Teclistamab Monotherapy Tops SOC PVd/Kd in Myeloma, With Phase 3 Data Presented at ASCO 2026

Significant improvements in response depth, minimal residual disease (MRD) negativity, and survival outcomes were seen with teclistamab-cqyv (Tecvayli) monotherapy vs investigator's choice of therapy in patients with relapsed or refractory multiple myeloma who had received 1 to 3 prior lines of therapy, according to findings from the phase 3 MajesTEC-9 trial (NCT05572515) shared during the 2026 ASCO Annual Meeting.¹

At a median follow-up of 17.3 months, teclistamab produced a 71% reduction in the risk of disease progression or death vs standard-of-care (SOC) pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd) or carfilzomib (Kyprolis) plus dexamethasone (Kd; HR, 0.29; 95% CI, 0.23-0.38; P < .0001). The median progression-free survival (PFS) was not reached with teclistamab vs 8.2 months with PVd/Kd. The 18-month PFS rates in the respective arms were 69.8% and 26.9%.

A significant improvement in overall survival (OS) was also reported with teclistamab monotherapy vs PVd/Kd (HR, 0.60; 95% CI, 0.43-0.83; P = .0020). The median OS was not reached in either arm, and estimated 18-month OS rates were 79.2% with teclistamab and 68.6% with PVd/Kd. Investigators noted that the OS benefit was observed despite more than two-thirds of patients in the control arm who received subsequent therapy later receiving a bispecific antibody or CAR T-cell therapy.

“The significant PFS and OS advantage seen with teclistamab monotherapy supports moving this bispecific antibody earlier in the treatment paradigm and reinforces its potential role as a new SOC option for patients with relapsed/refractory multiple myeloma after 1 to 3 prior lines of therapy.” -Roberto Mina, MD, of Winship Cancer Institute of Emory University in Atlanta, Georgia, and AOU Città della Salute e della Scienza di Torino, University of Torino in Italy.

How was the MajestTEC-9 trial designed?

The multicenter, randomized, open-label phase 3 study enrolled patients at least 18 years of age diagnosed with multiple myeloma per International Myeloma Working Group criteria who had measurable disease.² One to 3 prior lines of therapy were required, and these therapies needed to include at least 2 consecutive cycles of an anti-CD38 monoclonal antibody and 2 consecutive cycles of lenalidomide (Revlimid) in any prior line of treatment. Disease progression or lack of response to the last line of therapy was also required, as was an ECOG performance status of up to 2. Patients who had received any prior BCMA-targeting agents were not permitted to enroll, and patients needed to be eligible to receive the control regimen of PVd.

Patients were randomly assigned to receive subcutaneous teclistamab or PVd or carfilzomib/Kd. The regimens were compared in part 1 of the study, and an alternative dosing regimen for teclistamab was also examined in part 2. PFS and the incidence of cytokine release syndrome served as the trial’s primary end points. Secondary end points were overall response rate, very good partial response or better rate, CR or better rate, duration of response, time to next treatment, time to second progression, OS, and safety.

What findings have previously been reported with teclistamab in multiple myeloma?

Results from the phase 3 MajesTEC-3 study (NCT05083169) showcased the clinical potential of teclistamab when leveraged in combination with daratumumab (Darzalex) and hyaluronidase-fihj (Darzalex Faspro).^3,4 At almost 3 years of follow-up, the regimen resulted in an 83% reduction in the risk of disease progression or death compared with SOC (HR, 0.17; 95% CI, 0.12-0.23; P < .0001).

"There are a lot of layers to [the MajesTec-3 trial results], but [the data] are unequivocally impactful and will help [us] move positive outcomes forward for patients across the early relapsed/refractory myeloma setting,” Peter Forsberg, MD, of Colorado Blood Cancer Institute, said in an exclusive interview with OncLive®.⁵

Top-line data from MajesTEC-9 were shared in January 2026.³

What additional efficacy data were reported at ASCO?

Teclistamab produced an overall response rate (ORR) of 84.5% compared with 54.2% with PVd/Kd (OR, 4.62; 95% CI, 3.13-6.83; P < .0001). The rates of complete response (CR) or better were 65.9% and 16.8%, respectively (OR, 10.42; 95% CI, 6.89-15.76; P < .0001). The median duration of response (DOR) was not estimable with teclistamab compared with 13.4 months with PVd/Kd, and the estimated 18-month DOR rates were 80.6% and 40.1%, respectively.

Teclistamab also generated deeper responses, producing MRD-negative CR-or-better rates of 38.5% in the intent-to-treat population compared with 6.7% in the control arm (OR, 8.56; 95% CI, 5.14-14.26). Among MRD-evaluable patients, MRD-negative CR-or-better rates were 86.4% and 45.5%, respectively (OR, 6.80; 95% CI, 3.05-15.16).

Patient-reported outcomes also favored teclistamab. The median time to worsening of multiple myeloma symptoms was not reached with teclistamab compared with 19.48 months with PVd/Kd (HR, 0.50; 95% CI, 0.36-0.71; P < .0001). The corresponding 18-month event-free rates were 73.5% and 55.1%, respectively.

