end points of CR or better rate, OS, and MySIm-Q total symptom score. The data cutoff was October 13, 2025, with a median follow-up of 17.3 months.²

Baseline characteristics were well balanced between arms. The median age was 70 years (range, 34-85) in both arms. Approximately 75% of patients were double refractory to an immunomodulatory drug (IMiD) and an anti-CD38 mAb, and approximately 35% had high-risk cytogenetics, reflecting a heavily pretreated and refractory population. Soft-tissue plasmacytomas were present in 18.2% and 21.9% of patients in the teclistamab and PVd/Kd arms, respectively.

Patient-reported outcomes were consistent with the clinical benefit observed with teclistamab. Time to worsening of myeloma symptoms per the MySIm-Q total symptom score was significantly delayed with teclistamab (HR, 0.50; 95% CI, 0.36–0.71; P<0.0001), with a median value that was not estimable (95% CI, 23.85-not estimable) vs 19.48 months (95% CI, 16.13 months–not estimable) with PVd/Kd, and an estimated 18-month event-free rate of 73.5% (95% CI, 66.5%-79.2%) vs 55.1% (95% CI, 45.2%-64.0%).

The safety profile of teclistamab was consistent with its known profile as a BCMA-directed bispecific antibody. Any-grade treatment-emergent adverse events (TEAEs) occurred in 99.7% of teclistamab-treated patients vs 97.9% with PVd/Kd, with grade 3/4 TEAEs in 84.9% and 76.3%, respectively. Cytokine release syndrome (CRS) occurred in 66.0% of teclistamab-treated patients and was predominantly low grade (grade 1/2, 48.8%/16.5%; grade 3, 0.7%; no grade 4/5 events); all cases resolved without treatment discontinuation.

Immune effector cell-associated neurotoxicity syndrome (ICANS) was infrequent and generally low grade in the teclistamab arm (grade 1/2, 2.4%/1.4%; grade 3, 0.3%). Grade 3/4 neutropenia was the most common hematologic AE, occurring in 54.3% of teclistamab-treated patients vs 22.3% in the PVd/Kd arm. Discontinuations due to TEAEs were lower with teclistamab vs PVd/Kd (10.7% vs 13.1%), and median treatment duration was nearly double with teclistamab (13.1 vs 7.0 months).

Infections were common in the teclistamab arm (any grade, 82.8%; grade 3/4, 41.6%) but declined substantially after 6 months and with the transition to monthly dosing, consistent with disease control. Grade 5 infections occurred in 5.5% of teclistamab-treated patients vs 2.8% with PVd/Kd, with most occurring in patients with low immunoglobulin G (IgG) levels, underscoring the importance of immunoglobulin replacement therapy (IgRT) and antimicrobial prophylaxis. Hypogammaglobulinemia was common in both arms (69.1% with teclistamab vs 50.2% with PVd/Kd).

MajesTEC-9 represents the second positive phase 3 study of teclistamab-based therapy to demonstrate significant PFS and OS benefit in 2L+ RRMM. Together with MajesTEC-3, which supported the FDA approval of the teclistamab and daratumumab combination for RRMM, these results collectively position teclistamab-based therapy as a new second-line or later standard of care across community and academic practice settings.³ The data were simultaneously published in The New England Journal of Medicine.²

References

1. Mina R, Touzeau C, Hungria V, et al. Teclistamab monotherapy vs investigator’s choice of PVd or Kd in relapsed/refractory multiple myeloma: Primary analysis of the phase 3 MajesTEC-9 study. J Clin Oncol. 2026;44(suppl 16):7507. doi:10.1200/JCO.2026.44.16_suppl.7507
2. Touzeau C, Mina R, Hungria V, et al. Teclistamab in multiple myeloma with one to three previous lines of therapy. N Engl J Med. Published online May 39, 2026. doi:10.1056/NEJMoa2603870
3. FDA grants third approval under the National Priority Voucher Program. News release. FDA. March 5, 2026. Accessed May 30, 2026. https://tinyurl.com/45hhbpau