Dr. Chari on Avenues for Future Research in Newly Diagnosed Multiple Myeloma

Ajay Chari, MD, professor of medicine, director of Clinical Research, Multiple Myeloma Program, Icahn School of Medicine at Mount Sinai, discusses several avenues for future study in newly diagnosed multiple myeloma.

Research focused on transplant-ineligible patients shows that the dosage and scheduled administration of available therapeutics may be more important in achieving good responses than the number of agents included in a treatment combination, Chari begins. This is supported by data from the phase 3 MAIA trial (NCT02252172) of daratumumab (Darzalex) plus lenalidomide (Revlimid) and dexamethasone (D-Rd) vs lenalidomide and dexamethasone (Rd). Although the addition of daratumumab to Rd did cause a small increase in neutropenia, it extended progression-free survival and improved overall survival. Subsequent subgroup analysis showed deep and durable responses in this patient population. Therefore, the increase in toxicity does not negate the benefit seen with this combination, Chari explains.

Other efforts aim to identify a potential role for the proteasome inhibitor bortezomib (Velcade) in the treatment of patients with newly diagnosed multiple myeloma, Chari continues. For example, a phase 2 trial (NCT04052880) at Mount Sinai is investigating a regimen of daratumumab plus bortezomib, lenalidomide and dexamethasone (VRd) lite in elderly, high-risk patients with extramedullary disease.

Conversely, research efforts in transplant-eligible populations should focus on evaluating quadruplet combinations with and without autologous transplant, and the use of CAR T-cell therapies as a potential substitute for transplant, Chari says. Data on successful displacement of transplant with CAR T-cell therapies has yet to be seen, but researchers hypothesize that CAR T cells may consolidate the antigenic release seen after a melphalan administration, he notes. Lastly, maintenance regimens require improvement for this population. Previous data indicate that doublet maintenance with carfilzomib (Kyprolis) may help prevent relapse, but its prolonged use comes with several practical challenges that must be addressed, Chari concludes.