Healthcare resource utilization in a phase 3 study of CPX-351 in patients with newly diagnosed high-risk/secondary acute myeloid leukemia.

Aims: Treatment of acute myeloid leukemia (AML) requires significant healthcare resource utilization (HRU), including lengthy hospitalizations. In a phase 3 study (NCT01696084), CPX-351 (Vyxeos) showed significant benefits to overall survival and complete remission versus conventional 7 + 3 cytarabine/daunorubicin. This analysis evaluated HRU in patients aged 60-75 years with newly diagnosed high-risk/secondary AML treated with CPX-351 versus 7 + 3 in the phase 3 study.Materials and methods: Patients were randomized to receive up to two induction cycles with CPX-351 or 7 + 3. Responders could receive up to two cycles of consolidation. To normalize HRU to length of treatment, patients were assessed on a per patient-year (PPY) basis. HRU analyses included hospital and intensive care unit (ICU) stays, anti-infective use, transfusions, and white blood cell colony-stimulating factor (CSF).Results: The median (range) total duration of hospitalization was 39 (3-110) days with CPX-351 (n = 153) and 32 (2-83) days with 7 + 3 (n = 151); the estimated durations of hospitalization PPY were 198.4 and 240.5 days, respectively. The median (range) total duration of ICU stays was 0 (0-45) days with CPX-351 and 0 (0-17) days with 7 + 3; the estimated durations of ICU stays PPY were 6.7 and 10.5 days, respectively. When comparing supportive care use during CPX-351 and 7 + 3 treatment, the estimated number PPY of bags of platelets used (24.6 vs 26.9, respectively), bags of packed red blood cells used (13.0 vs 13.9), days of anti-infectives (162.0 vs 159.2), and days of CSF (4.0 vs 2.4) were not notably different.Limitations: This clinical study analysis may not represent real-world HRU patterns or be generalizable to a broader AML population.Conclusions: These PPY data, showing shorter durations of hospitalization and similar use of supportive care with CPX-351 versus 7 + 3, suggest CPX-351 is not associated with increased HRU in older patients with newly diagnosed high-risk/secondary AML.

Final safety and efficacy results from the CPX-351 early access program for older patients with high-risk or secondary acute myeloid leukemia.

CPX-351, a dual-drug liposomal encapsulation of cytarabine and daunorubicin at a synergistic 5:1 molar drug ratio, achieved superior efficacy compared with conventional chemotherapy in older adults with newly diagnosed, high-risk/secondary acute myeloid leukemia (AML) in phase 2 and 3 studies. Prior to CPX-351 commercialization, an expanded access program (EAP) provided CPX-351 access for this population in the United States. In this phase 4, single-arm, open-label study (NCT02533115), 52 patients were treated with CPX-351 for 1-2 induction cycles and ≤4 consolidation cycles. The primary endpoint was safety. The most common serious adverse events were febrile neutropenia (19%), pneumonia (10%), and infection (8%). The 30- and 60-d mortality rates were 0% and 6%, respectively. Remission was achieved by 44% of patients; 90% of patients were alive at study completion. Overall, these results support outcomes from prior studies and the use of CPX-351 in older adults with newly diagnosed, high-risk/secondary AML.

Consolidation outcomes in CPX-351 versus cytarabine/daunorubicin-treated older patients with high-risk/secondary acute myeloid leukemia.

CPX-351 is a dual-drug liposomal encapsulation of cytarabine/daunorubicin. In a phase 3 study (ClinicalTrials.gov Identifier: NCT01696084), patients aged 60-75 years with newly diagnosed, high-risk/secondary AML received 1-2 induction cycles with CPX-351 or 7 + 3 chemotherapy; those achieving complete remission (including with incomplete platelet or neutrophil recovery) could receive up to 2 consolidation cycles with CPX-351 or 5 + 2 chemotherapy, respectively. In this exploratory analysis of the subgroup of patients who received consolidation, median overall survival was prolonged among patients receiving CPX-351 induction/consolidation versus 7 + 3/5 + 2 (25.43 vs. 8.53 months; HR = 0.44 [95% CI: 0.25-0.77]). The safety profile of CPX-351 consolidation was consistent with that of the overall study. Outpatient administration of CPX-351 consolidation occurred in 51%-61% of patients and did not diminish overall survival. These findings suggest consolidation with CPX-351 in this patient population contributed to the prolonged overall survival versus 7 + 3/5 + 2, building upon findings from the overall study population, and provide evidence that, with careful monitoring, some patients can successfully receive CPX-351 as outpatients.

CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia.

Purpose CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells. Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus daunorubicin chemotherapy (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). Patients and Methods In this open-label, randomized, phase III trial, 309 patients age 60 to 75 years with newly diagnosed high-risk/sAML received one to two induction cycles of CPX-351 or 7+3 followed by consolidation therapy with a similar regimen. The primary end point was overall survival. Results CPX-351 significantly improved median overall survival versus 7+3 (9.56 v 5.95 months; hazard ratio, 0.69; 95% CI, 0.52 to 0.90; one-sided P = .003). Overall remission rate was also significantly higher with CPX-351 versus 7+3 (47.7% v 33.3%; two-sided P = .016). Improved outcomes were observed across age-groups and AML subtypes. The incidences of nonhematologic adverse events were comparable between arms, despite a longer treatment phase and prolonged time to neutrophil and platelet count recovery with CPX-351. Early mortality rates with CPX-351 and 7+3 were 5.9% and 10.6% (two-sided P = .149) through day 30 and 13.7% and 21.2% (two-sided P = .097) through day 60. Conclusion CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML. The safety profile of CPX-351 was similar to that of conventional 7+3 therapy.

Burden of Acute Myeloid Leukemia Among Older, Newly Diagnosed Patients: Retrospective Analysis of Data From the 2010-2012 Medicare Limited Data Set.

PURPOSE: Acute myeloid leukemia (AML) disproportionately affects older adults; the prognosis in this subpopulation is generally poor, with variable use of inpatient chemotherapy. This study characterizes treatment patterns, hospitalizations, and outcomes among older patients with AML. METHODS: Using the Centers for Medicare & Medicaid Services' 2010-2012 100% Limited Data Set (LDS), data from all hospital claims from fee-for-service Medicare beneficiaries between 60 and 75 years of age with newly diagnosed AML and ≥1 hospitalization were analyzed. FINDINGS: Among 3700 identified patients with AML, 1979 (53.5%) received chemotherapy. Hospitalization rates were highest initially and then declined over time, irrespective of chemotherapy use. The mean length of initial hospital stay was longer in patients receiving chemotherapy. Intensive care unit admissions occurred in 33% of initial hospitalizations. Factors associated with receiving chemotherapy included younger age, fewer comorbidities, and the absence of prior hematologic disorders. Chemotherapy was associated with significantly increased survival compared with no chemotherapy (P < 0.0001). IMPLICATIONS: AML in older patients is associated with frequent hospitalizations and intensive care unit admissions. New treatment options with more favorable risk-to-benefit profiles are needed in this population.