Dr Krishnan on Implications of the FDA Approval of Daratumumab/Teclistamab in R/R Myeloma

[Daratumumab plus teclistamab] offers us another very potent choice for patients at first relapse. But again, it sort of speaks to the idea of having a long-term picture of how you are going to treat patients. For patients [for whom] you have no intent to [give CAR T-cell therapy], I think this is probably the preferable regimen because one can anticipate a long remission.

Amrita Krishnan, MD, the Nason-Hollingsworth Chair in Multiple Myeloma, executive medical director of Hematology at City of Hope Orange County, director of the Judy and Bernard Briskin Multiple Myeloma Center, and professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope, discussed the significance of the FDA approval of teclistamab-cqyv (Tecvayli) in combination with daratumumab and hyaluronidase-fihj (Darzalex Faspro) for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 1 prior line of therapy.

The March 2026 regulatory decision was supported by data from the phase 3 MajesTEC-3 trial (NCT05083169). Findings demonstrated that patients treated with teclistamab plus daratumumab (n = 291) experienced a median progression-free survival (PFS) that was not reached (NR; 95% CI, not evaluable [NE]-NE) compared with 18.1 months (95% CI, 14.6-22.8) for those given investigator’s choice of daratumumab plus pomalidomide (Pomalyst) and dexamethasone (DPd) or daratumumab plus bortezomib (Velcade) and dexamethasone (DVd; n = 296; HR, 0.17; 95% CI, 0.12-0.23; P < .0001). The median overall survival was NR (95% CI, NE-NE) in the teclistamab arm vs NR (95% CI, 41.4-NE) in the control arm (HR, 0.46; 95% CI, 0.32-0.65; P < .0001).

With the daratumumab plus teclistamab now approved following first-line therapy, Krishnan explained this regimen could impact sequencing considerations for patients following first relapse, particularly for those who do not plan to receive CAR T-cell therapy in the second or later lines of therapy.

Although teclistamab represents a potent BCMA-directed strategy at first relapse, Krishnan noted that one key remaining question centers around patients who were previously exposed to an anti-CD38 agent such as daratumumab and those who are anti-CD38 refractory. Within MajesTEC-3, Krishnan explained that the majority of patients were not previously exposed to anti-CD38 agents or anti-CD38 refractory. Further understanding if this subset of anti-CD38–exposed patients can derive the same benefit will be crucial; Krishnan explained that in the MajesTEC-3 regimen, daratumumab is used for its effects on immune cells as well as myeloma cells, augmenting the effects of teclistamab.

Krishnan concluded by noting that this approval offers another potent treatment choice for patients at first relapse, and it underscores the importance of long-term treatment planning for patients with multiple myeloma.