KEY TAKEAWAYS
- The CARTITUDE-4 phase III trial aimed to compare the efficacy and safety of cilta-cel to the standard of care in lenalidomide-refractory multiple myeloma patients.
- The primary endpoint was to determine PFS in the population intended to be treated randomized.
- The study demonstrated superior PFS and safety compared to standard of care in lenalidomide-refractory multiple myeloma pts, establishing its potential as a transformative treatment option.
Researchers aimed to compare the efficacy and safety of cilta-cel, a CAR-T cell therapy, to standard-of-care treatments in patients with multiple myeloma who had failed to respond to lenalidomide.
Patients eligible for the study had 1–3 prior lines of therapy (LOT), including proteasome inhibitors (PI) and immunomodulatory drugs, and were refractory to lenalidomide. Following apheresis, those randomized to cilta-cel underwent bridging therapy with PVd or DPd (physician’s choice), followed by a single cilta-cel infusion (target dose 0.75×106 CAR+ viable T cells/kg) 5–7 days after lymphodepletion.
Patients in the standard of care (SOC) group received PVd or DPd (physician’s choice) until disease progression. The primary endpoint, progression-free survival (PFS), was analyzed in the intent-to-treat (randomized) population. Informed consent was obtained before study entry.
About 419 patients were randomized(cilta-cel, n=208; SOC, n=211 [PVd, n=28; DPd, n=183]. Planned cilta-cel treatment was administered to 176 patients, while 20 more received cilta-cel after progressive disease (PD) during bridging therapy, and 208 received SOC treatment. There were no manufacturing failures, and baseline characteristics were balanced between cilta-cel and SOC groups(cilta-cel vs SOC: 59% vs 63% cytogenetic high risk [including gain/amp 1q]; 50% vs 46% PI refractory; 24% vs 22%anti-CD38 refractory; 33% vs 32% had 1 prior LOT).
The median dose of cilta-cel was 0.71×106 CAR+ viable T cells/kg. As of the November 1, 2022, data cutoff, with a median follow-up of 16 months (range, 0.1–27), the primary endpoint was achieved; cilta-cel reduced the risk of progression/death by 74% (HR=0.26; P-value [P] <0.0001). In the cilta-cel group, patients demonstrated significantly improved overall response rate, complete response (CR) or better rate, and overall minimal residual disease (MRD) negativity rate compared to the standard of care (SOC) group (see Table), with a positive trend in overall survival (HR, 0.78; 95% CI, 0.5–1.2).
Grade 3/4 adverse events were observed in 97% and 94% of patients in the cilta-cel and SOC groups, respectively, including infections (27% vs 25%) and cytopenias (94% vs 86%). In the cilta-cel and SOC groups, 39 and 46 patients died, respectively (14 and 30 due to progressive disease [PD]).
Among patients who received cilta-cel as study treatment (n=176), 76% experienced cytokine release syndrome (1% grade 3; no grade 4/5), and 5% had immune effector cell-associated neurotoxicity syndrome (all grade 1/2). A single case of movement and neurocognitive treatment-emergent adverse event was reported (grade 1).
The study demonstrated superior PFS and safety compared to standard of care in lenalidomide-refractory multiple myeloma pts, establishing its potential as a transformative treatment option.
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04181827
Einsele, H. (2023). FIRST PHASE 3 RESULTS FROM CARTITUDE-4: CILTA-CEL VERSUS STANDARD OF CARE (PVD OR DPD) IN LENALIDOMIDE-REFRACTORY MULTIPLE MYELOMA. Abstract presented at EHA 2023.
