Maintenance therapy in CLL: resolving the controversy

Abstract

The standard of care for chronic lymphocytic leukaemia is fast changing. For younger patients, frontline chemoimmunotherapy with regimens such as fludarabine, cyclophosphamide, and rituximab 1 Thompson PA Tam CS O'Brien SM et al. Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia. Blood. 2016; 127: 303-309 Crossref PubMed Scopus (381) Google Scholar , 2 Hallek M Fischer K Fingerle-Rowson G et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010; 376: 1164-1174 Summary Full Text Full Text PDF PubMed Scopus (1545) Google Scholar are still appropriate standard-of-care, whereas kinase inhibitors such as ibrutinib are commonly used in older patients, and in those with relapsed disease. 3 Byrd JC Furman RR Coutre SE et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013; 369: 32-42 Crossref PubMed Scopus (1742) Google Scholar Attempts to intensify the regimen of fludarabine, cyclophosphamide, and rituximab with addition of drugs such as mitoxantrone 4 Faderl S Wierda W O'Brien S Ferrajoli A Lerner S Keating MJ Fludarabine, cyclophosphamide, mitoxantrone plus rituximab (FCM-R) in frontline CLL <70 years. Leuk Res. 2010; 34: 284-288 Summary Full Text Full Text PDF PubMed Scopus (39) Google Scholar resulted in additional toxicity and no improvement in therapeutic efficacy. Thus, current efforts are directed towards the use of less toxic drugs such as monoclonal antibodies and lenalidomide as post-induction therapy, commonly referred to as maintenance therapy. Rituximab maintenance versus observation alone in patients with chronic lymphocytic leukaemia who respond to first-line or second-line rituximab-containing chemoimmunotherapy: final results of the AGMT CLL-8a Mabtenance randomised trialRituximab maintenance therapy prolongs progression-free survival in patients achieving at least a PR to induction with rituximab plus chemotherapy, and the treatment is well tolerated overall. Although it is associated with an increase in infections, there is no excess in infection mortality, suggesting that remission maintenance with rituximab is an effective and safe option in the management of chronic lymphocytic leukaemia in early treatment phases. Full-Text PDF