Tec-Dara Closes Survival Gap in High-Risk MM: Rahul Banerjee, MD

In a subgroup analysis of the phase 3 MajesTEC-3 trial (NCT05083169), teclistamab plus daratumumab (Tec-Dara) produced a 3-year progression-free survival (PFS) rate of 77% in patients with functional high-risk relapsed or refractory multiple myeloma (R/R MM) compared with 0% among those receiving standard treatment. Lead investigator Rahul Banerjee, MD, FACP, Fred Hutch Cancer Center, discussed these findings in an interview with The American Journal of Managed Care^® (AJMC^®) at the European Hematology Association (EHA) 2026 Congress.

The analysis, presented by Banerjee at the conference, builds on data that supported the FDA’s 2026 approval of teclistamab (Tecvayli; Janssen Biotech) plus daratumumab and hyaluronidase-fihj (Darzalex Faspro; Janssen Biotech) for R/R MM in earlier-line settings. It examined whether Tec-Dara could overcome the historically poor outcomes seen in 2 treatment-resistant populations: patients with high-risk cytogenetic abnormalities and those with functional high-risk disease. Banerjee noted that responses appeared to plateau after approximately 2 years, suggesting the potential for durable disease control not typically seen with other therapies in this setting.

This interview was lightly edited for clarity.

AJMC: Can you first provide an overview of the phase 3 MajesTEC-3 trial and its results?

Banerjee: The MajesTEC-3 trial led to the FDA approval of teclistamab, a BCMA [B-cell maturation antigen]–binding bispecific antibody, in earlier lines of treatment in myeloma. To put that all out in more detail, BCMA-binding bispecific antibodies basically are T cell–engaging drugs [that] bind a protein called BCMA on the myeloma cell, they bind a protein called CD3 on the T cell, and they make the T cell basically drop what it’s doing and attack the myeloma cell instead. They already had worked quite well in later lines of treatment based on single-arm data. The MajesTEC-3 trial [randomly assigned] patients to receive teclistamab plus daratumumab, what I’ll call Tec-Dara, vs standard treatment options like Dara-pomalidomide [Dara-Pd]. The idea for Tec-Dara is that daratumumab is a CD38 monoclonal antibody commonly used in myeloma. All of my patients have received it. Here, the idea is that the Dara is adding not just some myeloma activity, but [it has] also…been known to get rid of regulatory T cells. Basically, if you get rid of the regulatory T cells that are the brakes of your T cells, your other T cells can do the job and work [better] with teclistamab…to knock out the myeloma.

The data from the MajesTEC-3 trial, we knew, were amazing. Basically…at the 3-year mark, 83% of patients were still in remission, which is phenomenal. We don’t see [those] data ever in the relapsed myeloma setting—not even with chimeric antigen receptor [CAR] T-cell therapy, to be honest; [those] data were presented and published in December. We’re so impressed that the FDA approved it barely 3 months later. I’ve already been giving patients Tec-Dara in my own practice. But what we didn’t know, and what we sought to look at in the subgroup analysis [that was] presented here at the EHA meeting in Stockholm, [Sweden], is, how do patients with high-risk cytogenetics or functional high-risk disease biology—basically patients whom, historically, whatever new treatment we give doesn’t work for as well—in the era of Tec-Dara, do those mantras that these patients don’t do as well still hold true?

AJMC: Can you elaborate on what these subgroup analyses aimed to add to the understanding of the trial results? Which patient populations were evaluated, and why are they clinically important?

Banerjee: High-risk disease biology is traditionally defined as a number of chromosomal abnormalities on fluorescence in situ hybridization testing. For example, deletion 17p [del17p] is the one that almost anyone across hematology/oncology will have heard [of]. 17p is the guardian angel of the genome, and when it’s missing on the myeloma cells, those cells are inherently more deranged. They’re more resistant. Historically, patients with del17p, just as an example, you get them into remission, but it’s hard to keep them in remission. They have relapses earlier, [and we] have to keep giving them more and more treatments to keep them in remission, and they don’t do as well. That was one important subgroup where you know that these patients don’t do as well in the relapse setting. Can Tec-Dara close that gap? We want to answer the question.

All of these cytogenetic high-risk features are designed to predict the risk of early relapse. We now have a [term] for early relapse in myeloma: functional high-risk disease biology. The idea is that, for whatever reason, these patients…relapse much earlier than expected. For someone getting a triplet induction regimen, that’s typically defined as relapse within 18 months of starting and/or transplant if you got transplant. For someone getting a quadruplet induction regimen, that’s typically defined as relapse within 36 months, [or] 3 years, of starting treatment or transplant. The idea is that most of my patients diagnosed today, I tell them to expect at least 3 to 5 years of mileage, if not more, out of any given line of treatment. If they relapse earlier, that’s a problem.

Bottom line…we’d have to look at…both the cytogenetic high-risk and the functional high-risk [subgroups]. Historically, patients with functional high-risk myeloma, their overall survival is often less than 2 years, meaning that the first treatment didn’t work very well, and then all the subsequent treatments work progressively worse and worse…or just stop working, period. Again, the question is: Can Tec-Dara close that gap?

AJMC: The estimated 36-month PFS rates were higher across the Tec-Dara subgroups. What do these findings suggest about the potential role of Tec-Dara compared with existing treatment approaches in these populations?

Banerjee: Tec-Dara basically doesn’t care—high risk, functional high risk, both, neither…standard risk. No matter how you slice and dice the data, Tec-Dara performed very impressively…. As one example, when we looked at the patient with functional high-risk disease biology, of the patients who got standard treatments—treatments I used to give my patients all the time, like Dara-Pd—0% of the patients were still in remission 3 years out. Three-year PFS was 0%. Of the patients who got Tec-Dara, it was 77%, which is phenomenal. Again, this is a night-and-day difference here. Basically, Tec-Dara gives these patients a fighting chance at a deep and durable response across the board.

I think the nice thing about Tec-Dara from MajesTEC-3 is we already have 3 years of follow-up, and we’re starting to see a plateau, meaning…if you have maintained a response for 2-plus years on Tec-Dara, the odds of a further relapse are quite unlikely…. Tec-Dara is not like CAR T. You still remain on treatment, but you’re basically approaching what some people will call a functional cure, where you’re on treatment, but the myeloma is not going to come back. Obviously, we need more follow-up to say that, but especially for functional high risk, you don’t see that with any other treatment. Even with [MajesTEC-9 (NCT05572515)]…you don’t see that level of patients holding the line for years and years. With Tec-Dara, that very well may be possible.