Ibrutinib, a Bruton's
kinase inhibitor, was granted an accelerated approval by the US Food and Drug Administration in November, 2013, for the treatment of relapsed or refractory
mantle cell lymphoma and subsequently for the treatment of relapsed refractory
chronic lymphocytic leukemia in February, 2014. In the pivotal phase 2 study of 111 patients with relapsed or refractory
mantle cell lymphoma, the overall response rate in patients who received
ibrutinib 560 mg daily was 68%. The median progression-free survival was 13.9 months, and the overall survival was 58% at 18 months. In a recently published phase 3 trial (RESONATE) that compared
ibrutinib and
ofatumumab for the treatment of relapsed and refractory
chronic lymphocytic leukemia or
small lymphocytic lymphoma,
ibrutinib at the daily dosage of 420 mg demonstrated a significantly higher overall response rate (43% in
ibrutinib vs. 4% in
ofatumumab) and a significantly improved overall survival at 12 months (90%
ibrutinib vs. 81%
ofatumumab). Similar clinical benefits were shown regardless of del (17 p).
Ibrutinib was well tolerated, and dose-limiting toxicity was not observed.
Ibrutinib has shown durable remission, improved progression-free survival and overall survival, and favorable safety profile in indolent B-cell lymphoid
malignancies.
Ibrutinib, as a monotherapy, is an effective treatment modality as a
salvage therapy for treatment of
mantle cell lymphoma and
chronic lymphocytic leukemia /
small lymphocytic lymphoma, particularly in older patients (age ≥70 years) who are not a candidate for intensive
chemotherapy and/or those with del (17 p). In patients with
chronic lymphocytic leukemia and del (17 p), the current practice guideline recommends
ibrutinib as an upfront treatment option. Current on-going trials will further define its role as upfront
therapy and/or as a combination
therapy in indolent B-cell lymphoid
malignancies.