Ciltacabtagene autoleucel in lenalidomide-refractory multiple myeloma responding to bridging therapy: CARTITUDE-4 cytogenetic subgroup analysis.

Abstract

7536 Background: CARTITUDE-4 (NCT04181827) showed significant overall (OS) and progression-free survival (PFS) benefits of ciltacabtagene autoleucel (cilta-cel) in patients with lenalidomide-refractory multiple myeloma (MM) after 1–3 lines of therapy. Emerging data underscore the importance of successful bridging therapy (BT); deeper responses (partial response or better, ≥PR) during BT were associated with better survival and safety outcomes in patients treated with cilta-cel. Here, we present efficacy and safety in patients who received cilta-cel as study treatment with high- and standard-risk cytogenetics who responded to BT. Methods: CARTITUDE-4 as-treated set comprised patients who received a single cilta-cel infusion as study treatment after apheresis, ≥1 BT cycle, and lymphodepletion. High-risk cytogenetics were defined as positivity for del(17)p, t(14;16), t(4;14) or gain/amp(1q); standard-risk patients were negative for these mutations. Responses to BT were assessed based on International Myeloma Working Group criteria. Efficacy and safety from as-treated patients with ≥PR to BT were analyzed in high- and standard-risk cytogenetics subgroups. Results: Of 176 patients who received cilta-cel as study treatment (median follow-up, 33.6 months), 64 patients had high-risk cytogenetics and achieved ≥PR to BT. In these patients, median PFS and OS were not reached; 30-month PFS and OS rates were 65.1% (95% CI, 51.4–75.8) and 87.2% (95% CI, 76.1–93.4), respectively. In 40 patients with standard-risk cytogenetics and ≥PR to BT, median PFS and OS were not reached; 30-month PFS and OS rates were 85.0% (95% CI, 69.6–93.0) and 92.5% (95% CI, 78.5–97.5), respectively. Safety analysis included 64 patients with high-risk and 40 with standard-risk cytogenetics. In the high-risk subgroup, cytokine release syndrome was reported in 73.4% of patients, serious nonhematological adverse events in 64.1%, grade 3/4 infections in 43.8%, and immune effector cell-associated neurotoxicity syndrome in 7.8%. Corresponding rates in the standard-risk subgroup were 70.0%, 57.5%, 30.0%, and 0. Nonrelapse mortality (NRM) occurred in 9 patients (high-risk, 7; standard-risk, 2); there were 4 infection-related deaths in the high-risk population. No cases of immune effector cell (IEC)-parkinsonism were reported in high- and standard-risk subgroups. Conclusions: This analysis showed survival and response benefits of cilta-cel in patients with high- and standard-risk cytogenetics who had achieved ≥PR to BT, with >85% of patients alive at 30 months. No patients had IEC-parkinsonism, and infections were a key cause of NRM. These data highlight the profound benefit that cilta-cel can provide to patients with high- and standard-risk cytogenetics when MM is well controlled at time of infusion. Clinical trial information: NCT04181827 .