A subgroup analysis of the phase 3 CARTITUDE-4 trial reveals that ciltacabtagene autoleucel (cilta-cel; Carvykti) provides significant progression-free survival (PFS) benefits for multiple myeloma patients with poor prognostic features, including high-risk cytogenetics, soft-tissue plasmacytoma, ISS stage III disease, and triple-class exposure. The findings, presented at the 20th International Myeloma Society (IMS) Annual Meeting, underscore the potential of cilta-cel as a valuable treatment option for these challenging patient populations.
High PFS Rates Across High-Risk Subgroups
The study demonstrated that patients with standard (n = 59) or high (n = 105) cytogenetic risk achieved impressive 12-month PFS rates of 89.6% (95% CI, 78.4%-95.2%) and 88.5% (95% CI, 80.7%-93.3%), respectively. Among patients with multiple cytogenetic abnormalities (n = 34), the 12-month PFS rate was 82.4% (95% CI, 64.9%-91.7%). For those with 17p deletions, t(4;14) translocations, or t(14;16) translocations (n = 59), the rate was 86.4% (95% CI, 74.7%-93.0%).
Efficacy in Patients with Soft-Tissue Plasmacytoma and Triple-Class Refractory Disease
Notably, patients with soft-tissue plasmacytoma at baseline (n = 30) exhibited an 86.7% 12-month PFS rate (95% CI, 68.3%-94.8%), compared to 90.3% (95% CI, 84.1%-94.1%) in those without (n = 146). Triple-class refractory patients (n = 20) also showed a high 12-month PFS rate of 90.0% (95% CI, 65.6%-97.4%), versus 89.7% (95% CI, 83.7%-93.5%) in non-refractory patients (n = 156). Patients with prior daratumumab exposure (n = 36) or triple-class exposure (n = 37) experienced 12-month PFS rates of 82.8% (95% CI, 65.7%-91.9%) and 83.3% (95% CI, 66.5%-92.1%), respectively, compared to 84.9% (95% CI, 78.2%-89.7%) in the overall patient population.
Investigator Commentary
"Within the cilta-cel as-treated population, the 12-month PFS rate remained greater than 82% in the presence of common markers of poor prognosis, including high-risk cytogenetics and triple-class refractoriness," said lead study author Salomon Manier, MD, PhD, a professor of medicine at Centre Hospitalier Universitaire de Lille, in Lille, France. "Data in patients with prior daratumumab or triple-class exposure also suggest that cilta-cel is effective when used in this patient population."
Study Design and Patient Population
The CARTITUDE-4 trial enrolled patients with lenalidomide-refractory multiple myeloma who had received 1 to 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent. Patients were randomized to either cilta-cel or physician’s choice of pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd). Patients in the cilta-cel arm received a single infusion of cilta-cel at a target dose of 0.75 × 106 CAR-positive viable T cells/kg following lymphodepletion. The primary endpoint was PFS, with secondary endpoints including complete response rate, overall response rate, minimal residual disease negativity, and overall survival.
Consistent Benefits Across Subgroups
Additional analysis revealed that cilta-cel improved median PFS compared to standard-of-care treatment across all analyzed subgroups, including those with high-risk features. The hazard ratio (HR) for PFS in patients with two or more abnormal markers was 0.33 (95% CI, 0.17-0.64), and in those with del(17p), t(14;16), or t(4;14), it was 0.26 (95% CI, 0.15-0.45). In patients with ISS stage III disease, the HR for PFS was 0.33 (95% CI, 0.11-0.95), and in those with soft-tissue plasmacytomas, it was 0.39 (95% CI, 0.21-0.75). For triple-class refractory patients, the HR for PFS was 0.15 (95% CI, 0.05-0.39), and in those with prior exposure to daratumumab or bortezomib, it was 0.23 (95% CI, 0.12-0.44) and 0.27 (95% CI, 0.19-0.39), respectively.
Clinical Implications
According to Manier, the observed benefits of cilta-cel in patients with poor prognostic features align with the overall ITT population, confirming the effectiveness of a single cilta-cel infusion across a broad spectrum of clinically relevant multiple myeloma subgroups.
