Lenalidomide Maintenance Therapy in Multiple Myeloma: A Phase II Clinical and Biomarker Study

Background: Multiple myeloma (MM) remains largely an incurable disease with an estimated median survival of 6-7 years in standard risk myeloma and 2-3 years in high risk disease despite treatment with autologous stem cell transplantation (ASCT). Maintenance therapy to achieve sustained suppression of residual disease following chemotherapy or ASCT has long been viewed as a desirable approach for extending survival in MM. Giving the immunomodulatory drug lenalidomide after induction or re-induction treatment may stimulate the immune system in various ways to stop or slow the return of cancer. It is not yet known how immune stimulatory effects of extended dosing with lenalidomide in the maintenance setting correlate with clinical benefits. Objectives: Assess T cell (cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), natural killer T cell (NKT) and normal killer (NK) cell numbers in peripheral blood during the course of lenalidomide maintenance therapy in treated MM patients. Eligibility: Patients with multiple myeloma who have achieved stable disease or better response, assessed at greater than or equal to 4 weeks after completing induction or re-induction treatment Age greater than or equal to 18 years Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-2 Adequate hematological parameters defined by: absolute neutrophil count greater than or equal to 1.0 K/microL, hemoglobin greater than or equal to 8 g/dL, and platelet count greater than or equal to 75 K/microL Adequate hepatic function, with bilirubin < 1.5 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times ULN Adequate renal function with creatinine clearance (CrCl) of greater than or equal to 40 mL/min. CrCl will be calculated using the Cockcroft-Gault method. If the calculated CrCl based on Cockcroft-Gault method is <40 mL/min, patient will have a 24 hr urine collection to measure CrCl. The measured CrCl must also be greater than or equal to 40 ml/min Design: Single arm, single stage, phase II trial of lenalidomide maintenance for treated MM patients who have stable or responsive disease. After screening, eligibility determination, and enrollment; subjects will receive lenalidomide 10 mg by mouth daily on days 1-21 of repeated 28-day cycles. When necessary, lenalidomide will be held and restarted in accordance with accepted clinical dose modification guidelines. Subjects may continue lenalidomide until disease progression or unacceptable toxicity or completion of two years of lenalidomide therapy and the 30 day safety follow-up visit. Blood will be obtained to assess changes in T cell (CD4, CD8), NKT and NK cell numbers by flow-cytometric analysis at pre-specified time points during lenalidomide maintenance. Blood samples and/or bone marrow samples where possible, will be used for additional research studies, which may include functional analyses of immune-cell subsets, analyses for cytokines, chemokines, antibodies, tumor cell antigen targets, and/or other markers.