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

Inclusion Criteria:

• Diagnosis of CCUS or lower-risk MDS as defined below:

• CCUS is defined as the presence of somatic mutation(s) in recurrently mutatedgenes identified through the clinical MyeloSeq assay with a VAF ≥ 2% in theabsence of bone marrow morphology/cytogenetic changes diagnostic of MDS PLUSunexplained 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 ifIPSS-R score is ≤ 3.5 . Lower-risk MDS will be required to have at least onemutation 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 informedconsent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

• CCUS patients with 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 theexception of concurrent use of erythropoetin stimulating agents

• Prior use of a statin within 1 year prior to start of treatment.

• A history of other malignancy with the exception of malignancies for which alltreatment was completed at least 2 years before registration and the patient has noevidence active of disease.

• Currently receiving any investigational agent for CCUS/MDS. The minimum intervalbetween the last dose of investigational agent used for CCUS/MDS and Day 1 of thistrial should be 5 half-lives of the investigational agent.

• A history of allergic reactions or intolerance attributed to compounds of similarchemical or biologic composition to atorvastatin, rosuvastatin, any other statin, orother agents used in the study.

• Uncontrolled intercurrent illness including, but not limited to, symptomaticinfection, sepsis, or active liver disease (acute liver failure, decompensatedcirrhosis, or persistent elevation in ALT or AST > 3 x ULN), or any othercomorbidity that would preclude statin use based on FDA recommendation.

• Pregnant and/or breastfeeding. Women of childbearing potential must have a negativepregnancy test within 14 days of study entry.

• Patients with HIV and HCV are not eligible for the trial if they are concomitantlyreceiving active treatment for HIV/HCV given the concern for potential druginteractions. The minimum interval between the last dose of antiviral and enrollmentinto the study should be 28 days or 5 half-lives of the antiviral drug, whichever islonger. The liver function profile of eligible HIV/HCV patients must be within theacceptable limits.