A fixed-duration immunochemotherapy approach in CLL: 5.5-year results from the phase 2 ICLL-07 FILO trial
Anne‐Sophie Michallet, Rémi Letestu, Magali Le Garff‐Tavernier, Lydia Campos, Michel Ticchioni, Marie‐Sarah Dilhuydy, Stéphane Morisset, Valérie Rouille, Béatrice Mahé, Kamel Laribi, Bruno Villemagne, Emmanuelle Ferrant, Olivier Tournilhac, Alain Delmer, Lysiane Molina, Véronique Leblond, Cécile Tomowiak, Sophie de Guibert, Frédérique Orsini-Piocelle, Anne Banos, P. Carassou, Guillaume Cartron, Luc Mathieu Fornecker, Loïc Ysebaert, Caroline Dartigeas, Margot Truchan-Graczyk, Jean‐Pierre Vilque, Thérèse Aurran Schleinitz, Florence Cymbalista, Stéphane Leprêtre, Vincent Lévy, Florence Nguyen‐Khac, Pierre Feugier
Abstract
In previously untreated, medically fit patients with chronic lymphocytic leukemia (CLL), research is focused on developing fixed-duration strategies to improve long-term outcomes while sparing patients from serious toxicities. The ICLL-07 trial evaluated a fixed-duration (15-month) immunochemotherapy approach in which after obinutuzumab-ibrutinib induction for 9 months, patients (n = 10) in complete remission (CR) with bone marrow (BM) measurable residual disease (MRD) <0.01% continued only ibrutinib 420 mg/day for 6 additional months (I arm), whereas the majority (n = 115) received up to 4 cycles of fludarabine/cyclophosphamide-obinutuzumab 1000 mg alongside the ibrutinib (I-FCG arm). Primary analysis at month 16 showed that 84 of 135 (62.2%) patients enrolled achieved CR with a BM MRD <0.01%. Here, we report follow-up at median 63 months. Peripheral blood (PB) MRD was assessed 6 monthly beyond the end of treatment using a highly sensitive (10-6) flow cytometry technique. In the I-FCG arm, the PB MRD <0.01% rate (low-level positive <0.01% or undetectable with limit of detection ≤10-4) in evaluable patients was still 92.5% (74/80) at month 40 and 80.6% (50/62) at month 64. No differences in the PB MRD status were apparent per to the IGHV mutational status. In the overall population, 4-year progression-free and overall survival rates were 95.5% and 96.2%, respectively. Twelve deaths occurred overall. Fourteen serious adverse events occurred beyond the end of treatment. Thus, our fixed-duration immunochemotherapy approach produced deep and sustained PB MRD responses, high survival rates, and low long-term toxicity. A randomized trial is needed to compare our immunochemotherapy approach with a chemotherapy-free strategy. This trial was registered at www.clinicaltrials.gov as #NCT02666898.