Two clinical studies published in the New England Journal of Medicine ( NEJM ) suggest that the novel agent Ibrutinib shows real potential as a safe, effective, targeted treatment for adults with chronic lymphocytic leukemia ( CLL ) and for patients with mantle cell lymphoma ( MCL ).

Results from the phase Ib/II trial showed an overall response rate ( complete and partial ) of 71%. At 26 months the estimated progression-free survival rate was 75 % and overall survival was 83%.

Chronic lymphocytic leukemia is the most common form of leukemia with an estimated 15,000 American diagnosed annually. It is a cancer of B cells, which are a major component of the immune system along with T cells.

Ibrutinib ( PCI-32765 ) is the first drug designed to target Bruton's tyrosine kinase, a protein essential for CLL-cell survival and proliferation. Ibrutinib kills malignant B cells but has little effect on healthy T cells, unlike other CLL therapies. This leaves an important arm of the immune system largely intact, enabling patients to remain healthier during treatment.

The trial involved 85 relapsed CLL patients ( median age, 66 ) who took Ibrutinib once daily. Fifty-one patients received a 420 mg dose and 34 patients received an 840 mg dose. Long-term therapy was associated with modest side effects such as diarrhea, fatigue, and infection that usually resolved with no treatment delay.
Results from this phase II trial showed an overall response rate of 68%, with 21% of patient achieving a complete response and 47% achieving a partial response. Estimated overall survival was 58% at 18 months.

Mantle cell lymphoma is a type of non-Hodgkin lymphoma, a malignancy that is expected to strike nearly 70,000 Americans in 2013. About 7% of those cases will be MCL, a cancer of white blood cells called B lymphocytes, or B cells. Currently, oncologists treat MCL using combination chemotherapy or intensive chemotherapy plus immunotherapy, followed by stem-cell transplantation.

The trial involved 111 patients with relapsed or refractory mantle cell lymphoma who took Ibrutinib. The trial was conducted at 18 sites. Participants had received one to five prior treatments, which could include the drug Bortezomib, an agent sometimes used to treat MCL. The estimated median response duration was 17.5 months and estimated median progression-free survival was 14 months.

Source: Ohio State University Medical Center, 2013

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