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Resources for Hematology Fellows

Spotlight on Therapeutics: Ibrutinib

It is an exciting time to be a hematology fellow. Currently, there is an unprecedented influx of new therapeutics emerging from clinical trials that stand in sharp contrast to standard chemotherapy. They are oral-targeted small molecules and have a favorable side-effect profile. One of the most exciting new drugs is ibrutinib, an oral irreversible Bruton’s tyrosine inhibitor. In early clinical trials, ibrutinib has been shown to be highly active in the relapse and refractory setting of both mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) as recently reported in two separate studies in the New England Journal of Medicine.1,2 A phase II study looked at patients with MCL who had a median of three prior therapies. Patients were enrolled into two groups, those who had previously received bortezomib and those who had not. An overall response rate (RR) of 68 percent was seen (including a 21% complete response rate) with single-agent ibrutinib. Prior bortezomib therapy had no effects on outcomes. In CLL, a phase Ib-II study examined patients with relapsed and refractory disease with a reported RR of 71 percent. This was irrespective of clinical and genomic risk factors, including patients with the deleterious 17p13.1 deletion. One could speculate that with new agents like ibrutinib, the prognostic value of genetic mutations in CLL may be marginalized by its efficacy.

These two studies make ibrutinib one of the most promising agents in the most difficult-to-treat lymphomas, even in heavily pre-treated patients. Currently, phase III trials are underway evaluating ibrutinib in the frontline setting and in combination with bendamustine and rituxan for patients with MCL and CLL. In mid-July, the drug manufacturer applied for FDA approval via the new Breakthrough Therapy Designation pathway, and approval is expected within the coming months.


  1. 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
  2. Wang ML, Rule S, Martin P, et al Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med 2013;369:507-516