Immunotherapy combination of teclistamab and daratumumab heralded as potential 'functional cure' for multiple myeloma | ASH 2025

Strong positive results of a novel combination of two immunotherapy drugs as a treatment for multiple myeloma after other treatments have failed suggest the combination could be a “functional cure,” the trial’s lead investigator said at the annual meeting of the American Society of Hematology (ASH) on Monday.

At a press briefing about a selection of high-profile, late-breaking abstracts, Maria-Victoria Mateos, M.D., Ph.D., shared data showing that patients treated with the combination of teclistamab and daratumumab had a progression-free survival rate (PFS) of 83.4% after three years of follow-up.

“You have to know that this is the greatest PFS treatment effect we have seen to date,” said Mateos, a hematologist at the University of Salamanca in Spain, at the briefing. The impressive PFS rate, combined with data showing that the PFS and overall survival rate were stable after six months of treatment, “suggest a potential for functional cure,” she said.

The moderator of the press briefing, Surbhi Sidani, M.D., echoed Mateos’ optimism but added caveats about infection rates and how the combination will fit into current clinical practice now that many patients are treated early on with other combinations that include daratumumab.

“The efficacy is truly remarkable with this combination,” said Sidani, who was one of the investigators that led the trial, dubbed MajesTEC-3, of the teclistamab-daratumumab combination. Speaking about the overall progress in multiple myeloma treatment in recent years, Sidani, a myeloma specialist, said, “We can see a light at the end of our tunnel with all of these therapies for our patients, for myeloma, for having maybe a functional cure in the future.”

Although chimeric antigen receptor T cell therapy has the advantage of being a one-time infusion, Mateos said the teclistamab-daratumumab combination, or “tec-dara” as it is being called, may be more practical for patients treated by community oncologists in the U.S. and at small hospitals in Europe. Patient preferences have to be factored in into sequencing, she said, and “based on these results, I can envision maybe some or many patients will not require subsequent lines of therapy.

The trial results showed a relatively high rate of serious infection during the first six months of tec-dara treatment. Mateos said that risk can be lowered with prophylactic use of antiviral and other antimicrobial medications and immunoglobulin replacement therapy.

Teclistamab, approved by the FDA in 2022 and sold under the brand name Tecvayli, is one of a number of FDA-approved bispecific antibodies that bind both (thus the name “bispecific”) to antigens on the surface of cancer cells and to surface markers on the T cells. By bringing the cancer cell and T cells together, the joint binding of the bispecific antibody activates T cells to kill the cancer cells. Teclistamab

binds to the CD3 receptor on T cells and to the B-cell maturation antigen (BCMA) on the surface of myeloma cells as well as on some healthy B-lineage cells. Daratumumab, sold under the brand name Darzalex, is a widely used monoclonal antibody that attaches to the CD38 protein of myeloma cells, killing them directly but also recruiting T cells to attack them. Mateos said that daratumumab works synergistically with teclistamab by expanding the number of T cells and creating a microenvironment that makes the teclistamab’s joint embrace of myeloma-T cell that much more effective.

The MajesTEC-3 trial enrolled 587 patients whose multiple myeloma had advanced despite treatment with one to three prior lines of therapy. The researchers randomly assigned half of the patients to the tec-dara combination and half to the standard of care for patients with multiple myeloma that has stopped responding to treatment, referred to by specialists as relapsed/refractory multiple myeloma (RRMM). The standard-of-care treatments were either daratumumab along with pomalidomide and dexamethasone or daratumumab along with bortezomib and dexamethasone.

The first two treatments with tec-dara were delivered weekly, the next three every other week, and the subsequent treatments, monthly. Mateos noted that the steroids were not necessary after the first treatment with tec-dara, an aspect of the regimen that the patients saw as a distinct advantage.

The PFS rate among the patients in the standard-of-care group was 29.7% after three years in contrast to the 83.4% rate among the patients in the tec-dara group, according to the abstract summarizing the study results. The overall survival rate was 83.3% in the tec-dara group compared with 65% in the standard-of-care group, and there were 45 deaths due to multiple myeloma progressing in the tec-dara group compared with 96 in the standard-of-care group. The abstract reports favorable results for tec-dara on other end points commonly used in cancer clinical trials, such as overall response and complete response. Moreover, the PFS benefit was seen in a range of subgroups, including in patients ages 75 and older. However, the results showed a higher rate of serious treatment-emergent adverse events in the tec-dara group compared with those in the standard-of-care group (70.7% vs. 62.45) and serious infections (54.1% vs. 43.4%). The abstract says that the infections decreased over time as the tec-dara dosing moved into a monthly schedule and with prophylactic measures taken.

“Dr. Mateos very nicely showed that the infection risk can be mitigated, but still, patients do get some infections, and we have to be very, very vigilant, especially as we transition these drugs to the community where doctors are treating many different diseases,” said Sidani.