Consistent Safety Data Support Teclistamab/Daratumuamb in Myeloma

With the recent FDA approval of teclistamab (Tecvayli) plus daratumumab (Darzalex), more patients will be treated using bispecific T-cell engager (BiTE) therapy for early relapse of multiple myeloma. During a Case-Based Roundtable event for oncologists in the Chicago area, Patrick Hagen, MD, associate professor at Loyola Medicine in Melrose Park, Illinois, discussed the results of the MajesTEC-3 trial (NCT05083169) and how the safety profile of this regimen, though comparable to chimeric antigen receptor (CAR) T-cell therapy in some respects, tends to be more mild and offers a more convenient route of administration for many patients. Greater experience with BiTES has also improved the safety and tolerability of this regimen over time.

This is the second of 2 parts from this event. Read part 1 here.

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Targeted Oncology: What stood out from the subgroups treated in the MajesTEC-3 trial?

Patrick Hagen, MD: [Regarding] the subgroup analysis…there is not much to say here, other than we don’t see any concerning pattern that there’s some specific subgroup that has not been [responding]. The only group that goes over the line is African Americans [HR, 0.19; 95% CI, 0.02-1.49], and they actually do a lot better with a lot of conventional therapy. I think there is nothing to draw from this other than that it is consistent with the main trial findings.¹

There were patients with previous transplant in the trial. I don’t recall the breakdown, but it’s pretty representative of what we would expect. That was not an exclusion criterion; they could have had a transplant.

What was the safety profile seen in this study?

The [rates of] adverse events [AEs] is what I find compelling, because we have changed some of our supportive care with the B-cell maturation antigen BiTEs. We’re much more aggressive, at least in our practice, and most are. If we look at the treatment duration, it is longer in the experimental arms. Patients are staying on therapy. The grade 3 and 4 treatment-related AEs are about the same. I think importantly, although there is a slight increase in infections and grade 3 and 4 infections in the teclistamab/daratumumab arms, there is not a striking difference. That’s always been where our concern is with these therapies.

Cytokine release syndrome is going to be unique to the teclistamab arm, and it’s [primarily] grade 1 and 2, and there’s a low amount of immune effector cell–associated neurotoxicity syndrome in these patients, 1%. I think it is safer than I might have expected. The original BiTE data came out of the COVID-19 [pandemic] era, and there were a lot more infections. We’re also just learning how to get better supportive care with these drugs.

Diving a little bit more into the AEs, in terms of hematological AEs, they were pretty similar between the 2 arms. The hypogammaglobulinemia was [more common] in the teclistamab/daratumumab arm, but not even as much as I would have thought. We see in clinical practice a fair amount grade 3 and 4 hypogammaglobulinemia, but we’re seeing more there; 68% vs 35% any grade, but when we get down to the severe hypogammaglobulinemia, it is about 6% vs only 1.5%, [respectively]. It’s hard to parse out those small numbers, but it’s not as profound as I might expect. Then you look at COVID-19, upper respiratory tract infections, pneumonias, again [there was] a little bit more in the teclistamab/daratumumab arm, but not a dramatic difference. It’s as we would expect, a slight signal for some more infections, but…I would say less than I was expecting.

How common are prolonged cytopenias with teclistamab?

That would be uncommon with the BiTE. We definitely see that with the CAR T-cell therapy, that is certainly a risk. It’s not a common occurrence, but it’s why we’re reaching more and more toward stem cells for those patients. We do very few second transplants anymore, but prolonged cytopenias are when the CAR T cells are a real issue. With a BiTE, it would make me think it’s probably a consequence of recurring infection—marrow suppression from chronic inflammation.

Some of these patients get more infections than you would think. We’re very aggressive with granulocyte colony-stimulating factor and intravenous immunoglobulin in these patients.

Does step-up dosing in a hospital before continuing teclistamab in the community improve access for patients?

Initially, there was some challenges doing step-up dosing in the hospital, because it was a financial loss for the hospital, and we would send patients back to the community right away. That’s not an issue anymore, because we do everything outpatient. I think for patients, there is a relationship with the first oncologist they see that is helpful.

I think the fear over BiTEs has gotten less over time, because I think there’s just more patients getting exposed. It’s more in the myeloma communities, online forums, but there is still a big barrier to CAR T therapy. But I think patients should be getting one of those in the second line now. I think that’s pretty much a slam dunk.

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_{DISCLOSURES: Hagen previously disclosed serving on the speaker’s bureau for Sanofi.}

_REFERENCE

_{1. Costa LJ, Bahlis NJ, Perrot A, et al. Teclistamab plus daratumumab in relapsed or refractory multiple myeloma. N Engl J Med. Published online December 9, 2025. doi:10.1056/NEJMoa2514663}