Dr Kaur on the Potential Effect of CELMoDs on Multiple Myeloma Management

“More than ever, there is a need for novel agents, especially agents that can rescue patients post–CAR T-cell therapy or post–bispecific [antibody progression].”

Gurbakhash Kaur, MD, an assistant professor of medicine, hematology and medical oncology at Mount Sinai, discussed the ongoing investigation of CELMoDs in multiple myeloma, and where these novel agents could fit into the current treatment paradigm.

Kaur explained that the therapeutic landscape within multiple myeloma continues to shift rapidly, with CAR T-cell therapy now approved as early as the second-line setting and other T-cell–directed therapies such as bispecific antibodies being evaluated in earlier lines of therapy. One such regimen is teclistamab-cqyv (Tecvayli) in combination with daratumumab and hyaluronidase-fihj (Darzalex Faspro), which was evaluated in the phase 3 MajesTEC-3 trial (NCT05083169) in patients with relapsed/refractory disease following 1 to 3 prior lines of therapy.

As such, novel treatment approaches for patients who have been exposed to CAR T-cell therapy or bispecific antibodies are needed, Kaur asserted. CELMoDs represent a class of agents that could help address these unmet needs, Kaur stated, adding that CELMoDs could help restore immune fitness in patients who have experienced T-cell exhaustion following prior immune-based therapies. She noted that this concept is clinically relevant as patients transition from one immune therapy to another. The ability of CELMoDs to potentially reinvigorate T-cell function could position them as valuable treatment options both after and between immune-directed approaches.

Early clinical data with next-generation CELMoDs have shown encouraging efficacy in heavily pretreated populations, including patients with prior exposure to multiple drug classes. Preliminary signals of activity in patients with extramedullary disease are particularly noteworthy, given the limited treatment options and poor outcomes typically observed in this subgroup, Kaur explained.

Although the investigation of this class of agents is ongoing, CELMoDs could ultimately be incorporated as post–cellular therapy salvage, bridging therapy prior to CAR T-cell therapy, or possibly in combination regimens earlier in the disease course as data mature, she concluded.