TECVAYLI plus DARZALEX FASPRO showed sustained survival and lower progression risk in relapsed/refractory multiple myeloma in the Phase 3 MajesTEC-3 study.
Written By: Charvi Kalal, PharmD
Reviewed By: Pharmacally Editorial Team
Johnson & Johnson reported new analyses from the Phase 3 MajesTEC-3 study evaluating TECVAYLI® (teclistamab-cqyv) plus DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) in patients with relapsed or refractory multiple myeloma who had received one to three prior lines of therapy. The analyses assessed long-term survival, disease progression and non-relapse mortality versus investigator’s choice of daratumumab plus pomalidomide and dexamethasone (DPd) or daratumumab plus bortezomib and dexamethasone (DVd).
A model-based analysis estimated an overall-survival cure fraction of 86.6% with TECVAYLI plus DARZALEX FASPRO, while a separate post hoc analysis showed a 90% reduction in the risk of disease progression versus DPd/DVd.
Model projects long-term survival
A relative survival mixture cure model included 291 patients receiving TECVAYLI plus daratumumab and 296 receiving DPd/DVd. The estimated overall-survival cure fraction was 86.6% (95% CI, 81–91) with the TECVAYLI-based combination versus 0% (95% CI, 0–53) with DPd/DVd, although the comparator estimate had greater uncertainty.
Projected remaining life expectancy was 18.5 years with TECVAYLI plus DARZALEX FASPRO versus 4.9 years with DPd/DVd and 21.1 years in the matched general population. These are model-based projections rather than observed lifetime outcomes.
Lower progression associated with improved survival
At 36 months, the cumulative incidence of disease progression was 8.7% with TECVAYLI plus DARZALEX FASPRO versus 62.1% with DPd/DVd, corresponding to a 90% reduction in progression risk (sHR, 0.10; 95% CI, 0.07–0.16; P<0.0001).
Overall survival at 36 months was 83.3% versus 65.0%, respectively, with a hazard ratio for death of 0.46 (95% CI, 0.32–0.65; P<0.0001).
Non-relapse mortality did not differ significantly between groups. At 36 months, non-relapse mortality was 10.2% with TECVAYLI plus DARZALEX FASPRO and 9.0% with DPd/DVd (sHR, 1.16; 95% CI, 0.69–1.98; P=0.5668).
Survival benefit emerged after 10 months
Overall survival did not differ between groups during the first 10 months (HR, 1.08; 95% CI, 0.64–1.81). After 10 months, the risk of death was 78% lower with TECVAYLI plus DARZALEX FASPRO (HR, 0.22; 95% CI, 0.13–0.38).
A prespecified restricted mean survival time analysis showed a statistically significant 2.15-month overall-survival difference during the period analyzed (P=0.0088).
MajesTEC-3 evaluates earlier-line treatment
MajesTEC-3 is an ongoing Phase 3 randomized study evaluating teclistamab plus subcutaneous daratumumab versus investigator’s choice of DPd or DVd in patients with relapsed/refractory multiple myeloma after one to three prior lines of therapy. The primary endpoint is progression-free survival, with secondary endpoints including complete response or better, overall response rate, minimal residual disease negativity, overall survival and safety.
TECVAYLI is a bispecific T-cell engager targeting CD3 on T cells and BCMA on multiple myeloma cells. DARZALEX FASPRO combines the CD38-directed antibody daratumumab with recombinant human hyaluronidase PH20 for subcutaneous administration.
Safety remains important
TECVAYLI carries boxed warnings for cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS). Across clinical trials, CRS occurred in 64% of patients and neurologic toxicity in 60% at the recommended dosage, with Grade 3/4 neurologic toxicity reported in 6%.
In MajesTEC-3, ICANS occurred in 1.1% of patients receiving TECVAYLI with daratumumab and hyaluronidase-fihj, including one Grade 4 event. Other important risks include serious infections, hepatotoxicity, neutropenia, hypogammaglobulinemia, hypersensitivity and administration-related reactions.
DARZALEX FASPRO is also associated with administration-related reactions, infections, neutropenia and thrombocytopenia. Daratumumab can interfere with indirect antiglobulin testing and blood compatibility testing.
Long-term outcomes remain under evaluation
The MajesTEC-3 analyses showed sustained disease control and improved overall survival with TECVAYLI plus DARZALEX FASPRO compared with DPd/DVd, without a statistically significant difference in non-relapse mortality.
The mixture cure model provides projected long-term survival estimates rather than observed lifetime outcomes. Continued follow-up will determine whether these projections are supported by subsequent clinical data.
The findings will be presented at the 2026 International Myeloma Society Annual Meeting in Glasgow, UK.
Reference
Effelterre T, et al. (2026). Projecting functional cure in patients (Pts) with relapsed/refractory multiple myeloma (RRMM) in the MajesTEC-3 study of teclistamab-daratumumab (Tec-Dara) using a mixture cure model. Presented at: The 2026 International Myeloma Society (IMS) Annual Meeting; September 23, 2026; Glasgow, UK.
Costa L, et al. (2026). Overall survival, progression and non-relapse mortality with teclistamab plus daratumumab (Tec-Dara) vs Dara-based triplets in relapsed/refractory multiple myeloma (RRMM): MajesTEC-3 post hoc analysis. Presented at: The 2026 International Myeloma Society (IMS) Annual Meeting; September 24, 2026; Glasgow, UK.
MajesTEC-3, NCT05083169. (2026). A Phase 3 randomized study comparing teclistamab + subcutaneous daratumumab (Tec-Dara) versus daratumumab SC + pomalidomide + dexamethasone (DPd) or daratumumab SC + bortezomib + dexamethasone (DVd). ClinicalTrials.gov.
Johnson & Johnson. (2026). New model-based analysis further supports the potential of TECVAYLI® plus DARZALEX FASPRO® to redefine long-term survival expectations in early-line relapsed/refractory multiple myeloma. Johnson & Johnson, September 23, 2026.
About the Writer
Charvi Kalal (LinkedIn) is a Pharm.D intern and aspiring medical writer with hands-on experience in medical writing, clinical research, pharmacovigilance, and clinical pharmacy. She has experience in medical content writing through CliMed, along with exposure to ADR monitoring, prescription analysis, patient counselling, literature review, and research documentation. Her research focuses on ADR monitoring and reporting in breast cancer patients receiving targeted therapy. With certifications in GCP, biomedical research, scientific writing, and clinical research, she is passionate about transforming scientific evidence into accurate, engaging, and accessible healthcare content.