Johnson & Johnson (J&J) announced new data from the phase 3 MajesTEC-3 trial showing that teclistamab-cqyv (Tecvayli) plus daratumumab and hyaluronidase-fihj (Darzalex Faspro) sustained disease control and survival in patients with relapsed or refractory multiple myeloma (RRMM) who had received 1 to 3 prior lines of therapy, the company announced September 23, 2026.¹ Using a relative survival mixture cure model applied to trial data, statistical modeling estimated that approximately 87% of patients treated with the combination may experience mortality risk and life expectancy similar to an age-matched general population.¹
Key facts
- Drugs: Teclistamab-cqyv (Tecvayli) + daratumumab/hyaluronidase-fihj (Darzalex Faspro); Johnson & Johnson
- Class: BCMA-directed bispecific antibody + CD38-directed antibody combination
- Indication: Relapsed/refractory multiple myeloma (RRMM), 1-3 prior lines
- Trial: Phase 3 MajesTEC-3 (NCT05083169); n=291 (combo) vs n=296 (DPd/DVd)
- Key modeling result: 86.6% cure fraction (combo) vs 0% (DPd/DVd); 18.5 vs 4.9 years life expectancy
- Key clinical result: 90% reduction in disease progression risk at 36 months
- Key clinical result: 83.3% vs 65.0% overall survival at 36 months (HR=0.46)
- Safety note: No significant difference in non-relapse mortality between arms
- Regulatory status: FDA approved March 2026; EC approved August 2026 (both as early as 2nd line)
- Disease burden: 2nd most common blood cancer; 180,000+ new cases/year; 59.8% 5-year survival
"These findings underscore how consequential treatment choice at first relapse can be in shaping a patient's long-term trajectory," said Luciano J. Costa, MD, PhD, professor of multiple myeloma and director of the Multiple Myeloma Research and Treatment Program at the University of Alabama at Birmingham, in a company press release.¹ "The sustained disease control observed with [Tecvayli] plus [Darzalex] [Faspro] is changing expectations for what treatment can achieve in relapsed or refractory multiple myeloma."
What did the mixture cure model show?
The analysis applied a relative survival mixture cure model to patients treated with teclistamab-cqyv plus daratumumab and hyaluronidase-fihj (n=291) and the standard-of-care comparator, daratumumab plus pomalidomide/dexamethasone or bortezomib/dexamethasone (DPd/DVd; n=296), to assess whether long-term disease control could approach outcomes seen in the general population.¹ Best-fit models estimated a cure fraction of 86.6% (95% confidence interval [CI], 81-91) for overall survival with the combination, compared with 0% (95% CI, 0-53) for DPd/DVd.¹ Modeled remaining life expectancy was 18.5 years with the combination, compared with 4.9 years for DPd/DVd and 21.1 years for the matched general population.¹
What did the post hoc analysis of disease progression show?
A separate post hoc analysis found that teclistamab-cqyv plus daratumumab and hyaluronidase-fihj reduced the cumulative incidence of disease progression at 36 months to 8.7%, compared with 62.1% for DPd/DVd, a 90% reduction in progression risk (subdistribution hazard ratio, 0.10; 95% CI, 0.07-0.16; P<.0001).¹ The 36-month overall survival rate was 83.3% with the combination compared with 65.0% for DPd/DVd (hazard ratio, 0.46; 95% CI, 0.32-0.65; P<.0001), while non-relapse mortality did not differ significantly between arms (10.2% vs 9.0%; P=.5668).¹ Both analyses (Abstracts OA-58 and OA-49) will be presented at the International Myeloma Society Annual Meeting.¹
What did J&J say about the findings?
"Our ambition is to build on this progress by fundamentally changing the long-term trajectory of multiple myeloma and, ultimately, creating a future in which this disease is no longer defined as incurable," said Yusri Elsayed, MD, MHSc, PhD, global therapeutic area head of oncology at Johnson & Johnson Innovative Medicine, in the release.¹
Why is multiple myeloma significant, and what's next?
Multiple myeloma is the second most common blood cancer worldwide, with more than 180,000 new cases diagnosed globally each year and a 5-year survival rate of 59.8%.¹ Overall survival in multiple myeloma has improved substantially in recent decades, evolving from a diagnosis measured in a few years to one where effective treatment options now exist across every stage and line of therapy.¹,² The combination was approved by FDA in March 2026 for patients with RRMM who have received at least 1 prior line of therapy and by the European Commission in August 2026 for the same population. The MajesTEC-3 trial is ongoing and continued follow-up will assess whether observed outcomes confirm these model-based predictions, according to the company.¹
What are the limitations?
The mixture cure model's projections, including the 87% cure fraction estimate, are statistical extrapolations from trial data rather than confirmed long-term outcomes, and the DPd/DVd comparator arm's cure-fraction estimate carried substantially greater statistical uncertainty. These findings have been presented as conference abstracts and have not yet undergone full peer review or journal publication.
References
- Johnson & Johnson. New model-based analysis further supports the potential of TECVAYLI (teclistamab-cqyv) plus DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) to redefine long-term survival expectations in early line relapsed/refractory multiple myeloma. Press release. Published September 23, 2026. Accessed September 24, 2026. https://www.jnj.com/media-center/press-releases/new-model-based-analysis-further-supports-the-potential-of-tecvayli-teclistamab-cqyv-plus-darzalex-faspro-daratumumab-and-hyaluronidase-fihj-to-redefine-long-term-survival-expectations-in-early-line-relapsed-refractory-multiple-myeloma
- Kazandjian D. Multiple myeloma epidemiology and survival: a unique malignancy. Semin Oncol. 2016;43(6):676-681. doi:10.1053/j.seminoncol.2016.11.004
