Selinexor and Lenalidomide for Consolidation and Maintenance Treatment in Multiple Myeloma Post-transplant

Inclusion Criteria:

• Patients ≥18 years of age at time of enrollment.

• Ability to understand and willingness to sign an IRB approved written informedconsent document (or that of legally authorized representative, if applicable).

• Histologically confirmed diagnosis of multiple myeloma that is symptomatic. Patientswith multiple myeloma with local amyloid deposition in the bone marrow are eligible.

• Patients must have undergone lenalidomide-based induction regimen.

• Patient must have undergone AHCT within 80 to 140 days prior to C1D1 for MM.

• Patient must be MRD-positive (per 10^-5 threshold) using clonoSEQ MRD® assay on bonemarrow biopsy prior to study enrollment.

• Patient must have achieved very good partial response or better per IMWG responsecriteria prior to study enrollment.

• Eastern Cooperative Oncology Group (ECOG) performance status and/or otherperformance status 0, 1, or 2.

• Adequate organ function as defined below:

• Absolute neutrophil count (ANC) ≥ 1.5 K/cumm.

• Platelet count ≥ 100 K/cumm (patients for whom <50% of bone marrow nucleatedcells are plasma cells) or ≥50 K/cumm (patients for whom ≥50% of bone marrownucleated cells are plasma cells).; platelet transfusions to help patients meeteligibility criteria are not allowed within 7 days before C1D1.

• Hemoglobin ≥ 8.5 g/dL without blood transfusion within 7 days before C1D1.

• Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN), patientswith Gilbert's syndrome must have a total bilirubin of < 3 x ULN.

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 xULN.

• Calculated creatinine clearance ≥ 15 mL/min per Cockcroft and Gault formula.

• Women of childbearing potential must follow pregnancy testing requirements asoutlined in the Revlimid REMS® program material. This is defined as eithercommitting to continued abstinence from heterosexual intercourse or beginning TWOacceptable methods of contraception (one highly effective method and one additionaleffective method AT THE SAME TIME) at least 28 days prior to the start oflenalidomide, for the duration of study participation, and for 28 days following thelast dose of lenalidomide. Women of childbearing potential must also agree toongoing pregnancy testing.

• Men must agree to use a latex condom during sexual contact with a woman ofchildbearing potential even if they have had a successful vasectomy. All patientsmust be counseled at a minimum of every 28 days about pregnancy precautions andrisks of fetal exposure. Should a woman become pregnant or suspect she is pregnantwhile participating in this study, she must inform her treating physicianimmediately.

• All study participants must be registered into the mandatory Revlimid REMS® programand be willing to comply with its requirements. Per standard Revlimid REMS® programrequirements, all physicians who prescribe lenalidomide for research subjectsenrolled into this trial, must be registered in, and must comply with, allrequirements of the Revlimid REMS® program.

Exclusion Criteria:

• Patients with lenalidomide-refractory disease during induction.

• Prior receipt of selinexor or another XPO1 inhibitor previously.

• Female patients who are lactating or have a positive serum pregnancy test during thescreening period.

• Evidence of MM disease progression any time prior to enrollment. Progression fromsmoldering/asymptomatic MM to symptomatic MM is not exclusionary.

• Tandem autologous transplantation.

• History of plasma cell leukemia or MM CNS involvement.

• Administration or planned administration of any other concomitant chemotherapy,immunotherapy, radiotherapy, or any ancillary therapy which would be considered atreatment of multiple myeloma from Day +28 post-transplant through discontinuationfrom study. Patients may be on corticosteroids if they are being given for disordersother than multiple myeloma (e.g., adrenal insufficiency, rheumatoid arthritis,etc.).

• Any serious medical or psychiatric illness that could, in the investigator'sopinion, potentially interfere with the completion of treatment according to thisprotocol.

• Prior organ transplant requiring immunosuppressive therapy.

• Subjects with active hepatitis B virus (Hep B) are allowed if antiviral therapy forhepatitis B has been given for >8 weeks and viral load is <100 IU/ml prior to firstdose of trial treatment. Subjects with untreated hepatitis C virus (HCV) areallowed. Subjects with Human Immunodeficiency Virus (HIV) who have CD4+ T-cellcounts ≥ 350 cells/µL and no history of AIDS-defining opportunistic infections inthe last year are allowed.

• Known allergy to any of the study medications, their analogues, or excipients in thevarious formulations of any agent.

• Known intolerance, hypersensitivity, or contraindication to glucocorticoids.

• Any active gastrointestinal dysfunction interfering with the patient's ability toswallow tablets, or any active gastrointestinal dysfunction that could interferewith absorption of study treatment.

• Concurrent hematologic or non-hematologic malignancy requiring treatment (other thanmultiple myeloma with local amyloid deposition in the bone marrow).

• Active, unstable cardiovascular function, as indicated by the presence of:

• Symptomatic ischemia, or

• Uncontrolled clinically significant conduction abnormalities (e.g. patientswith ventricular tachycardia on anti-arrhythmics are excluded; patients withfirst degree atrioventricular block or asymptomatic left anterior fascicularblock/right bundle branch block will not be excluded), or

• Congestive heart failure of NYHA Class ≥3 or known left ventricular ejectionfraction of <40%, or

• Myocardial infarction within 3 months prior to C1D1.

• Grade > 3 peripheral neuropathy, or Grade 2 with pain on clinical examination duringthe screening period.

• Major surgery within 14 days prior to C1D1.

• Uncontrolled active infection requiring parenteral antibiotics, antivirals, orantifungals within 1 week prior to C1D1. Patients on prophylactic antibiotics orwith a controlled infection within 1 week prior to C1D1 are acceptable.

• Participation in other clinical trials, including those with other investigationalagents not included in this trial, within 30 days prior to C1D1 and throughout theduration of this trial.