Dr Dhakal on the Design of the CARTITUDE-4 Study in R/R Myeloma

Binod Dhakal, MD, associate professor, Division of Hematology and Oncology, Medical College of Wisconsin, discusses the design of the phase 3 CARTITUDE-4 study (NCT04181827) of ciltacabtagene autoleucel (Carvykti; cilta-cel) in patients with relapsed/refractory multiple myeloma and highlights next steps for researching this agent.

Notably, Dhakal and colleagues shared updated survival resultsfrom the study at the 21st International Myeloma SocietyAnnual Meeting. At a median follow-up of 33.6 months (range, 0.1-45.0), the 30-month overall survival (OS) rate for patients treated with cilta-cel was 76.4% compared with 63.8% for patients receiving standard-of-care (SOC) treatment (HR, 0.55; 95% CI, 0.39-0.79; P = .0009). This corresponds to a 45% reduction in the risk of death.

The phase 3 randomized trial compares cilta-cel with SOC in patients who had received 1 to 3 prior lines of therapy, including those refractory to lenalidomide (Revlimid), Dhakal begins. Patients were randomly assigned 1:1 to either the cilta-cel arm or the SOC arm. The SOC consisted of 1 of 2 regimens: pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd), or daratumumab (Darzalex) plus pomalidomide and dexamethasone (DPd); both were considered effective standard regimens at the time of the investigation, he reports. Patients who received cilta-cel underwent bridging therapy with either PVd or DPd based on physician choice, followed by a single infusion of cilta-cel, and then entered a follow-up phase.

The primary end point of the study is progression-free survival (PFS), and secondary end points include OS, response rates, minimal residual disease negativity, quality of life, and safety assessments, he expands. Dhakal says investigators continue to monitor patients for long-term safety and to identify emerging safety signals. Notably, the median PFS has not yet been reached, which remains a key focus as the trial progresses, he notes.

The phase 3 CARTITUDE-5 (NCT04923893) and CARTITUDE-6 (NCT05257083) trials are underway to evaluate the use of cilta-cel in newly diagnosed multiple myeloma, Dhakal continues. CARTITUDE-5 is enrolling patients who are not eligible for or have deferred transplant, and CARTITUDE-6 is enrolling transplant-eligible patients, comparing CAR T-cell therapy with stem cell transplant, he states. These trials will provide valuable insights into the role of CAR T-cell therapy in the frontline treatment of multiple myeloma, Dhakal concludes.