A fixed-duration, measurable residual disease-guided approach in CLL: follow-up data from the phase 2 ICLL-07 FILO trial
Anne-Sophie Michallet, Rémi Letestu, Magali Le Garff-Tavernier, Carmen Aanei, Michel Ticchioni, Marie-Sarah Dilhuydy, Fabien Subtil, Valerie Rouille, Beatrice Mahe, Kamel Laribi, Bruno Villemagne, Gilles Salles, Olivier Tournilhac, Alain Delmer, Christelle Portois, Brigitte Pegourie, Veronique Leblond, Cecile Tomowiak, Sophie De Guibert, Frederique Orsini Piocelle, Anne Banos, Philippe Carassou, Guillaume Cartron, Luc-Matthieu Fornecker, Loic Ysebaert, Caroline Dartigeas, Malgorzata Truchan-Graczyk, Jean-Pierre Vilque, Thérèse Aurran, Florence Cymbalista, Stéphane Lepretre, Vincent Levy, Florence Nguyen-Khac, Pierre Feugier, Anne-Sophie Michallet, Rémi Letestu, Magali Le Garff-Tavernier, Carmen Aanei, Michel Ticchioni, Marie-Sarah Dilhuydy, Fabien Subtil, Valerie Rouille, Beatrice Mahe, Kamel Laribi, Bruno Villemagne, Gilles Salles, Olivier Tournilhac, Alain Delmer, Christelle Portois, Brigitte Pegourie, Veronique Leblond, Cecile Tomowiak, Sophie De Guibert, Frederique Orsini Piocelle, Anne Banos, Philippe Carassou, Guillaume Cartron, Luc-Matthieu Fornecker, Loic Ysebaert, Caroline Dartigeas, Malgorzata Truchan-Graczyk, Jean-Pierre Vilque, Thérèse Aurran, Florence Cymbalista, Stéphane Lepretre, Vincent Levy, Florence Nguyen-Khac, Pierre Feugier
Abstract
Trials assessing first-line, fixed-duration approaches in chronic lymphocytic leukemia (CLL) are yielding promising activity, but few long-term data are available. We report follow-up data from a phase 2 trial (ICLL07 FILO) in previously untreated, medically fit patients (N = 135). Patients underwent obinutuzumab-ibrutinib induction for 9 months; then, following evaluation (N = 130 evaluable), those in complete remission and with bone marrow measurable residual disease (BM MRD) <0.01% (n = 10) received ibrutinib for 6 additional months; those in partial remission and/or with BM MRD ≥0.01%, the majority (n = 120), also received 4 cycles of immunochemotherapy (fludarabine/cyclophosphamide-obinutuzumab). Beyond end of treatment, responses were assessed every 3 month and peripheral blood MRD every 6 months. At median follow-up 36.7 months from treatment start, progression-free and overall survival rates (95% confidence interval) at 3 years were 95.7% (92.0% to 99.5%) and 98% (95.1% to 100%), respectively. Peripheral blood MRD <0.01% rates were 97%, 96%, 90%, 84%, and 89% at months 16, 22, 28, 34, and 40, respectively. No new treatment-related or serious adverse event occurred beyond end of treatment. Thus, in previously untreated, medically fit patients with CLL, a fixed-duration (15 months), MRD-guided approach achieved high survival rates, a persistent MRD benefit beyond the end of treatment, and low long-term toxicity. This trial was registered at www.clinicaltrials.gov as #NCT02666898.
© 2021 by The American Society of Hematology.
Source: PubMed