Background on the CARTITUDE-4 Trial of Cilta-Cel in Multiple Myeloma

Binod Dhakal, MD, MS, assistant professor of medicine in the Division of Hematology and Oncology at the Medical College of Wisconsin, provides background on the phase 3 CARTITUDE-4 study (NCT04181827) of ciltacabtagene autoleucel (cilta-cel; Carvykti) for the treatment of patients with lenalidomide-refractory multiple myeloma.

CARTITUDE-4 study is a global, randomized, controlled, phase 3 study evaluating the dual-binding, BCMA-targeting chimeric antigen receptor (CAR) T-cell therapy, cilta-cel, compared with the standard-of-care (SOC) regimen of pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd) or daratumumab (Darzalex), pomalidomide, and dexamethasone (DPd) in lenalidomide-refractory patients with multiple myeloma.

A total of 419 patients were enrolled and randomized in the study, including 208 patients who were treated with cilta-cel and 211 who received SOC. Baseline characteristics were balanced between treatment arms. In the cilta-cel group, 59% of patients vs 63% in the SOC group were cytogenetic high-risk, 24% vs 22% were anti-CD38 refractory, and 33% vs 32% had 1 prior line of therapy.

The primary end point being evaluated in the study is progression-free survival (PFS) , and secondary end points include complete response (CR) or stringent CR rate, overall minimal residual disease (MRD) negativity rate, sustained MRD negativity rate, overall survival, overall response rate, time to worsening of symptoms, PFS on next-line therapy, incidence and severity of adverse events, systemic cytokine concentrations, levels of CAR-T cell activation markers, levels of JNJ-68284528 T-cell expansion and persistence, number of patients with anti-JNJ-68284528 antibodies, and change from baseline in health-related quality of life.

Transcription:

0:10 | CARTITUDE-4 is a phase 3 randomized study evaluating cilta-cel, which is a BCMA-directed CAR T-cell therapy vs standard-of-care regimens in patients with lenalidomide-refractory multiple myeloma after 1,2, or 3 prior lines of therapy.

0:27 | Cilta-cel is a dual binding BCMA-directed CAR T-cell therapy. It is an autologous CAR T product that means the patient's provide T cells which are manufactured to become CAR T cells. Cilta-cel has been studied in patients with 3 or more prior lines of therapy and [other] data has shown that cilta-cel is highly effective and the median PFS is almost 3 years in patients with a heavily refractory disease. CARTITUDE-4 is for patients with 1,2, or 3 prior lines of therapy and a little bit less heavily treated, but it's the first randomized study to include patients after the first relapse.