Lenalidomide maintenance after initial immunochemotherapy in chronic lymphocytic leukaemia-Final analysis of the international phase III CLL6 RESIDUUM study of the ALLG and FILO groups.

Most patients treated for chronic lymphocytic leukaemia (CLL) fail to achieve measurable residual disease (MRD) negativity. The role of maintenance with the immunomodulatory drug lenalidomide in these patients is unclear. A randomised multicentre phase III trial (ACTRN12610000060044) was conducted in Australia and France to assess the effect of 2 years of daily lenalidomide maintenance versus observation in patients with CLL and residual disease after initial immunochemotherapy. The primary end-point was time to disease progression or death from randomisation. Between May 2011 and January 2018, 143 patients were randomised to receive lenalidomide (n = 71) or observation (n = 72). Median progression-free survival (PFS) was longer with lenalidomide at 64.6 months (95% confidence interval [CI] 47.7 to not reached) versus 42.4 months (95% CI 32.3-61.6) in the observation arm (p = 0.039). Lenalidomide benefit persisted for 3 years after maintenance cessation. There was no difference in overall survival. More patients taking lenalidomide achieved MRD negativity, especially those who received at least 20 maintenance cycles. Lenalidomide led to more cytopenias, infections and gastrointestinal effects. There were no cases of acute lymphoblastic leukaemia. In patients with CLL selected by the presence of residual disease at the end of initial chemoimmunotherapy, lenalidomide maintenance increased the chance of achieving MRD negativity and prolonged PFS.