TREATMENT WITH COMBINATION OF LENALIDOMIDE AND RITUXIMAB ACHIEVES DURABLE RESPONSES IN A LONG TERM FOLLOW UP OF PATIENTS WITH INDOLENT NON‐HODGKIN'S LYMPHOMA

Abstract

Introduction: Standard front line treatment for indolent nonhodgkin's lymphoma (iNHL) is effective but is associated with short- and long-term toxicity, and many patients relapse within 5 years. Novel approaches targeting the immune microenvironment may provide alternative therapeutic strategies with improved outcomes. The immunomodulatory combination, lenalidomide with rituximab (R2), has been associated with high response rates and acceptable safety in iNHL (Fowler 2014), however, long-term outcomes regarding this approach are lacking. We report the mature follow up of patients treated with lenalidomide-rituximab on a phase II clinical trial. Method(s): We conducted a phase II study of R2 in untreated iNHL. Lenalidomide was given orally at 20 mg/day on days 1-21 of all 28-day cycles for follicular lymphoma (FL) and marginal zone lymphoma (MZL). In small lymphocytic lymphoma (SLL), dose began at 10 mg/ day to avoid tumor flare. Rituximab was given at 375 mg/m2 on day 1 of each cycle. Patients responding after 6 cycles could continue therapy for up to 12 cycles. Tumor assessment (CT and physical exam) was performed at study entry, every 3 months for 2 years, every 6 months in year 3, and then annually. Patients were monitored for long-term toxicity and secondary cancers. Result(s): All 110 patients were enrolled between 6/2008 and 8/ 2011, and 103 were evaluable for response assessment. At data cut, median follow up was 7.2 years. The 5-year progression free survival in FL, MZL and SLL is 65% (95% CI, 0.53-0.81), 48% (95% CI, 0.32-0.73) and 50% (95% CI, 0.35-0.72), respectively. Median progression free survival has not been reached in the FL subset. No unexpected late toxicities were observed. Ten secondary malignancies were reported (two localized skin cancers), and only one case of aggressive transformation has occurred. Seven deaths were reported during follow up. (Figure Presented) Conclusion(s): Lenalidomide plus rituximab is highly effective and well tolerated as initial treatment for iNHL and produces durable responses with few late effects, particularly in FL. An international phase 3 study (NCT01476787) is ongoing comparing this regimen to chemotherapy in untreated follicular lymphoma. (Table Presented).