Ibrutinib Boosts CLL Overall, Progression-Free Survival

Ibrutinib phase III trial results challenge chlorambucil as first-line treatment for chronic lymphocytic leukaemia

medwireNews: Ibrutinib is superior to chlorambucil for the first-line treatment of chronic lymphocytic leukaemia (CLL) and small lymphocytic leukaemia, suggest RESONATE-2 trial results.

The primary endpoint of progression-free survival was significantly longer with the Bruton’s tyrosine kinase inhibitor than with the gold-standard chemotherapy agent, with an unreached median value versus a median of 18.9 months, and a hazard ratio (HR) for the risk of progression or death of 0.16.

The 136 ibrutinib-treated patients also had significantly longer overall survival than the 133 patients given chlorambucil, with an estimated 2-year rate of 98% versus 85%, and a HR for death of 0.16, the researchers report in The New England Journal of Medicine.

The overall response rate was significantly higher for ibrutinib than chlorambucil, at 86% versus 35%.

And ibrutinib was associated with significantly higher rates of “sustained increases” from baseline in both haemoglobin and platelet levels than the chemotherapy agent.

“This finding has particular clinical relevance because bone marrow failure is a common cause of complications in patients with CLL, with anemia and thrombocytopenia being frequent indications for initiating treatment in this population”, observe Jan Burger, from the University of Texas MD Anderson Cancer Center in Houston, USA, and co-workers.

They continue: “[I]n this older population of patients with CLL, many of whom had coexisting conditions, oral ibrutinib was administered continuously with a safety profile consistent with that in prior reports, which permitted the vast majority of patients to continue taking treatment at the completion of the study.”

Specifically, ibrutinib treatment lasted for a median of 17.4 months versus 7.1 months for chlorambucil, with discontinuation because of adverse events reported in 9% and 23%, respectively.

In all, 42% of ibrutinib-treated patients experienced diarrhoea, with grade 3 symptoms in 4%, and at least 20% reported fatigue, cough and nausea. At least 20% of chlorambucil-treated patients experienced nausea, vomiting, fatigue, neutropenia and anaemia; all these adverse events were more common with chlorambucil than ibrutinib.

The authors observe that the magnitude of improvement in overall survival with ibrutinib versus chlorambucil is greater than previously reported in studies comparing the use of chlorambucil alone versus alongside an anti-CD20 agent.

Noting that these trials included patients who had already progressed on chlorambucil, they hypothesise that treatment naive-patients may have less CLL- or treatment-related mortality.

“These findings suggest that better results with ibrutinib might be obtained when it is used as first-line treatment rather than for later relapses or in patients with refractory disease”, Jan Burger et al suggest.


Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med 2015; Advance online publication 6 December. DOI: 10.1056/NEJMoa1509388

medwireNews (www.medwireNews.com ) is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2015