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.

Ellen K. Ritchie Weill Cornell Medicine, The New York Presbyterian Hospital, New York, NY info_outline Ellen K. Ritchie, Tara L. Lin, Laura F. Newell, Robert K. Stuart, Scott R. Solomon, Richard M. Stone, Gary J. Schiller, Matthew Joseph Wieduwilt, Eileen A. Ryan, Nalina Dronamraju, Jeffrey E. Lancet, Jorge E. Cortes

Authors Ellen K. Ritchie Weill Cornell Medicine, The New York Presbyterian Hospital, New York, NY info_outline Ellen K. Ritchie, Tara L. Lin, Laura F. Newell, Robert K. Stuart, Scott R. Solomon, Richard M. Stone, Gary J. Schiller, Matthew Joseph Wieduwilt, Eileen A. Ryan, Nalina Dronamraju, Jeffrey E. Lancet, Jorge E. Cortes Organizations Weill Cornell Medicine, The New York Presbyterian Hospital, New York, NY, University of Kansas Medical Center, Kansas City, KS, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, Northside Hospital Cancer Institute, Atlanta, GA, Dana-Farber Cancer Institute, Boston, MA, David Geffen School of Medicine at UCLA, Los Angeles, CA, Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC, University of Rochester, Rochester, NY, Jazz Pharmaceuticals, Philadelphia, PA, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, Georgia Cancer Center, Augusta, GA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Celator Pharmaceuticals, Inc., now a subsidiary of Jazz Pharmaceuticals 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 percentage. Here we report 5-year follow-up data (median follow-up 60.9 months) to provide insights into the longer-term efficacy and safety of CPX-351 in these patient subgroups. 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 years follow-up, overall survival (OS), event-free survival (EFS) and complete remission (CR) were assessed by baseline BM blast percentage. The analysis included patients with low ( < 20%) BM blasts to account for changes in blast count thresholds in the updated WHO AML classification. Results: Overall, median OS and EFS were longer with CPX-351 vs 7+3 in each subgroup; median OS was greatest in low blast subgroups for both treatments (Table). Higher CR rates were observed with CPX-351 vs 7+3 irrespective of baseline BM blasts. Median Kaplan-Meier (KM)-estimated survival rates increased with CPX-351 vs 7+3 across BM blast subgroups. The CPX-351 safety profile was comparable across BM blast subgroups and consistent with the known safety profile of 7+3. Conclusions: 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. Clinical trial information: NCT01696084. 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 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) 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) a AML diagnosis confirmed by an independent pathologist; patients may have had baseline BM blasts < 20% with AML diagnosis based on other factors.

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