Outcomes in Patients with Acute Myeloid Leukemia with Myelodysplasia-Related Changes (AML-MRC) Who Achieved Remission with CPX-351 Versus 7+3: Phase 3 Exploratory Analysis

Introduction The WHO 2016 AML-MRC designation applies to AML patients (pts) with a history of myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm, a MDS-related cytogenetic abnormality, or multilineage dysplasia in >50% of ≥2 cell lineages in the absence of NPM1 or biallelic CEBPA mutations. AML-MRC pts typically have a poor prognosis after induction chemotherapy. CPX-351 (Vyxeos®; daunorubicin and cytarabine liposome for injection), a dual-drug liposomal encapsulation of cytarabine [C] and daunorubicin [D] at a synergistic ratio, is approved by the FDA and EMA for the treatment of adults with newly diagnosed therapy-related AML or AML-MRC. A phase 3 study (NCT01696084) in older pts (60-75 y) with newly diagnosed high-risk/secondary AML found that CPX-351 significantly improved median overall survival (OS) vs conventional 7+3, with a comparable safety profile. Objectives An exploratory subgroup analysis of the phase 3 study compared outcomes in pts with AML-MRC who achieved complete remission (CR) or CR with incomplete neutrophil or platelet recovery (CRi). Methods Pts were randomized 1:1 to receive 1-2 induction cycles with CPX-351 (100 units/m2 [C 100 mg/m2 + D 44 mg/m2] as a 90-min infusion on Days 1, 3, and 5 [2nd induction: Days 1 and 3]) or 7+3 (C 100 mg/m2/d continuously for 7 d [2nd induction: 5 d] + D 60 mg/m2 on Days 1-3 [2nd induction: Days 1-2]). Pts achieving CR or CRi could receive up to 2 consolidation cycles with CPX-351 (65 units/m2 [C 65 mg/m2 + D 29 mg/m2] on Days 1 and 3) or 5+2 (as in 2nd induction). Pts could receive hematopoietic cell transplantation (HCT) at the physician's discretion. Results AML-MRC was diagnosed in 246/309 (80%) enrolled pts (123 pts/arm). More AML-MRC pts achieved CR+CRi with CPX-351 (59/123 [48%] vs 40/123 [33%]; odds ratio = 1.83 [95% CI: 1.09-3.09]). Median OS in pts with AML-MRC who achieved CR+CRi was longer with CPX-351 vs 7+3 (Figure 1). The HCT rate in AML-MRC pts with CR+CRi was 54% with CPX-351 vs 43% with 7+3 (relative risk = 1.18 [95% CI: 0.79-1.76]), and OS landmarked from the HCT date was longer with CPX-351 (Figure 2). The safety profile was similar between arms (Table 1), except CPX-351 was associated with longer recovery of neutrophils to ≥500/μL (35 vs 29 d) and platelets to ≥50,000/μL (37 vs 28 d) vs 7+3 in pts who received 1 induction. Conclusions CPX-351 improved median OS overall and OS landmarked from the HCT date vs 7+3 chemotherapy in AML-MRC pts who achieved CR+CRi. The CPX-351 safety profile in this subgroup was consistent with the overall study population and known profile of 7+3.