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

• Published in: HemaSphere 2019-06, Vol.3 (S1), p.797-n/a
• Main 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.
• Format: Article
• Language: English
• ISSN: 2572-9241; 2572-9241
• DOI: 10.1097/01.HS9.0000565440.29342.2a

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 (40%–60%, or >60%); of note, patients may have had a baseline bone marrow blast percentage 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+