Dr Sasine on the Potential Use of Cilta-Cel in Earlier Lines for Multiple Myeloma

Joshua P. Sasine, MD, PhD, hematologist/oncologist, assistant professor, Cedars-Sinai Medical Center, discusses the potential role of ciltacabtagene autoleucel (cilta-cel; Carvykti) in earlier lines of therapy for patients with multiple myeloma.

The phase 3 CARTITUDE-4 trial (NCT04181827) evaluated the use of cilta-cel vs standard-of-care (SOC) pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd) or daratumumab (Darzalex), pomalidomide, and dexamethasone (DPd) in patients with lenalidomide (Revlimid)-refractory multiple myeloma who had previously received 1 to 3 prior lines of therapy. In the trial, cilta-cel provided a significant progression-free survival advantage to patients across all prespecified groups vs SOC regimens. Overall, results from the trial indicated that cilta-cel in earlier lines could not only improve tolerability but could become new standard of care for patients with lenalidomide-refractory myeloma.

Based on this trial, cilta-cel continues to be the focus on ongoing efforts to move CAR T-cell therapy into earlier lines in myeloma. Several ongoing trials are also comparing the agent's efficacy with that of autologous stem cell transplant (ASCT) in this disease space, Sasine remarks. Previously reported data has shown that ASCT also provides a substantial, consistent PFS benefit for patients with multiple myeloma. However, it is historically difficult to demonstrate an overall survival (OS) advantage with ASCT in this setting, and research on cilta-cel may encounter a similar problem, Sasine states. Additionally, OS results may lead to discussion regarding whether the lack of a true crossover trial design influenced results, he notes.

With potential uncertainty surrounding OS results, PFS and toxicity profiles will be the most important measures to consider when determining if cilta-cel should be used in earlier lines, and if it should be used before ASCT, Sasine asserts. Patients who are elderly or have high-risk disease may benefit from earlier utilization of CAR T-cell therapy due to its superior tolerability vs ASCT, he says. However, more data are needed to determine if this approach should consistently replace ASCT in the frontline for standard-risk patients, Sasine concludes.