Survival outcomes with CPX-351 vs 7+3 by baseline bone marrow blast percentage in older adults with newly diagnosed high-risk or secondary acute myeloid leukemia: A 5-year follow-up study.

Background: CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, is approved for newly diagnosed therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes in the US and Europe following positive efficacy and safety data from the pivotal phase 3 clinical trial (NCT01696084). A previous exploratory analysis of the trial data (median follow-up 20.7 months) showed improved survival outcomes with CPX-351 vs conventional 7 + 3 chemotherapy in adults with newly diagnosed high-risk or secondary AML (sAML) irrespective of baseline bone marrow (BM) blast percentage1. Aims: Here, we report 5-year follow-up data (median follow-up 60.9 months) to provide insights into the longer-term efficacy of CPX-351, considering patient baseline BM blast percentage. Methods: Patients (60–75 years) with a pathologic diagnosis of AML (high-risk/sAML) per the WHO 2008 criteria (≥20% blasts in peripheral blood or BM) and an ECOG PS of 0–2 were randomized to receive CPX-351 or 7 + 3 chemotherapy. In these post hoc subgroup analyses at 5-year follow-up, overall survival (OS), event-free survival (EFS) and complete remission (CR) were assessed by subgrouping patients into four categories based on baseline BM blast percentage: <20%, 20–40%, >40–60% and >60%. The analysis included patients with low (<20%) BM blasts to account for changes in blast count thresholds in the updated WHO AML classification. Patients may have had a baseline BM blast percentage <20% with an AML diagnosis based on ≥20% blasts in peripheral blood and/or confirmation by an independent pathologist based on other factors. Results: Overall, median OS and EFS were longer with CPX-351 vs 7 + 3 in each subgroup (Table). However, median OS was greatest in the <20% baseline BM blast subgroup for both treatments (12.6 months for CPX-351 vs 7.3 months for 7 + 3) and lowest in the >60% baseline BM blast subgroup (4.7 months for CPX-351 vs 2.9 months for 7 + 3). Additionally, Median Kaplan-Meier (KM)–estimated survival rates increased with CPX-351 vs 7 + 3 across BM blast subgroups. Higher CR rates were observed with CPX-351 vs 7 + 3 irrespective of baseline BM blasts, with the greatest difference between treatment groups seen in the >40–60% baseline BM blast subgroup (47% vs 24%, respectively). The CPX-351 safety profile was comparable across BM blast subgroups and consistent both with previous reports and the known safety profile of 7 + 3. Summary/Conclusion: These 5-year follow-up data suggest that CPX-351 results in improved outcomes irrespective of baseline BM blast percentage vs conventional 7 + 3 chemotherapy in older adults with AML. Table. Efficacy outcomes with CPX-351 vs 7 + 3 chemotherapy, stratified by baseline BM blast percentage - Baseline BM blasts <20%a 20%–40% >40%–60% >60% Treatment CPX-351 7 + 3 CPX-351 7 + 3 CPX-351 7 + 3 CPX-351 7 + 3 n 21 22 62 65 34 34 32 29 Median OS, mo 12.6 7.3 11.6 6.0 8.1 4.9 4.7 2.9 HR (95% CI) 0.38 (0.19, 0.75) 0.62 (0.42, 0.91) 0.72 (0.43, 1.21) 0.67 (0.40, 1.14) Median KM–estimated 5-year survival rate % (95% CI) 26.0 (9.6, 46.1) 0 22.4 (12.9, 33.4) 9.2 (3.8, 17.7) 19.4 (8.1, 34.4) 8.8 (2.3, 21.1) 6.3 (1.1, 18.1) 3.4 (0.30, 14.9) Median EFS, mo 3.0 1.1 2.5 2.2 5.0 1.0 2.0 1.2 HR (95% CI) 0.60 (0.32, 1.14) 0.81 (0.55, 1.18) 0.45 (0.27, 0.77) 0.54 (0.31, 0.95) CR, n (%) 7 (33) 5 (23) 25 (40) 21 (32) 16 (47) 8 (24) 9 (28) 4 (14) OR (95% CI) 3.78 (0.68, 21.05) 1.22 (0.56, 2.66) 2.89 (0.99, 8.44) 1.72 (0.41, 7.21) aPatients may have had a baseline BM blast percentage <20% with an AML diagnosis based on ≥20% blasts in peripheral blood and/or confirmation by an independent pathologist. References: 1. Ritchie EK, et al. Journal of Clinical Oncology 2019 37:15_suppl, 7042-7042. Keywords: Long-term follow-up, Chemotherapy, Survival, Acute myeloid leukemia