Cilta-cel Meets PFS End Point in Relapsed/Lenalidomide-Refractory Multiple Myeloma

Ciltacabtagene autoleucel (cilta-cel; Carvykti) demonstrated a significant improvement in progression-free survival (PFS) in patients with relapsed/lenalidomide (Revlimid)-refractory multiple myeloma who received 1 to 3 prior lines of therapy, meeting the primary end point of the phase 3 CARTITUDE-4 trial (NCT04181827).¹

After CARTITUDE-4 met its PFS end point at the first prespecified interim analysis, the study’s independent data monitoring committee recommended unblinding the trial. Full results will be presented at an upcoming scientific congress and shared with health authorities in planned submission applications.

“The CARTITUDE-4 study represents the first phase 3 program in our comprehensive clinical development strategy for [cilta-cel] and further demonstrates our commitment to advance the treatment of patients with relapsed/refractory multiple myeloma,” Jordan Schecter, MD, vice president of the Clinical Development Cellular Therapy Program at Janssen Research & Development, stated in a news release. “We look forward to the presentation of the data from the CARTITUDE-4 study at a future medical meeting.”

In February 2021, the FDA approved cilta-cel for the treatment of adult patients with relapsed/refractory multiple myeloma following 4 or more prior lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody, based on findings from the phase 1b/2 CARTITUDE-1 trial (NCT03548207).²

CARTITUDE-4 evaluates the safety and efficacy of cilta-cel, a BCMA-targeted CAR T-cell therapy. The study enrolled patients with relapsed/refractory multiple myeloma who received 1 to 3 prior lines of therapy, including a PI and an IMiD. Patients needed to have documented evidence of disease progression within 6 months of their last regimen and were required to be refractory to lenalidomide with failure to achieve minimal response or progression on or within 60 days of completing lenalidomide therapy.³

Key exclusion criteria included prior treatment with any CAR T-cell therapy, any prior BCMA-targeted therapy, and treatment with a monoclonal antibody within 21 days, cytotoxic therapy with 14 days, proteasome inhibitor therapy within 14 days, and immunomodulatory drug therapy with 7 days of study treatment.

Enrolled patients were randomly assigned to cilta-cel, pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd); or daratumumab (Darzalex), pomalidomide, and dexamethasone (DPd). Those in the cilta-cel arm received at least 1 cycle of bridging therapy with PVd or DPd, and additional cycles were allowed based on a patient’s clinical status and the timing of cilta-cel treatment. Patients received consolidation therapy with 300 mg/m² of cyclophosphamide and 30 mg/m² of fludarabine for 3 days prior to being administered cilta-cel at a target dose of 0.75 x 10⁶ CAR+ T cells/kg.

Those in the comparator arm were administered PVd consisting of 4 mg of oral pomalidomide on days 1 and 14 in each 21-day cycle, 1.3 mg/m² of subcutaneous bortezomib on days 1, 4, 8, and 11 of cycles 1 to 8 and days 1 and 8 of each cycle thereafter, and 20 mg of oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11 and 12 of cycles 1 to 8, followed by days 1, 2, 8, and 9 in cycle 9 and beyond. Those treated with DPd were treated on 28-day cycles, where they received 1800 mg of subcutaneous daratumumab weekly on days 1, 8, 15, and 22 in cycles 1 and 2, every 2 weeks on days 1 and 15 in cycles 3 to 6, and every 4 weeks on day 1 in cycle 7 and beyond, 4 mg of oral pomalidomide 4 mg on days 1 to 21 of each cycle, and 40 mg of oral or intravenous dexamethasone weekly on days 1, 8, 15, and 22 of each cycle.

Along with the primary end point of PFS, key secondary end points included safety, overall survival, rate of minimal residual disease negativity, and overall response rate. Patients will continue to be followed for primary, secondary, and exploratory end points.

References

• Janssen announces unblinding of phase 3 CARTITUDE-4 study of Carvykti^® (cilta-cel) as primary endpoint met in treatment of patients with relapsed and refractory multiple myeloma. News release. Janssen. January 27, 2023. Accessed January 27, 2023. http://bit.ly/409OA00
• U.S. FDA approves Carvykti™ (ciltacabtagene autoleucel), Janssen’s first cell therapy, a BCMA-directed CAR-T immunotherapy for the treatment of patients with relapsed or refractory multiple myeloma. News release. Janssen. February 28, 2022. Accessed January 27, 2023. https://bit.ly/35yWwjv
• A study comparing JNJ-68284528, a CAR-T therapy directed against B-cell maturation antigen (BCMA), versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in participants with relapsed and lenalidomide-refractory multiple myeloma (CARTITUDE-4). ClinicalTrials.gov. Updated January 28, 2023. Accessed January 27, 2023. https://clinicaltrials.gov/ct2/show/NCT04181827