Teclistamab Combo Approved by FDA for R/R MM

Teclistamab (Tecvayli) plus daratumumab and hyaluronidase-fihj (Darzalex Faspro), both from Janssen Biotech, Inc, has received approval from the FDA to treat patients with relapsed or refractory multiple myeloma (R/R MM) in early-line settings.¹ It could come as early as in the second line for patients who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent.

“The option to use this regimen as early as second line is particularly important because patients with RR MM often experience multiple relapses and reduced responsiveness to therapy over time, which makes earlier treatment with the most effective therapies critical,” said Luciano Costa, MD, primary investigator of MajesTEC-3 and director of the Multiple Myeloma Research and Treatment Program, University of Alabama at Birmingham, in a statement. “In addition, the steroid-sparing approach may reduce toxicity and improve tolerability.”²

This approval also converts the October 2022 accelerated approval of teclistamab as monotherapy to a full traditional approval for adult patients with R/R MM who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.^1,3 Teclistamab targets B-cell maturation antigen, expressed on myeloma cells, and the CD3 receptor expressed on T cells. It was the first bispecific antibody ever approved back in 2022, marking a novel class of medications; there are now 15 bispecific antibodies approved by the FDA.⁴

The approval is also the third approval handed down through the FDA Commissioner’s National Priority Review Voucher pilot program, following on the heels of zongertinib (Hernexeos; Boehringer Ingelheim Pharmaceuticals, Inc) approved in February to treat HER2-mutant nonsquamous non–⁠small cell lung cancer.^1,5 It also means that daratumumab and hyaluronidase-fihj now has 6 FDA-approved indications, following an approval in January for newly diagnosed MM.⁶

Data from the phase 3 open-label, multicenter, ongoing MajesTEC-3 trial (NCT05083169) support this new approval. In the trial, patients (N = 587) were randomized 1:1 to receive either subcutaneous teclistamab-daratumumab (n = 291) or investigator’s choice of daratumumab, pomalidomide (Pomalyst), and dexamethasone (DPd) or daratumumab, bortezomib (Velcade), and dexamethasone (DVd) (n = 296).¹

The clinical benefit of the combination is clear.² The primary outcome of interest was progression-free survival, and at 3 years, this rate was 83% in the treatment arm of MajesTEC-3 (HR, 0.17; 95% CI, 0.12-0.23; P < .0001) compared with 30% in the investigator’s choice arm (the control arm). The findings of key secondary outcomes trended similarly, also evaluated at 3 years:

• Overall response: 89.0% vs 75.3%, respectively (OR, 2.65; 95% CI, 1.68-4.18)
• Complete response or better: 81.8% vs 32.1% (OR, 9.56; 95% CI, 6.47-14.14)
• Minimal residual disease negativity: 58.4% vs 17.1% (OR, 6.78; 95% CI, 4.53-10.15, P < .0001; evaluable rate of 89.3% vs 63.0%)

In addition, the overall survival rate was 28% greater in the treatment vs the control arm: 83.3% vs 65.0%.

However, the 2 arms had similar rates of overall grade 3/4 treatment-emergent adverse events (TEAEs), at 95.1% vs 96.6%, and of grade 5 TEAEs, at 7.1% and 5.9%. Drilling down, there were higher rates of any-grade and grade 3/4 infections in the teclistamab arm—96.5% and 54.1% vs 84.1% and 43.4%—but the grade 3 infections dropped after the first 6 months of treatment. Cytokine release syndrome was seen in 60.1%, but no patient required treatment discontinuation and all cases were grade 1 or 2. Overall, serious AEs were more common in the treated cohort vs the control cohort (70.7% vs 62.4%), but corresponding treatment discontinuation rates were low (4.6% and 5.5%).

Teclistamab is also being investigated in the ongoing phase 3 MajesTEC-9 trial (NCT05572515), with recent data showing a 71% reduced risk of disease progression or death and a 40% reduced risk of death vs standard-of-care treatments in patients who had received 1 to 3 prior lines of therapy.⁷

References

1. FDA approves teclistamab in combination with daratumumab hyaluronidase-fihj for relapsed or refractory multiple myeloma. News release. FDA. March 5, 2026. Accessed March 5, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-teclistamab-combination-daratumumab-hyaluronidase-fihj-relapsed-or-refractory-multiple
2. 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 March 5, 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
3. Mattina C. FDA approves first bispecific antibody, teclistamab, for R/R multiple myeloma. AJMC^®. October 26, 2022. Accessed March 5, 2026. https://www.ajmc.com/view/fda-approves-first-bispecific-antibody-teclistamab-for-r-r-multiple-myeloma
4. Pizzolato J. FDA approved bispecific antibodies. Evitria. September 23, 2025. Accessed March 5, 2026. https://www.evitria.com/journal/bispecific-antibodies/fda-approved-bispecific-antibodies/
5. McCormick B. FDA grants accelerated approval to zongertinib for HER2-mutant NSCLC. AJMC. February 26, 2026. Accessed March 5, 2026. https://www.ajmc.com/view/fda-grants-accelerated-approval-to-zongertinib-for-her2-mutant-nsclc
6. Shaw ML. FDA green-lights D-VRd quadruplet for newly diagnosed multiple myeloma. AJMC. January 27, 2026. Accessed March 5, 2026. https://www.ajmc.com/view/fda-greenlights-d-vrd-quadruplet-for-newly-diagnosed-multiple-myeloma
7. Shaw ML. MajesTEC-9 data add to accolades to teclistamab in multiple myeloma. AJMC. January 15, 2026. Accessed March 5, 2026. https://www.ajmc.com/view/majestec-9-data-add-to-accolades-for-teclistamab-in-multiple-myeloma