Long-term results of the Fondazione Italiana Linfomi (FIL) MCL0208 trial of lenalidomide maintenance versus observation after Autologous Stem Cell Transplantation (ASCT) in Mantle Cell Lymphoma (MCL) patients

The FIL MCL0208 phase III study compared lenalidomide maintenance (LEN) for 2 years to observation (OBS) after autologous stem cell transplantation in young (age <65 years) patients with previously untreated mantle cell lymphoma. LEN resulted in superior progression-free survival (PFS) but no overall survival (OS) benefit. The trial included a large minimal residual disease (MRD) sub-study, which was limited at early detection time points but highlighted the high prognostic value of both punctual and kinetic MRD analysis. Here, we provide the long-term clinical and molecular results at a median follow-up of 74 months from randomization. We observed PFS of 55% with LEN versus 50% with OBS (P=0.175) at 72 months. Time-varying effect modeling showed a PFS advantage in favor of LEN up to 36 months (P=0.04), with a subsequent decrease in PFS benefit. No long-term difference in OS was observed (P=0.819). At 60 months, the cumulative incidence of secondary malignancies was 9.4% [95% confidence interval 3.1-15.6] with LEN versus 4.5% [0.1-8.8] with OBS (P=0.219). Updated results showed a persistent increased risk of progression after MRD positivity in both bone marrow (hazard ratio 4.17 [2.70-6.44]) and peripheral blood (hazard ratio 2.64 [1.69-4.12]), even when considering the long-term follow-up, with persistent stability of kinetic models over time based on the accumulation of negative MRD results. Thus, the 2-year LEN program provided an initial PFS benefit that was not maintained when LEN was interrupted. The long-term MRD results emphasize the predictive value of this tool, particularly in the context of kinetic models.