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Teclistamab is associated with better progression-free (PFS) and overall survival (OS) than standard regimens for relapsed or refractory multiple myeloma, according to the results of the first phase 3 trial to evaluate the B-cell maturation antigen (BCMA) bispecific antibody as a monotherapy.

In the MajesTEC-9 trial, teclistamab reduced the risk for progression or death by 71% and the risk for death by 40%, reported study author Roberto Mina, MD, while presenting the results in an oral abstract session at the American Society of Clinical Oncology (ASCO) 2026 annual meeting in Chicago. The findings were simultaneously published in the New England Journal of Medicine.

These results, considered alongside findings from MajesTEC-3 , support teclistamab-based therapy as a new standard of care from the second line onward, including in cases that are refractory to anti-CD38 antibodies and lenalidomide, said Mina, from Emory University’s Winship Cancer Institute in Atlanta.

Although newly diagnosed multiple myeloma outcomes have improved over the years with the introduction of triplet and quadruplet regimens, options remain limited for cases that become resistant to anti-CD38 antibodies and lenalidomide, according to the abstract.

Teclistamab, already approved for heavily pretreated multiple myeloma, could offer an earlier option for such cases, based on promising results from the MajesTEC-3 study, which evaluated the agent in combination with daratumumab.

The present study aimed to determine if similar results could be achieved using teclistamab alone.

Trial Design

MajesTEC-9 involved 593 patients with relapsed or refractory multiple myeloma who had received 1-3 prior lines, including an anti-CD38 antibody and lenalidomide. Participants were randomly assigned 1:1 to receive teclistamab (n = 296) or investigator's choice of pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd) (n = 297).

Teclistamab was given in step-up doses followed by weekly dosing, then less frequent maintenance doses based on response. 

The primary endpoint was PFS. Secondary endpoints included OS, complete response or better, and safety.

The population had a median age of 70 years with a median of two prior lines of therapy. Most cases were refractory to both lenalidomide (80%) and anti-CD38 therapy (85%), and 92% were refractory to their most recent line of therapy.

Survival Outcomes and Safety

After a median follow-up of 17.3 months, teclistamab was associated with a 71% reduced risk for progression or death compared with standard regimens (hazard ratio [HR], 0.29; P < .0001). Median PFS was not reached in the teclistamab group, versus 8.2 months for standard of care. The 18-month PFS rates also favored teclistamab (69.8% vs 26.9%). PFS benefits were maintained across prespecified subgroups, including anti-CD38- and lenalidomide-refractory patients.

Similarly, OS was significantly better in the teclistamab group than the standard-care group (HR, 0.60; P = .0020), even though more than two-thirds of the patients in the latter cohort who went on to subsequent treatment received a bispecific antibody or CAR T-cell therapy.

The rate of complete response or better was 65.9% for teclistamab vs 16.8% for standard regimens.

Grade 3 or 4 adverse events were more frequent with teclistamab than standard regimens (84.9% vs 76.3%), including grade 3 or 4 infections (41.6% vs 29%); however, the median treatment duration was nearly double with teclistamab. 

Infection risk was highest during the first 6 months, then decreased over time, which Mina attributed to better disease control and the switch to monthly dosing. Most infection-related deaths occurred within the first 6 months. Of the 16 such deaths in the teclistamab group, 8 occurred in patients with low immunoglobulin levels and 5 occurred in patients who had received no immunoglobulin replacement.

Clinicians administering teclistamab need to be “very vigilant, particularly at the beginning of treatment, and rigorous with immunoglobulin replacement therapy and antimicrobial prophylaxis,” Mina said.

Cytokine release syndrome occurred in 66% of teclistamab-treated patients, although these instances were mostly low grade. Immune effector cell-associated neurotoxicity occurred in 4.1% of patients in the teclistamab group.

Finding a Place for Monotherapy

Ajai Chari, MD, of the University of California San Francisco, who was not involved in the study, said the choice between teclistamab alone vs teclistamab/daratumumab combination therapy depends on a patient’s history with daratumumab.

For daratumumab-refractory patients, “the answer is clear,” Chari said during a panel discussion: they should receive teclistamab monotherapy.

But the picture is murkier for patients who have been exposed to daratumumab but are not yet refractory to it, he added.

It is “unclear how much [daratumumab] exposure will matter” before re-treating, Chari said. 

Complicating matters, the two pivotal trials enrolled populations with distinct treatment histories, he said, noting that fewer than 5% of patients enrolled in MajesTEC-3 had received prior anti-CD38 therapy, vs all patients in MajesTEC-9.

The panel session also weighed the trial’s comparator after an audience member questioned why teclistamab was tested against a doublet, carfilzomib/dexamethasone, rather than a more modern triplet. 

These MajesTEC studies were designed years ago, Chari replied, when a doublet comparator was the norm. “So I think this is what we’re learning, and we’re always trying to catch up,” he said.

The discussion also brought up another open question: How long should teclistamab treatment continue, since patients in both MajesTEC trials were treated until disease progression?

“Hopefully not until progression,” Mina said. “But I would like to be cautious suggesting early discontinuation, because the good results we’ve seen were not with early discontinuation.”

The question deserves a randomized trial of its own, Mina concluded.

MajesTEC-9 was funded by Johnson & Johnson. Mina disclosed relationships with Johnson & Johnson, Pfizer, Sanofi, and others; several co-authors are employees of Johnson & Johnson. Chari disclosed relationships with Janssen, AbbVie, AstraZeneca, and others.