Anjali S. Advani from Taussig Cancer Institute, Cleveland, OH, and colleagues conducted a phase II trial (NCT00840177), investigating the efficacy of high dose pravastatin, a cholesterol lowering agent, in combination with idarubicin and cytarabine in Relapsed/Refractory (R/R) AML patients with poor risk cytogenetics and poor risk molecular mutations. The results of the study were published on 25 January 2018 in Leukemia Research.
In this study, a total of 46 R/R AML patients (median age = 57 years [range 23 – 75]) who were in Complete Remission (CR) or CR with incomplete bone marrow recovery (CR/CRi) following the most recent chemotherapy < 6 months were enrolled and treated at SWOG institutions between April 2013 – November 2014. Patients were administered pravastatin (1280 mg orally) on Days 1–8, idarubicin (12 mg/m2/day) on Days 4–6, and cytarabine (1.5 g/m2/day) on Days 4–7. For this study to be considered sufficiently efficient, ≥ 12 patients should achieve CR/CRi of the first 37 patients accrued.
- CR/CRi rate: 30%
- Median Overall Survival (OS): 4.1 months
- Eleven patients proceeded to allogeneic Hematopoietic Stem Cell Transplant (HSCT)
- Median OS for patients proceeding to allogeneic HSCT: 27.1 months
- Median relapse free survival = 2.6 months (range 0.5 – 12.8 months)
- The most common Grade 3–5 non-hematologic AEs were febrile neutropenia (n = 31), bacteremia (n = 11), lung infection (n = 8), diarrhea (n = 9)
In this study, the CR/CRi rate in poor-risk R/R AML patients did not fulfil all the criteria for a positive study (P = 0.062) but the authors noted that the results of the study are still encouraging especially in a R/R AML population. They further added that “targeting the cholesterol pathway may have therapeutic impact” and thus further studies are required.
Key limitations highlighted by the authors include the small sample size and “uncontrolled structure” of the study. Thus they suggested that a randomized phase II study with chemotherapy versus chemotherapy plus pravastatin is required.