A fixed-duration, immunochemotherapy approach in CLL: 5.5-year results from the phase 2 ICLL-07 FILO trial.
Fiche publication
Date publication
avril 2023
Journal
Blood advances
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FEUGIER Pierre, Pr FORNECKER Luc-Matthieu
Tous les auteurs :
Michallet AS, Letestu R, Le Garff-Tavernier M, Campos L, Ticchioni M, Dilhuydy MS, Morisset S, Rouille V, Mahe B, Laribi K, Villemagne B, Ferrant EF, Tournilhac O, Delmer AJ, Molina L, Leblond V, Tomowiak C, De Guibert S, Orsini Piocelle F, Banos A, Carassou P, Cartron G, Fornecker LM, Ysebaert L, Dartigeas C, Truchan-Graczyk M, Vilque JP, Aurran Schleinitz T, Cymbalista F, Leprêtre S, Lévy V, Nguyen-Khac F, Feugier P
Lien Pubmed
Résumé
In previously untreated, medically fit patients with chronic lymphocytic leukemia, research is focused on developing fixed-duration strategies to improve long-term outcomes whilst sparing patients from serious toxicities. The ICLL-07 trial evaluated a fixed-duration (15-month) immunochemotherapy approach where, following 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 62.2% (84/135) of all patients enrolled achieved CR with BM MRD <0.01%. Here we report follow-up at median 63 months. PB MRD was assessed 6 monthly beyond 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 PB MRD status were apparent according 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.
Référence
Blood Adv. 2023 04 7;: