KEY TAKEAWAYS
- The CARTITUDE-4 phase III trial aimed to asses the efficacy and safety of cilta-cel compared to PVd or DPd in lenalidomide-refractory MM patients with 1-3 prior LOT.
- The primary endpoint was PFS.
- The result demonstrated consistent PFS improvements across diverse MM subgroups, including high-risk patients.
Researchers aimed to analyze the safety and efficacy of ciltacabtagene autoleucel(cilta-cel) compared to physician’s choice of standard of care (SOC; pomalidomide, bortezomib, and dexamethasone [PVd] or daratumumab, pomalidomide, and dexamethasone [DPd]) in lenalidomide (len)-refractory multiple myeloma (MM) patients with 1-3 prior lines of therapy(LOT).
Eligible patients, who had received a proteasome inhibitor and an immunomodulatory drug with an Eastern Cooperative Oncology Group (ECOG) status score of ≤1, were randomized. Those assigned to cilta-cel underwent apheresis, received a physician’s chosen bridging treatment (PVd or DPd), and then had one cilta-cel infusion (target dose, 0.75×106 CAR+ viable T cells/kg) 5–7 days after initiating lymphodepletion.
Patients randomized to the SOC group received a physician’s chosen PVd or DPd till disease progression. The primary endpoint was progression-free survival (PFS), and was evaluated using a weighted method focusing on PFS after the period during which both arms were on the same treatment. Subgroup analyses of PFS were reported with HRs and 95% CIs.
About 419 patients were randomized, with a median follow-up of 15.9 months (range: 0.1–27). Among them, 208 were randomized to cilta-cel (of whom 176 received cilta-cel), and 211 to SOC. Baseline characteristics were balanced, with 32.5% having one prior LOT and 6.2% in ISS stage III. High-risk cytogenetics(61.2%) were observed (ie, del(17p), t(14;16), t(4;14) or gain/amp(1q)), with 22.0% having two or more high-risk abnormalities, 18.9% had soft tissue plasmacytomas, 20.5% had bone marrow plasma cells ≥60%, and 15.0% had triple-class refractory disease. Treatment distribution included 12.9% receiving PVd, while 87.1% received DPd.
Cilta-cel demonstrated a significant improvement in PFS across all analyzed subgroups. This included patients aged <65 years (HR 0.24, 95% CI 0.15–0.38) and 65–75 years HR 0.34, (0.19–0.61), those with one prior LOT HR 0.35, (0.19–0.66), ISS stage III HR 0.33, (0.11–0.95), one or more cytogenetic high-risk abnormalities HR 0.25, (0.16–0.38), two or more high-risk abnormalities HR 0.33, (0.17–0.64), soft tissue plasmacytomas HR 0.39, (0.21–0.75), bone marrow plasma cells ≥60% HR 0.28, (0.14–0.59), triple-class refractory disease HR 0.15, (0.05–0.39), as well as in patients treated with PVd HR 0.31, (0.13–0.72) and DPd HR 0.26, (0.18–0.39).
The result demonstrated consistent PFS improvements across diverse MM subgroups, including high-risk patients, mimicking the overall study results and solidifying its efficacy in real-world scenarios.
Source: https://imsannual2023.eventscribe.net/fsPopup.asp?PresentationID=1302387&mode=presInfo
Clinical Trial: https://www.clinicaltrials.gov/study/NCT04181827
Manier S. Additional analysis of CARTITUDE-4: Cilta-cel vs standard of care (PVd or DPd) in lenalidomide-refractory patients with multiple myeloma and 1-3 prior lines of therapy. Presented at: 20th International Myeloma Society Annual Meeting and Exposition.2023.
