Teclistamab Reduces Risk of Progression or Death in Earlier-Line Multiple Myeloma

Teclistamab-cqyv (Tecvayli; Janssen Biotech, Inc) monotherapy significantly reduced the risk of disease progression or death and improved overall survival (OS) compared with investigator-selected standard regimens in patients with relapsed or refractory multiple myeloma (RRMM) who received 1 to 3 previous lines of therapy, according to interim findings from the phase 3 MajesTEC-9 trial (NCT05572515) published in The New England Journal of Medicine.^1,2

At a median follow-up of about 17.3 months, teclistamab reduced the risk of disease progression or death by approximately 71% compared with pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd; HR, 0.29; 95% CI, 0.23-0.38; P < .001). At 18 months, the estimated progression-free survival (PFS) rate was 69.8% with teclistamab compared with 26.9% with PVd or Kd. Median PFS was not reached with teclistamab and was 8.2 months in the control group.¹

MajesTEC-9 Evaluates Teclistamab Earlier in Treatment Course

The international, open-label phase 3 trial randomly assigned 593 patients to teclistamab (n = 296) or investigator’s choice of PVd or Kd (n = 297). Participants received 1 to 3 prior lines of antimyeloma therapy—including previous treatment with lenalidomide and an anti-CD38 monoclonal antibody—and either experienced disease progression or failed to respond to their most recent regimen. Prior B-cell maturation antigen (BCMA)–directed treatment was not permitted.^1,2

The median patient age was approximately 70 years, with approximately 29% of enrolled patients aged 75 or older. Patients had received a median of 2 prior treatment lines, and the population demonstrated substantial treatment resistance: 80% had lenalidomide-refractory disease, 85% were refractory to anti-CD38 therapy, and more than 90% were refractory to their most recent line of treatment.¹

Teclistamab is a bispecific antibody that simultaneously targets BCMA on myeloma cells and CD3 on T cells, redirecting T-cell activity toward malignant plasma cells.³ Earlier MajesTEC-1 findings established the activity of teclistamab in heavily pretreated RRMM, with an overall response rate of approximately 63%.⁴

Deep Responses Accompany Survival Benefit

In addition to improving PFS, teclistamab produced substantially deeper responses than the comparator regimens. A complete response or better occurred in 65.9% of patients receiving teclistamab, compared with 16.8% of patients receiving PVd or Kd (P < .001). Overall response rates were 84.5% and 54.2%, respectively.¹

Median duration of response was not reached in the teclistamab group compared with 13.4 months with PVd or Kd.¹

An OS benefit was also observed. The estimated 18-month OS rate was 79.2% with teclistamab compared with 68.6% with PVd or Kd, corresponding to a 40% reduction in the risk of death (HR, 0.60; 95% CI, 0.43-0.83; P = .002). Median OS had not been reached in either group at the interim analysis. Teclistamab also significantly delayed the worsening of multiple myeloma–associated symptoms.¹

Infection Risk Remains Central to Teclistamab Management

The efficacy benefit was accompanied by a higher burden of serious toxicity. Grade 3 or 4 adverse events (AEs) occurred in 84.9% of patients treated with teclistamab compared with 76.3% receiving PVd or Kd, and serious AEs occurred in 56.7% and 45.6%, respectively. Neutropenia was the most common grade 3 or 4 AE, affecting approximately 54.3% and 22.3% of patients, respectively.¹

Grade 3 or 4 infections occurred in 41.6% of teclistamab-treated patients compared with 29.0% of controls, and fatal infections occurred in 5.5% and 2.8%, respectively.¹ Investigators emphasized antimicrobial prophylaxis, infection surveillance, and immunoglobulin replacement when indicated. Current FDA labeling similarly warns that teclistamab can cause severe, life-threatening, or fatal infections.³

Cytokine release syndrome occurred in 66.0% of patients receiving teclistamab and was predominantly grade 1 or 2. Two patients experienced grade 3 events. Immune effector cell–associated neurotoxicity syndrome occurred in 4.1%, with most events at grade 1 or 2.¹

Role of BCMA-Directed Bispecific Therapy May Expand

Data from the randomized trial support using BCMA-directed bispecific therapy considerably earlier in the RRMM treatment course than teclistamab monotherapy is currently approved for in the US. Teclistamab is currently FDA approved as monotherapy after at least 4 prior lines of therapy and, in combination with daratumumab and hyaluronidase-fihj, after at least 1 prior line containing a proteasome inhibitor and immunomodulatory agent.³

MajesTEC-9 findings support further consideration of teclistamab monotherapy beginning as early as the first relapse but underscore the importance of infection prevention and monitoring when integrating bispecific antibodies earlier in treatment.¹

REFERENCES

1. Touzeau C, Mina R, Quach H, et al. Teclistamab in multiple myeloma with one to three previous lines of therapy. N Engl J Med. 2026;395(5):440-453. doi:10.1056/NEJMoa2603870

2. A study comparing teclistamab monotherapy versus pomalidomide, bortezomib, dexamethasone or carfilzomib, dexamethasone in participants with relapsed or refractory multiple myeloma (MajesTEC-9). ClinicalTrials.gov. Updated April 13, 2026. Accessed August 11, 2026. https://clinicaltrials.gov/study/NCT05572515

3. Tecvayli. Prescribing information. Janssen Biotech, Inc; 2024. Accessed August 11, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761291s008lbl.pdf

4. Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022;387(6):495-505. doi:10.1056/NEJMoa2203478

5. New Tecvayli data demonstrates superior progression-free and overall survival as early as first relapse in multiple myeloma. News release. Johnson & Johnson. May 29, 2026. Accessed August 11, 2026. https://www.jnj.com/media-center/press-releases/new-tecvayli-data-demonstrates-superior-progression-free-and-overall-survival-as-early-as-first-relapse-in-multiple-myeloma