Statins for Preventing Progression of Disease in Patients with Clonal Cytopenia of Undetermined Significance or Lower-risk Myelodysplastic Syndrome

Inclusion Criteria

• 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 cytopenia in at least one lineage: ** Hemoglobin < 12 g/dL in females or < 13 g/dL in males ** ANC < 1.8 x 10^9/L ** Platelets < 150 x 10^9/L * MDS is defined using the World Health Organization (WHO) 2016 definition and classified into lower-risk if Revised International Prognostic Scoring System (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 Institutional Review Board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable)

Exclusion Criteria

• CCUS patients with a cytogenetic change alone
• 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 enrollment
• 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 of active disease
• 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
• 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
• Uncontrolled intercurrent illness including, but not limited to, symptomatic infection, sepsis, or active liver disease (acute liver failure, decompensated cirrhosis, or persistent elevation in alanine transaminase [ALT] or aspartate aminotransferase [AST] > 3 x the upper limit of normal [ULN]), or any other comorbidity that would preclude statin use based on Food and Drug Administration (FDA) recommendation
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry
• Patients with human immunodeficiency virus (HIV) and hepatitis C virus (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