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Better outcomes after allogeneic hematopoietic cell transplantation with CPX-351 induction in older AML patients

An exploratory analysis from a phase III study demonstrated that CPX-351, a liposomal formulation of cytarabine and daunorubicin, results in better outcomes after an allogeneic hematopoietic cell transplantation (HCT) in older patients with high-risk acute myeloid leukemia (AML) compared with standard cytarabine and daunorubicin. With CPX-351, 53% fewer deaths were reported within 100 days after transplantation. These results suggest that CPX-351 may provide an effective bridge to a successful HCT for a subgroup of AML patients with a very poor prognosis.

Compared to younger patients, AML patients older than 60 years of age have lower remission rates with increased induction mortality when they are treated with intensive induction chemotherapy. CPX-351 (Vyxeos) is a liposomal formulation of cytarabine and daunorubicin encapsulated at a 5:1 molar ratio. Previously reported results from a phase III, randomized, open-label study of CPX-351 vs. 7+3 cytarabine and daunorubicin in newly diagnosed, older patients with secondary AML already suggested superior survival for patients treated with CPX-351 (median OS 9.56 vs. 5.59 months; HR: 0.69; p= 0.005). During ASH 2016, an exploratory analysis was presented of patients who received an allogeneic HCT after induction treatment. The aim of this analysis was to assess the effect of HCT on the outcome by arm. This is of interest given the fact that only a small minority of AML patients in this age range can currently be cured with chemotherapy alone.

The phase III study at hand included 309 patients with newly diagnosed secondary AML, aged 60 to 75 years, with a history of prior cytotoxic treatment, antecedent myelodysplastic syndrome (MDS) (with or without prior treatment with hypomethylating agents), or AML with WHO–defined MDS-related cytogenetic abnormalities. Patients in the study were randomized to receive either CPX-351 induction (100 units/m2 [100 mg/m2 cytarabine and 44 mg daunorubicin mg/m2] on days 1, 3, and 5 [first induction only]), or standard 7+3 induction (cytarabine 100 mg/m2/day x 7 days plus daunorubicin 60 mg/m2 on days 1, 2, and 3 [first induction] or x 5 days [reinduction/consolidation] plus daunorubicin 60 mg/m2 on days 1 and 2).

In total, 153 patients were randomized to the CPX-351 and 156 patients received 7+3 induction. Patients in either arm responding to induction with a complete response (CR) or a CR with incomplete platelet or neutrophil recovery (N=125) were considered for an allogeneic HCT when possible. In total, 91 patients were transplanted: 52 (34%) from the CPX-351 arm and 39 (25%) from the 7+3 arm. Patient and AML characteristics were similar according to randomized arm (Slide 2). However, the CPX-351 arm contained a higher percentage of older patients (70 years or older) who were transplanted (31% with CPX-351, vs. 15% with 7+3).

The mortality rate 100 days post-transplant was 9.6% for patients in the CPX-351 arm as compared to 20.5% in the 7+3 arm. The main causes of death within 100 days after the HCT were refractory AML (3.8% with CPX-351, 7.7% with 7+3), graft-versus-host disease (3.8% with CPX-351, 2.6% with 7+3) and renal, respiratory, multi-organ failure, or septic shock (none with CPX-351, 2.6% for each with 7+3). A landmark survival analysis from the time of HCT transplantation (N=91) demonstrated a markedly better OS for patients treated with CPX-351 (median OS not reached with CPX-351 vs. 10.25 months for 7+3; HR: 0.46; p=0.0046). The cox proportional hazards HR, including transplant as a time‐dependent covariate, was shown to be 0.51 (95%CI: 0.35–0.75; p=0.0007), in favor of CPX‐351.

In summary, the outcomes after allogeneic transplant in older patients with high‐risk AML appear to be superior in patients treated with CPX‐351. These results should however be interpreted with caution given the fact that this was an exploratory analysis of a non‐randomized subgroup. Nevertheless, based on these data, CPX‐351 may provide a bridge to successful transplant in a poor‐risk subgroup of AML patients. With CPX-351 a lower induction‐related morbidity and mortality was seen indicating that patients may be transplanted in better condition. Also the disease control was better with CPX-351 leading to more patients being transplanted in CR.


Lancet J, Hoering A, Uy G et al. Survival Following Allogeneic Hematopoietic Cell Transplantation in Older High-Risk Acute Myeloid Leukemia Patients Initially Treated with CPX-351 Liposome Injection Versus Standard Cytarabine and Daunorubicin: Subgroup Analysis of a Large Phase III Trial. Presented at ASH 2016; Abstract 906.

Speaker Jeffrey Lancet


Jeffrey Lancet, MD;
Department of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA


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