Ajay K. Nooka, MD, MPH, on MajesTEC-3 Data, Dropping Dexamethasone in MM

Ajay K. Nooka, MD, MPH, an investigator in the MajesTEC-3 trial (NCT05083169), discussed how the multiple myeloma (MM) treatment landscape is shifting in 2026. Nooka is also a professor in the Department of Hematology and Medical Oncology, director of the Myeloma Program, and associate director of clinical research at the Winship Cancer Institute, Emory University School of Medicine.

In his view, every new patient in the US, transplant-eligible or not, should now be receiving quadruplet regimens, noting that roughly 70% of real-world patients already do, with that number expected to climb further. He emphasized that dose-reduced quadruplets consistently outperform full-dose triplets in achieving deep responses.

A key caveat, he noted, is that most US patients have already been exposed to CD38-targeted antibodies, a population underrepresented in MajesTEC-3, where only 5% of participants had prior CD38 exposure. This raises open questions about how applicable the trial’s results are to real-world US patients. Still, Nooka argued that prior daratumumab (dara) exposure should not necessarily preclude its later use, distinguishing exposure from true refractoriness, although he acknowledged uncertainty remains for patients who are dara-refractory receiving daratumumab alongside teclistamab.

Turning to regulatory strategy, Nooka explained that MajesTEC-3’s approval of teclistamab was driven by a clear progression-free survival (PFS) benefit rather than surrogate end points. He suggested that as control arms in myeloma trials grow stronger, future studies may take years longer to read out, making early end points like minimal residual disease (MRD) negativity valuable as co-primary measures—allowing earlier approvals while still requiring confirmatory PFS data.

Lastly, Nooka addressed dexamethasone (dex), calling it among the most poorly tolerated drugs in myeloma care despite its long-standing routine use.

“When you start to look at what’s the drug that is most hated by the patients, what’s the drug that is most hated by the physicians, what’s the drug that has the most number of side effects, what’s the drug that is called the worst pill, this all happens to be one drug, which is dexamethasone,” he said.

Nooka noted that bispecific antibody regimens are increasingly demonstrating strong efficacy without relying on dex as an active agent, using it only as a premedication. He expressed hope that MajesTEC-3 may represent an early step toward eliminating dexamethasone from myeloma regimens altogether, given its strong PFS, overall survival, response rate, and MRD negativity outcomes.