PF393 A RANDOMISED JOINT AUSTRALASIAN (ALLG) AND FRENCH (FILO) STUDY OF LENALIDOMIDE CONSOLIDATION IN PATIENTS WITH RESIDUAL CLL AFTER FRONT‐LINE TREATMENT WITH FC/FCR (THE CLL6 TRIAL)

Abstract

Background:Patients with residual disease following front‐line treatment of chronic lymphocytic leukemia with FCR chemotherapy have reduced progression free and overall survival. In patients with very high risk disease (minimal residual disease (MRD) >10–2 or 10–2 to 10–4 plus high risk genetics), lenalidomide improves progression free survival (PFS), possibly with an increased risk of acute lymphoblastic leukemia (ALL). The CLL6 RESIDUUM trial is a joint trial of the Australasian Leukaemia and Lymphoma Group (ALLG) and the French Innovative Leukemia Organization (FILO) that analyzes the role of 2 years lenalidomide consolidation therapy in patients undergoing front‐line treatment for CLL who do not enter MRD negative complete remission.Aims:To determine whether lenalidomide consolidation improves PFS in patients with residual CLL after front‐line treatment for CLL.Methods:Eligibility criteria were CLL patients requiring front‐line treatment by iwCLL criteria with identifiable residual disease (including those with only minimal residual disease in blood or bone marrow >10–4 identified by multiparameter flow cytometry (MFC) after 6 cycles (minimum 4) of fludarabine, cyclophosphamide, rituximab (FCR). Following completion of treatment, those with clinical, radiological or MFC evidence of residual leukemia were randomized in a 1:1 ratio to receive two years of maintenance treatment with lenalidomide 10 mg daily (len) or observation (obs). Patients were reviewed for evidence of clinical progression, and peripheral blood and bone marrow were sampled regularly for evidence of MRD. The primary end point of the study was time to progression free survival (PFS) or death.Results:Between November 2011 and January 2018, 143 patients with residual disease after completing front‐line FCR chemotherapy were randomized to either len (n = 71, 49.7%) or obs (n = 72, 50.3%). Patients were well matched between the two arms for gender (len 80% male; obs 78% male), age at randomization (len 60.9 ± 9.1 years; obs 60.1 ± 9.7 years), number of prior FCR cycles (len 4/5/6 30/1/69%; obs 24/11/64%) and response to chemotherapy CR/nPR/PR (len 38/13/49%; obs 31/14/55%). Median follow up in the len arm was 24.6 months and in the obs arm 25.9 months. For the entire cohort, at median follow up of 25.4 months (0.9 to 73.2), there were 6 deaths (4.2%) and 36 progression events (25.2%) recorded. Deaths were equally distributed (3 in each arm) (p = 0.97). There were 14 progressions in the len arm and 22 in the obs arm (p = 0.21). The median PFS in the overall cohort was 53.9 months (95% CI: 49.0 to NR). Median PFS was 53.9 months (95% CI: 36.8 to NR) in the len arm and 62.5 (95% CI: 46.3 to NR) in the obs arm (p = 0.26) (Figure 1). Therapy was generally well tolerated. There was a higher incidence of leucopenia and respiratory infection in the len arm. One death due to cancer was recorded in each arm. No cases of ALL were observed during treatment or in follow up.Summary/Conclusion:In this trial in patients with residual CLL after front‐line FCR, lenalidomide consolidation did not improve PFS in either the entire group or in subgroups of patients based on peripheral blood or bone marrow MRD or on remission status at baseline. Further analysis of cytogenetic risk factors will be performed to determine if lenalidomide had an effect on PFS in high risk populations.image