Dr Matous on Barriers to CAR T-Cell Therapy Administration in Multiple Myeloma

Jeffrey V. Matous, MD, member physician, Colorado Blood Cancer Institute, clinical professor of medicine, University of Colorado, discusses potential strategies to overcome barriers to receiving CAR T-cell therapy for patients with multiple myeloma, and how the potential use of these agents in earlier lines could improve infusion wait times and rates of disease progression.

Most patients receiving CAR T-cell therapy will need to wait approximately 5 weeks from the time of apheresis until the infusion of their autologous CAR T cells, Matous begins. During that time, some patients will exhibit aggressive disease that requires bridging therapy to prevent progression, he says. In a clinical trial setting, some of these patients have had to discontinue participation in the study, preventing them from receiving CAR T-cell therapy due to progressive disease, Matous adds.

Accordingly, efforts to decrease the manufacturing time needed for autologous CAR T cells or produce an effective off-the-shelf CAR T-cell therapy remain substantial interests in the field, Matous states, noting that several research groups are pursuing these strategies.

Meanwhile, investigations of both idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel; Carvykti), in earlier lines of therapy could also improve disease control for some patients, Matous continues. Administration of these CAR T-cell therapies in the second or third line could improve patients’ T-cell repertoire, as well as their ability to tolerate these treatments, he explains.

Long-term findings for cilta-cel from the phase 1/2 CARTITUDE-1 trial (NCT03548207) alongside recently presented findings from the phase 3 CARTITUDE-4 trial (NCT04181827) corroborate this prediction, Matous says.

Notably, data from CARTITUDE-4 showed a progression-free survival (PFS) advantage with cilta-cel vs standard-of-care (SOC) pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd) or daratumumab (Darzalex), pomalidomide, and dexamethasone (DPd) in pretreated patients with lenalidomide (Revlimid)-refractory multiple myeloma. This PFS benefit indicated that earlier administration of CAR T-cell therapies such as cilta-cel could improve both outcomes and tolerability with this drug class, Matous concludes.