Dr Mikhael on Research Developments in Multiple Myeloma

Joseph Mikhael, MD, professor, Applied Cancer Research and Drug Discovery Division, Translational Genomics Research Institute, City of Hope, chief medical officer, International Myeloma Foundation, discusses treatment advancements and ongoing research for patients with multiple myeloma.

The 2023 ASH Annual Meeting featured an extensive array of research in multiple myeloma, indicating the increasing significance of myeloma as a rapidly growing area of focus within ASH, Mikhael says. Topics ranged from research in smoldering myeloma, to frontline therapy for active myeloma, as well as treatment strategies for early and late relapsed disease, Mikhael explains. Other abstracts focused on future treatment regimens under investigation in phase 1 trials, Mikhael added.

Both a plenary session and a late-breaking abstract session at the meeting highlighted the superiority of quadruplet regimens over triplet regimens in the frontline setting, Mikhael emphasizes. Studies showed that combining an anti-CD38 antibody with a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and dexamethasone was superior to using an anti-CD38 antibody, PI, and IMiD alone in in transplant-eligible patients. This showcases the efficacy of first-line regimens such as daratumumab (Darzalex) plus carfilzomib, lenalidomide, and dexamethasone (KRd) and isatuximab-irfc (Sarclisa) plus KRd, according to Mikhael.

Additional research is ongoing in transplant-ineligible patient populations, including the phase 3 IMROZ trial (NCT03319667). This trial is comparing isatuximab plus bortezomib, lenalidomide, and dexamethasone (VRd) vs VRd alone, Mikhael says. Overall, approaches to myeloma management in the front line have shifted in favor of quadruplet regimens for most patients, as these therapies may achieve deeper and more durable responses than triplet combinations, Mikhael notes.

Research is also underway to enhance the efficacy of CAR T-cell therapy and explore new targets and combinations for bispecific antibodies in multiple myeloma, Mikhael says. The goal is to make these agents more tolerable and accessible for patients. For example, weekly administration of bispecific antibodies could be adjusted to a more manageable dosing schedule, Mikhael states. Overall, it is encouraging to see impactful research being conducted in both the frontline and relapsed settings in multiple myeloma, Mikhael concludes.