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

Abstract

Introduction t-AML arises from prior cytotoxic therapy, ionizing radiotherapy, or immunosuppressive therapy for an unrelated disease and is associated with poorer outcomes relative to de novo AML, with a median overall survival (OS) of ∼6 mo following conventional 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 t-AML or AML with myelodysplasia-related changes. In a phase 3 study (NCT01696084) in older patients (pts; 60-75 y) with newly diagnosed high-risk/secondary AML, CPX-351 significantly improved OS vs 7+3, with a comparable safety profile. Objectives An exploratory analysis of the phase 3 study compared outcomes in the subgroup of pts with t-AML 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/day continuously for 7 d [2nd induction: 5 d] + D 60 mg/m2 on Days 1-3 [2nd induction: Days 1-2]). Pts achieving CR+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 t-AML was diagnosed in 63/309 (20%) enrolled pts; 14/30 (47%) receiving CPX-351 and 12/33 (36%) receiving 7+3 achieved a CR+CRi (odds ratio = 1.53 [95% CI: 0.56-4.20]). Fewer pts with CR+CRi after CPX-351 vs 7+3 had received prior non-anthracycline chemotherapy alone (CPX-351: 2 [14%] vs 7+3: 5 [42%]), whereas prior radiation therapy alone was less frequent in 7+3 pts (5 [36%] vs 2 [17%]). Median OS was longer for CPX-351 vs 7+3 in t-AML pts with CR+CRi (Figure 1). The HCT rate in pts with CR+CRi was similar for CPX-351 and 7+3 (57% vs 58%; relative risk = 0.97 [95% CI: 0.50-1.90]); however, OS landmarked from the HCT date was longer for CPX-351 (Figure 2). No pt relapsed prior to HCT. Median OS in pts with CR+CRi but no HCT was not reached for CPX-351 vs 8.48 mo for 7+3. The safety profile of CPX-351 vs 7+3 is shown in Table 1. Conclusions Among t-AML pts who achieved CR+CRi, CPX-351 improved median OS overall and OS landmarked from the HCT date vs 7+3. The CPX-351 safety profile in this subgroup was generally consistent with the known profile of 7+3.