PB1733 OUTCOMES WITH CPX‐351 VERSUS 7+3 BY BASELINE BONE MARROW BLAST PERCENTAGE IN OLDER ADULTS WITH NEWLY DIAGNOSED, HIGH‐RISK/SECONDARY AML: EXPLORATORY ANALYSIS OF A PHASE 3 STUDY
Authors: Ritchie E.K. , Lin T.L. , Stuart R.K. , Solomon S.R. , Schiller G.J. , Wieduwilt M.J. , Ryan D.H. , Ryan R.J. , Chiarella M. , Cortes J.E. 
Published: June 2019

Background:CPX‐351 (Vyxeos®; daunorubicin and cytarabine powder for concentrate for solution for infusion), a dual‐drug liposomal encapsulation of cytarabine and daunorubicin at a synergistic ratio, is approved by the EMA and the US FDA for the treatment of adults with newly diagnosed, therapy‐related AML or AML with myelodysplasia‐related changes. In a randomized phase 3 study, induction followed by consolidation with CPX‐351 significantly improved median overall survival (OS) versus conventional 7+3 cytarabine/daunorubicin chemotherapy (9.56 vs 5.95 months; HR = 0.69 [95% CI: 0.52‐0.90; 1‐sided P = 0.003) and had a safety profile comparable to 7+3 in adults aged 60‐75 years with newly diagnosed, high‐risk/secondary AML (Lancet, et al. J Clin Oncol 2018). Some studies suggest a high baseline blast percentage may portend a worse prognosis in AML (DiNardo, et al. Am J Hematol 2016; Hasserjian, et al. Am J Hematol 2014).Aims:This exploratory analysis of the phase 3 study assessed outcomes by baseline bone marrow blast percentage.Methods:A total of 309 patients with AML confirmed by an independent pathologist (per 2008 WHO criteria: ≥20% blasts in either peripheral blood or bone marrow) were randomized 1:1 to receive up to 2 induction cycles of CPX‐351 (100 units/m2 [daunorubicin 44 mg/m2 + cytarabine 100 mg/m2] on Days 1, 3, and 5 [2nd induction: Days 1 and 3]) or 7+3 (cytarabine 100 mg/m2/day continuously for 7 days [2nd induction: 5 days] + daunorubicin 60 mg/m2 on Days 1‐3 [2nd induction: Days 1‐2]). Patients achieving complete remission (CR) or CR with incomplete platelet or neutrophil recovery (CRi) could receive up to 2 consolidation cycles with CPX‐351 (65 units/m2 [daunorubicin 29 mg/m2 + cytarabine 65 mg/m2] on Days 1 and 3) or 5+2 (as for 2nd induction). In this exploratory analysis, outcomes were compared among subgroups of patients categorized by baseline bone marrow blast percentage (<20%, 20%–40%, >40%–60%, or >60%); of note, patients may have had a baseline bone marrow blast percentage <20% with diagnosis of AML confirmed based on other factors.Results:Patients treated with CPX‐351 versus 7+3 had longer median OS across baseline bone marrow blast groups, including patients with <20% blasts (12.62 vs 7.31 months), 20%–40% blasts (11.56 vs 5.95 months), >40%–60% blasts (8.77 vs 4.86 months), or >60% blasts (4.65 vs 2.92 months; Table 1). Patients treated with CPX‐351 also had longer event‐free survival (EFS) and higher rates of CR and CR+CRi than those treated with 7+3, irrespective of baseline bone marrow blast percentage (Table 1). Of note, outcomes were generally worse among patients with higher baseline bone marrow blast percentages for both the CPX‐351 and 7+3 treatment arms. The incidence of grade ≥3 treatment‐emergent adverse events (TEAEs) was >80% for both arms; the most frequently reported grade ≥3 TEAEs in both treatment arms were febrile neutropenia, pneumonia, and hypoxia (Table 2). Few TEAEs leading to discontinuation were reported with CPX‐351 or 7+3 (≤5%). The frequency of TEAEs leading to death increased with baseline bone marrow blast percentage, especially for the 7+3 arm.Summary/Conclusion:Improved survival and remission rates were observed with CPX‐351 versus 7+3 irrespective of baseline bone marrow blast percentage in older adults with newly diagnosed high‐risk/secondary AML.image