CLL Coverage from Every Angle

ASH 2021: Updated Phase III FLAIR Results of Ibrutinib Plus Rituximab in Previously Untreated CLL

By: Vanessa A. Carter, BS
Posted: Friday, December 17, 2021

The ongoing, phase III FLAIR trial analyzed clinical outcomes of rituximab plus ibrutinib or fludarabine and cyclophosphamide in patients with previously untreated chronic lymphocytic leukemia (CLL). During the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 642), Peter Hillmen, MBChB, PhD, of St James’s University Hospital, Leeds, United Kingdom, and colleagues concluded that the ibrutinib combination demonstrated a “superior” progression-free survival over fludarabine and cyclophosphamide, although there was no apparent difference in overall survival.

This multicenter trial enrolled 771 patients with CLL who were previously untreated. Participants were randomly assigned 1: 1 to receive either six cycles of fludarabine and cyclophosphamide plus rituximab every 28 days (n = 385) or ibrutinib plus rituximab for up to 6 years (n = 386).

At the median follow-up of 52.7 months, the median progression-free survival of the ibrutinib combination was not reached, although it was superior to the 67-month survival of the fludarabine and cyclophosphamide combination (P < .001). Additionally, the progression-free survival improved among patients with IGHV-unmutated CLL (P < .001) but not for those with mutations (P = .179). There was no apparent difference in overall survival between both arms.

Compared with the FLAIR trial results from 2009 to 2012, the 4-year overall survival for patients on fludarabine, cyclophosphamide, and rituximab appeared to improve (94.5% vs. 84.2%). Rates of serious adverse events were similar among both groups (53.7% vs. 53.4%), although more individuals treated with fludarabine and cyclophosphamide experienced infections (33.6% vs. 27.1%) and blood/lymphatic events (19.8% vs. 10.7%) than those treated with ibrutinib. Individuals given ibrutinib experienced cardiac events more frequently (8.1% vs. 1.1%), and eight experienced sudden or cardiac death; two patients given fludarabine and cyclophosphamide experienced sudden or cardiac death.

Disclosure: For full disclosures of the study authors, visit

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