Phase II, multicenter, randomized, open label trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus cytarabine and daunorubicin in patients with untreated AML 60-75 years of age.
ABSTRACT CPX-351 is a liposomal formulation of cytarabine:daunorubicin designed to deliver synergistic drug ratios to leukemia cells. In this Phase II study newly diagnosed older AML patients were randomized 2:1 to first-line CPX-351 or 7+3 treatment. The goal was to determine efficacy and identify patient subgroups that may benefit from CPX-351 treatment. Response rate (CR+CRi) was the primary endpoint, with event-free survival (EFS) and overall survival (OS) as secondary endpoints. The 126 patients entered were balanced for disease and patient-specific risk factors. Overall, CPX-351 produced higher response rates (66.7%vs.51.2%, P=0.07), meeting predefined criteria for success (P<0.1). Differences in EFS and OS were not statistically significant. A planned analysis of the secondary AML subgroup demonstrated an improved response rate (57.6% vs.31.6%, P=0.06), and prolongation of EFS (HR=0.59, P=0.08) and OS (HR=0.46, P=0.01). Recovery from cytopenias was slower following CPX-351 (median days to ANC≥1000: 36vs.32; Platelets >100K: 37vs.28) with more grade 3-4 infections but without increase in infection-related deaths (3.5%vs.7.3%) or 60-day mortality (4.7% vs.14.6%) indicating acceptable safety. These results suggest clinical benefit with CPX-351, particularly among patients with secondary AML and provide the rationale for a Phase III trial currently underway in newly diagnosed secondary AML patients. This study was registered at Clinicaltrials.gov, identifier: NCT00788892.
- SourceAvailable from: Sacha Satram-Hoang[Show abstract] [Hide abstract]
ABSTRACT: Over half of patients diagnosed with acute myeloid leukemia (AML) are 65 years or older. We examined patient characteristics, treatment patterns, and survival among elderly patients in routine clinical practice. We utilized a retrospective cohort analysis of first primary AML patients in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Patients were diagnosed between January 1, 2000 and December 31, 2009, >66 years, and continuously enrolled in Medicare Part A and B in the year prior to diagnosis. Kaplan-Meier curves and Cox proportional hazards regression assessed overall survival by treatment. There were 3327 (40 %) patients who received chemotherapy within 3 months of diagnosis. Treated patients were more likely younger, male, and married, and less likely to have secondary AML and poor performance indicators and comorbidity score compared to untreated patients. In multivariate survival analysis, treated patients exhibited a significant 33 % lower risk of death compared to untreated patients. Significant survival benefits were noted with receipt of intensive and hypomethylating agent (HMA) therapies compared to no therapy. A survival benefit with allogeneic hematopoietic stem cell transplantation was seen in younger Medicare patients. This real-world study showed that about 60 % of elderly AML patients remain untreated following diagnosis. Use of anti-leukemic therapy was associated with a significant survival benefit in this elderly cohort.Annals of Hematology 03/2015; 94(7). DOI:10.1007/s00277-015-2351-x · 2.40 Impact Factor
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ABSTRACT: Recent advances in molecular technology have unraveled the complexity of leukemogenesis and provided the opportunity to design more personalized and pathophysiology-targeted therapeutic strategies. Despite the use of intensive chemotherapy, relapse remains the most common cause for therapeutic failure in acute myelogenous leukemia (AML). The interactions between leukemia stem cells (LSC) and marrow microenvironment appear to be critical in promoting therapeutic resistance through progressive acquisition of genetic and epigenetic changes within leukemia cells and immune evasion, resulting in leukemia cell survival. With advances in genomic sequencing efforts, epigenetic and phenotypic characterization, personalized therapeutic strategies aimed at critical leukemia survival mechanisms may be feasible in the near future. Here, we review select novel approaches to therapy of AML such as targeting LSC, altering leukemia/marrow microenvironment interactions, inhibiting DNA repair or cell cycle checkpoints, and augmenting immune-based anti-leukemia activity.Clinical Cancer Research 10/2014; DOI:10.1158/1078-0432.CCR-14-0900 · 8.19 Impact Factor
Article: Progress in Acute Myeloid Leukemia[Show abstract] [Hide abstract]
ABSTRACT: Significant progress has been made in the treatment of acute myeloid leukemia (AML). Steady gains in clinical research and a renaissance of genomics in leukemia have led to improved outcomes. The recognition of tremendous heterogeneity in AML has allowed individualized treatments of specific disease entities within the context of patient age, cytogenetics, and mutational analysis. The following is a comprehensive review of the current state of AML therapy and a roadmap of our approach to these distinct disease entities.Clinical Lymphoma, Myeloma and Leukemia 09/2014; 15(3). DOI:10.1016/j.clml.2014.08.006 · 1.93 Impact Factor