Report of the relapsed/refractory cohort of SWOG S0919: A phase 2 study of idarubicin and cytarabine in combination with pravastatin for acute myelogenous leukemia (AML). (April 2018)

• Record Type: Journal Article
• Authors: Advani, Anjali S.; Li, Hongli; Michaelis, Laura C.; Medeiros, Bruno C.; Liedtke, Michaela; List, Alan F.; O'Dwyer, Kristen; Othus, Megan; Erba, Harry P.; Appelbaum, Frederick R.
• Is Part Of: Leukemia research. Volume 67(2018)
• Page Start: 17
• Page End: 20
• Publication Date: 2018-04
• Subjects: Acute myeloid leukemia -- Relapsed -- Refractory -- Pravastatin -- Idarubicin -- Cytarabine; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2018.01.021
• Languages: English
• ISSNs: 0145-2126

Abstract

Highlights: AML cells require high levels of cholesterol for survival. Targeting the cholesterol pathway represents a potential therapeutic option for AML. Pravastatin plus chemotherapy has activity in relapsed/refractory AML. Abstract: Inhibition of cholesterol synthesis and uptake sensitizes acute myeloid leukemia (AML) blasts to chemotherapy. A Phase 2 study of high dose pravastatin given in combination with idarubicin and cytarabine demonstrated an impressive response rate [75% complete remission (CR), CR with incomplete count recovery (CRi)]. However, this population was a favorable risk group as eligible patients had to have a CR/CRi lasting ≥3 months following their most recent chemotherapy. Therefore, the study was amended to treat patients with poor risk disease including those with CR/CRi <6 months following their last induction regimen or with refractory disease. Here, we present results in this poor risk group. This trial included a significant number of patients with poor risk cytogenetics (43%) and poor risk molecular mutations. The response rate was 30% and approximately one-fourth of patients were able to proceed to allogeneic hematopoietic stem cell transplant (HSCT). The median overall survival for patients proceeding to allogeneic HSCT is 27.1 months. Although this trial did not meet criteria for a positive study based on the response rate (p = .062), these results are encouraging given the poor risk population and suggest that targeting the cholesterol pathway may have therapeutic benefit in AML.