What should be known about teclistamab’s safety profile in MajesTEC-9?

The agent’s safety profile in MajesTEC-9 was consistent with prior experience with teclistamab. Any-grade cytokine release syndrome (CRS) occurred in 66.0% of patients receiving teclistamab, although nearly all events were grade 1 or 2, and all resolved without treatment discontinuation. Grade 3 CRS occurred in 0.7% of patients, with no grade 4 or 5 events reported. Immune effector cell-associated neurotoxicity syndrome was infrequent, with grade 3 events occurring in 0.3% of patients.

Grade 3/4 infections occurred in 41.6% of patients treated with teclistamab vs 29.0% of those receiving PVd/Kd. Investigators reported that rates of grade 3 or higher infections declined after the first 6 months of therapy, coinciding with improved disease control, and emphasized the importance of immunoglobulin replacement therapy and antimicrobial prophylaxis during treatment.

How is MajesTEC-9 relevant for multiple myeloma clinical practice?

“The MajesTEC-9 trial is arguably one of the most practice-relevant ASCO 2026 studies because it basically shifts [a bispecific antibody] up from a salvage therapy to an early-relapse immune therapy option as monotherapy, not as a daratumumab/teclistamab combination. In MajesTEC-9, teclistamab monotherapy was compared with PVd or carfilzomib plus dexamethasone after 1 to 3 previous lines of therapy in a population that was previously exposed to an anti-CD38 antibody and lenalidomide,” Diana Cirstea, MD, of Massachusetts General Hospital and Harvard Medical School in Boston, Massachusetts, told OncLive in an exclusive ASCO 2026 preview.⁶ “The important aspect here is that these are patients who have seen anti-CD38 monoclonal antibody therapy, as opposed to the MajesTEC-3 trial [population], where only approximately 5% of patients were [previously] exposed to daratumumab.

“The top-line reporting already indicates very encouraging PFS and OS with [teclistamab] as compared with the standard regimens,” she added. “Now, the question is: How safe is it? What’s the infection risk, and would it be feasible to implement [teclistamab monotherapy] in the community setting, given the step-up dosing logistics? What’s the benefit across early-relapse subgroups and high-risk groups, as opposed to standard ones? Those will be very interesting data.”

References

1. Mina R, Touzeau C, Hungria V, et al. MajesTEC-9: a phase 3 randomized study of teclistamab monotherapy vs investigator’s choice of pomalidomide, bortezomib, and dexamethasone or carfilzomib and dexamethasone (PVd/Kd) in patients (pts) with relapsed refractory multiple myeloma (RRMM). J Clin Oncol. 2026;44(suppl 16):7507. doi:10.1200/JCO.2026.44.16_suppl.7507
2. A study comparing teclistamab monotherapy versus pomalidomide, bortezomib, dexamethasone (PVd) or carfilzomib, dexamethasone (Kd) in participants with relapsed or refractory multiple myeloma (MajesTEC-9). ClinicalTrials.gov. Updated February 13, 2025. Accessed May 21, 2026. https://clinicaltrials.gov/study/NCT05572515
3. Tecvayli monotherapy demonstrates superior progression-free and overall survival versus standard of care as early as first relapse in patients with multiple myeloma predominantly refractory to anti-CD38 therapy and lenalidomide. Johnson and Johnson. News Release. January 14, 2026. Accessed May 21, 2026. https://www.jnj.com/media-center/press-releases/tecvayli-monotherapy-demonstrates-superior-progression-free-and-overall-survival-versus-standard-of-care-as-early-as-first-relapse-in-patients-with-multiple-myeloma-predominantly-refractory-to-anti-cd38-therapy-and-lenalidomide
4. Unprecedented results from the phase 3 MajesTEC-3 study support Tecvayli plus Darzalex Faspro as a potential standard of care as early as second line for patients with relapsed/refractory multiple myeloma. Johnson and Johnson. News Release. December 9, 2025. Accessed May 21, 2026. https://www.jnj.com/media-center/press-releases/unprecedented-results-from-the-phase-3-majestec-3-study-support-tecvayli-plus-darzalex-faspro-as-a-potential-standard-of-care-as-early-as-second-line-for-patients-with-relapsed-refractory-multiple-myeloma
5. Forsberg P. Dr Forsberg on the impact of the MajesTEC-3 trial in relapsed/refractory myeloma. OncLive.com. December 16, 2025. Accessed May 21, 2026. https://www.onclive.com/view/dr-forsberg-on-the-impact-of-the-majestec-3-trial-in-relapsed-refractory-myeloma
6. Ryan C, Kandel R. Frontline combos take the spotlight: previewing the top hematologic oncology presentations at ASCO 2026. OncLive.com. May 21, 2026. Accessed May 21, 2026. https://www.onclive.com/view/frontline-combos-take-the-spotlight-previewing-the-top-hematologic-oncology-presentations-at-asco-2026