Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by clonal proliferation of myeloid precursor cells, leading to bone marrow failure and severe cytopenias. Intensive chemotherapy, traditionally the 7+3 cytarabine/daunorubicin regimen, remains the standard of care, despite significative treatment-related toxicity and increased infectious risk. CPX-351, a liposomal formulation of cytarabine/daunorubicin delivered at a fixed synergistic ratio (1:5), has demonstrated improved survival over conventional regimens in patients with therapy-related AML and AML with myelodysplasia-related changes, leading to its regulatory approval. However, despite these benefits, safety considerations remain clinically important. Prolonged myelosuppression associated with CPX-351 may delay hematopoietic recovery and increase susceptibility to infectious complications, emphasizing the need for a comprehensive safety evaluation. To synthesize available evidence on infectious and hematologic adverse events in patients with AML treated with CPX-351. PubMed, Embase, and the Cochrane Library were searched from database inception up to January 2026. Outcomes included infectious complications (febrile neutropenia, bacteremia and sepsis) and hematologic adverse events (prolonged neutrophil and/or platelet recovery), graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 3. A random-effects model was used to pool risk ratios (RRs), with corresponding 95% confidence intervals (CIs). Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool for randomized controlled trials (RTCs), and certainty of evidence was evaluated according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. Four RCTs were included, comprising a total of 749 patients. Of these, 424 patients received CPX-351, while the remaining were assigned to standard chemotherapy regimens. Two studies were phase II trials, and two were phase III trials. Pooled analysis showed that CPX-351 was not associated with a higher risk of infectious-related events, with no significant differences in the incidence of febrile neutropenia (RR 1.17, 95% CI 0.89–1.54), bacteremia (RR 1.07, 95% CI 0.65–1.75) or sepsis (RR 0.99, 95% CI 0.61 – 1.59). Hematologic outcomes, namely neutrophil and platelet recovery, could not be pooled, but suggested a trend towards delayed hematopoietic recovery in the CPX-351 arm. Neutrophil recovery was consistently delayed with CPX-351 across all four studies (37 vs. 28 days; 36 vs. 32 days; 42 vs. 34 days; and 32 vs. 30 days). Similarly, platelet recovery occurred later with CPX-351 (36 vs. 32 days; 37 vs. 28; 45 vs. 35 days; and 34 vs. 29 days). In the risk of bias evaluation, one study was judged to be at low risk of bias, while three studies were assessed as having some concerns. GRADE assessment rated the certainty of evidence as low to very low, primarily due to differences in study populations and the limited number of studies, which represent key limitations of this review. Overall, CPX-351 was not associated with an increased risk of infectious complications compared to standard chemotherapy; however, it may be associated with a delayed hematopoietic recovery. These findings highlight the importance of vigilant supportive care and further real-world data to better characterize its hematologic safety profile.
Santos et al. (Sun,) studied this question.