Teclistamab as Monotherapy Shows Huge Advantage After First Relapse in Myeloma

Teclistamab (Tecvayli; Johnson & Johnson) appears poised to move into earlier lines of care as a monotherapy, as bispecific antibodies made big news in the treatment of blood cancers and disorders on the opening day of the American Society of Clinical Oncology (ASCO) in Chicago.

Phase 3 results for the MajesTEC-9 trial (NCT05572515), presented May 29, 2026, showed a 71% reduced risk of disease progression or death among patients taking teclistamab, compared with those taking either of 2 commonly used combinations.¹

Results, which appeared in the New England Journal of Medicine,² showed that teclistamab, a fully immune-based and glucocorticoid-sparing regimen, was highly effective as a monotherapy in patients with relapsed or refractory (R/R) multiple myeloma who had previously received 1, 2, or 3 lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide. As stated by the study authors, this patient population had been underrepresented in clinical trials.²

The bispecific antibody is currently approved as a monotherapy for patients with 4 prior lines of treatment, and in combination with subcutaneous daratumumab (Darzalex Faspro; Johnson & Johnson) for those with at least 1 prior line of treatment.³

Today, much of the discussion in treatment of blood cancers and disorders centers on moving treatment into the outpatient setting, and bispecifics are central to this cause: They do not require patient-specific manufacturing and the adverse events (AEs) are more manageable than with chimeric antigen receptor (CAR) T-cell therapy. Clinicians are gaining experience with the use of prophylactic agents to prevent AEs with bispecifics, and data to be presented during ASCO will shed light on this process.

Patients in MajesTEC-9 were randomly assigned 1:1 to receive either teclistamab monotherapy—the teclistamab group—or the investigator’s choice of pomalidomide (Pomalyst; Bristol Myers Squibb), bortezomib (Velcade; Takeda), and dexamethasone (PVd) or carfilzomib (Kyprolis; Amgen) and dexamethasone (Kd)—the combination group.

The primary end point was progression-free survival (PFS), with key secondary end points, according to hierarchical testing, being complete response (CR) or better, overall survival (OS), and time to worsening of symptoms. Other secondary end points included overall response (OR), duration of response, time to response, and safety.

“These findings further reinforce [teclistamab’s] potential to meaningfully improve survival outcomes for patients with multiple myeloma in earlier lines," Roberto Mina, MD, associate professor, Winship Cancer Institute of Emory University and coauthor of MajesTEC-9, said in a statement emailed to The American Journal of Managed Care^®. “These results will continue to transform the role of bispecifics in clinical decision-making as early as first relapse—offering a steroid-sparing, community-based therapy for patients across all practice settings, regardless of prior anti-CD38 exposure.”

Key findings from the MajesTEC-9 study include:^1,2

• There were 296 patients assigned to teclistamab and 297 to one of the combinations. The median (range) age was 70 (34–86) and the number of prior lines of therapy was 2 (1-3). Eighty percent were refractory to lenalidomide and 85% to anti-CD38 therapy; 92% were refractory to their last line of therapy.
• At the interim analysis, with a median follow-up of 17.3 months, teclistamab significantly improved PFS compared with the combinations, with an estimated 18-month PFS of 69.8% vs 26.9% (HR for disease progression or death, 0.29; 95% CI, 0.23-0.38; P < .001).
• The share of patients with a CR or better was higher with teclistamab than with the combinations (65.9% vs 16.8%; P < .001). OS was improved with teclistamab as compared with PVd or Kd, with an estimated 18-month OS comparison of 79.2% vs 68.6% (HR for death, 0.60; 95% CI, 0.43-0.83; P = 0002).
• AEs of grade 3 or 4 occurred in 84.9% of teclistamab recipients and in 76.3% of the PVd/Kd recipients. Deaths were seen in 6.5% and 3.5% of the teclistamab and combination groups, respectively; the majority were due to infections.
• Cytokine release syndrome, mostly grade 1 or 2, occurred in 66.0% of teclistamab recipients, and immune effector cell–associated neurotoxicity syndrome occurred in 4.1%. Grade 3 or 4 infection occurred in 41.6% of teclistamab recipients and in 29.0% of recipients treated with a combination.

“After the recent approval of [teclistamab plus subcutaneous daratumumab], a potential new standard of care, these results add to the growing body of evidence reinforcing the clinical power of [teclistamab] earlier in the treatment paradigm," Yusri Elsayed, MD, MHSC, PhD, global therapeutic area head, Oncology, Johnson & Johnson, said in the statement. “These findings further demonstrate how we're leading in multiple myeloma as we bring new options to better match the right therapy to the right patient at each stage of disease.”

The study was funded by Johnson & Johnson.

References

1. Mina R, Touzeau C, Hungria V, et al. MajesTEC-9: a phase 3 randomized 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):Abstr 7507. doi:10.1200/JCO.2026.44.16_suppl.7507
2. Touzeau C, Mina R, Quach H, et al; MajesTEC-9 Trial Investigators. Teclistamab in multiple myeloma with one to three previous lines of therapy. N Engl J Med. Published May 29, 2026. doi:10.1056/NEJMoa2603870
3. Johnson & Johnson announces US FDA approval of Tecvayli plus Darzalex Faspro for relapsed refractory multiple myeloma offering a potential new standard of care as early as second line. News release. Johnson & Johnson. March 5, 2026. Accessed May 29, 2026. https://www.jnj.com/media-center/press-releases/johnson-johnson-announces-u-s-fda-approval-of-tecvayli-plus-darzalex-faspro-for-relapsed-refractory-multiple-myeloma-offering-a-potential-new-standard-of-care-as-early-as-second-line