Teclistamab-cqyv With Daratumumab and Hyaluronidase-fihj Improves Survival in Relapsed, Refractory MM

In the pivotal phase 3, randomized MajesTEC-3 study (NCT05083169), teclistamab (Tec, Tecvayli; Johnson & Johnson) plus daratumumab and hyaluronidase (Dara, Darzalex Faspro; Johnson & Johnson; Tec-Dara) significantly reduced the risk of disease progression or death in patients with relapsed/refractory multiple myeloma (RRMM) as early as the second line (2L) of treatment compared to standard regimens. The data were presented at the Late-Breaking Abstracts Session at the 67^th American Society of Hematology (ASH) Annual Meeting and Exposition and simultaneously published in The New England Journal of Medicine.^1-4

Key Efficacy End Points Met With Tec-Dara

The combination reduced the risk of disease progression or death by about 83.3% at 36 months of follow-up (hazard ratio [HR], 0.17; 95% CI, 0.12–0.23, P < .0001). Remarkably, over 90% of patients treated with Tec-Dara who were alive at 6 months were also alive at 30 months, a major sign of long-term efficacy.^1-3

There were significantly higher rates of complete responses or better (81.8% vs 32.1%, respectively; odds ratio [OR], 9.56; 95% CI, 6.47–14.14), overall response (89.0% vs 75.3%; OR, 2.65; 95% CI, 1.68–4.18), and minimal residual disease (MRD)-negativity (58.4% vs 17.1%; OR, 6.78; 95% CI, 4.53–10.15) observed with Tec-Dara (P < .0001), according to the investigators.^1-3

Compared with standard-of-care, patients treated with Tec-Dara remained symptom-free significantly longer, underscoring the major improvements in patient-reported quality of life with the treatment. Furthermore, at data cutoff—at which 71.0% of patients remained on Tec-Dara—median treatment duration was twice as long as Dara and dexamethasone with either pomalidomide or bortezomib (DPd/DVd; 32.4 vs 16.1 months).^1-3

“We consider that this synergistic immunotherapy combination based on teclistamab and daratumumab is a new potential standard of care for relapsed/refractory myeloma patients after at least 1 prior line of therapy, with broad potential across academic and community settings,” María-Victoria Mateos, MD, PhD, consultant physician in the hematology department and associate professor of medicine at Hospital Universitario de Salamanca, said during the late-breaking presentation.¹

Background on Teclistamab and Daratumumab With Hyaluronidase

The MajesTEC-3 study investigators evaluated the safety and efficacy of the combination of Tec-Dara versus DPd/DVd in patients with RRMM who have previously received 1 to 3 lines of prior therapy. Increasing rates of patient attrition and decreasing response durability with each line of RRMM therapy require novel, earlier approaches.¹

Teclistamab is a combinable BCMA-targeting bispecific antibody that redirects T-cells and has shown efficacy in RRMM, inducing deep, durable responses. Daratumumab is a foundational anti-CD38-targeting monoclonal antibody that has shown its own significant improvements in OS in newly diagnosed MM and RRMM. Together, the bispecific regimen has shown significant efficacy as soon as the 2L treatment, providing meaningful potential for future availability and proliferation of this treatment.^1,5,6

Safety Considerations Observed in MajesTEC-3

A notable safety trend was observed in a high frequency of grade 3 or higher treatment-emergent adverse events (TEAEs), though rates were comparable between the Tec-Dara and standard-of-care groups. Concurrently, any grade infections occurred in 96.5% and 84.1% of Tec-Dara and DPd/DVd patients, respectively; however, as noted by Mateos, new-onset grade 3 or higher infections decreased over time, which coincided with transitioning to dosing every 4 weeks.¹

“Infections were frequent in both arms; most of these infections were COVID-19, upper-respiratory tract infections, and COVID-19 pneumonia,” Mateos explained, noting that study protocol was amended to reinforce the diligent use of established prophylaxis and IgRT supplementation. “MajesTEC-3 started recruiting patients during the COVID-19 pandemic, but especially when we had no specific guidelines for the management of bispecific monoclonal antibodies.”¹

Responding to the positive data, the FDA granted Johnson & Johnson a breakthrough therapy designation for the regimen, which is expected to expedite the development and review of the medicine. Accordingly, Johnson & Johnson submitted a supplemental biologics license application for the use of Tec-Dara as a combination treatment in RRMM. If approved, the treatment would represent the continuation of a paradigm shift in the treatment of patients with cancer.³

“The combination of [teclistamab] and [daratumumab with hyaluronidase] offers remarkable efficacy, a well-characterized safety profile with robust infection management protocols,” Mateo said in a news release from Johnson & Johnson. “It has the potential to change the standard of care as a steroid-sparing combination regimen suited for outpatient administration on the familiar [daratumumab] schedule.”³

REFERENCES

1. Mateos M, Bahlis N, Perrot A, et al. Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or Bortezomib (DPd/DVd) in patients (Pts) with relapsed refractory multiple myeloma (RRMM): Results of majestec-3. Presented: 67^th ASH Annual Meeting and Exposition; December 9, 2025; Orlando, FL; Orange County Convention Center West Hall D2. Accessed Via ASH Virtual Platform on December 9, 2025. https://meetings-api.hematology.org/api/abstract/vmpreview/304640

2. Costa LJ, Bahlis NJ, Perrot A, et al. Teclistamab plus daratumumab in relapsed or refractory multiple myeloma. N Engl J Med. Published Online December 9, 2025. Accessed December 9, 2025. doi:10.1056/NEJMoa2514663

3. 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. News Release. Johnson & Johnson. Released December 9, 2025. Accessed December 9, 2025. 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

4. A study of teclistamab in combination with daratumumab subcutaneously (SC) (Tec-Dara) versus daratumumab SC, pomalidomide, and dexamethasone (DPd) or daratumumab SC, bortezomib, and dexamethasone (DVd) in participants with relapsed or refractory multiple myeloma (MajesTEC-3). ClinicalTrials.gov Identifier: NCT05083169. Last Updated December 5, 2025. Accessed December 9, 2025. https://clinicaltrials.gov/study/NCT05083169

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

6. Afrough A, Atrash S, Paul B, et al. Efficacy and Safety of Daratumumab, Pomalidomide, and Dexamethasone (DPd) Compared to Daratumumab, Bortezomib, and Dexamethasone (DVd) in Daratumumab-Naïve Relapsed Multiple Myeloma. Cancers (Basel). 2023;15(19):4894. doi:10.3390/cancers15194894