Statins in Patients With Clonal Cytopenia of Undetermined Significance (CCUS) and Myelodysplastic Syndromes (MDS)

Prior treatment

• Current or prior use of disease-modifying therapy (e.g., lenalidomide, Luspatercept, Imitelstat, HMAs, venetoclax) with any dose within the last 3 months, with the exception of concurrent use of erythropoetin stimulating agents
• Prior use of a statin within 1 year prior to start of treatment.
• Currently receiving any investigational agent for CCUS/MDS. The minimum interval between the last dose of investigational agent used for CCUS/MDS and Day 1 of this trial should be 5 half-lives of the investigational agent.
• Patients with HIV and HCV are not eligible for the trial if they are concomitantly receiving active treatment for HIV/HCV given the concern for potential drug interactions. The minimum interval between the last dose of antiviral and enrollment into the study should be 28 days or 5 half-lives of the antiviral drug, whichever is longer. The liver function profile of eligible HIV/HCV patients must be within the acceptable limits.

Other illness

• A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence active of disease.
• A history of allergic reactions or intolerance attributed to compounds of similar chemical or biologic composition to atorvastatin, rosuvastatin, any other statin, or other agents used in the study.

Lab values

• Uncontrolled intercurrent illness including, but not limited to, symptomatic infection, sepsis, or active liver disease (acute liver failure, decompensated cirrhosis, or persistent elevation in ALT or AST \> 3 x ULN), or any other comorbidity that would preclude statin use based on FDA recommendation.

Other

• CCUS patients with cytogenetic change alone.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.

• Diagnosis of CCUS or lower-risk MDS as defined below:
  • CCUS is defined as the presence of somatic mutation(s) in recurrently mutated genes identified through the clinical MyeloSeq assay with a VAF ≥ 2% in the absence of bone marrow morphology/cytogenetic changes diagnostic of MDS PLUS unexplained persistent cytopenia in at least one lineage for at least 6 months:
  • Hemoglobin \< 11.3 g/dL in females or \< 13 g/dL in males
  • ANC \< 1.8 x 109/L
  • Platelets \< 150 x 109/L
  • MDS is defined using the WHO 2016 definition and classified into lower-risk if IPSS-R score is ≤ 3.5 . Lower-risk MDS will be required to have at least one mutation in a recurrent mutated gene with a VAF ≥ 2%.
• Patient must be transfusion independent.
• At least 18 years of age.
• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).