Ibrutinib plus fludarabine, cyclophosphamide, and rituximab as initial treatment for younger patients with chronic lymphocytic leukaemia: a single-arm, multicentre, phase 2 trial

Publication date: Available online 14 June 2019Source: The Lancet HaematologyAuthor(s): Matthew S Davids, Danielle M Brander, Haesook T Kim, Svitlana Tyekucheva, Jad Bsat, Alexandra Savell, Jeffrey M Hellman, Josie Bazemore, Karen Francoeur, Alvaro Alencar, Leyla Shune, Mohammad Omaira, Caron A Jacobson, Philippe Armand, Samuel Ng, Jennifer Crombie, Ann S LaCasce, Jon Arnason, Ephraim P Hochberg, Ronald W TakvorianSummaryBackgroundFludarabine, cyclophosphamide, and rituximab (FCR) can improve disease-free survival for younger (age ≤65 years) fit patients with chronic lymphocytic leukaemia with mutated IGHV. However, patients with unmutated IGHV rarely have durable responses. Ibrutinib is active for patients with chronic lymphocytic leukaemia irrespective of IGHV mutation status but requires continuous treatment. We postulated that time-limited ibrutinib plus FCR would induce durable responses in younger fit patients with chronic lymphocytic leukaemia.MethodsWe did a multicentre, open-label, non-randomised, single-arm phase 2 trial at seven sites in the USA. We enrolled patients aged 65 years or younger with previously untreated chronic lymphocytic leukaemia. Our initial cohort (original cohort) was not restricted by prognostic marker status and included patients who had del(17p) or TP53 aberrations. After a protocol amendment (on March 21, 2017), we enrolled an additional cohort (expansion cohort) that included patients without del(17p). Ibrutinib was given orally (420 mg/d...
Source: The Lancet Haematology - Category: Hematology Source Type: research