Is Ibrutinib, a New Weapon Against Lymphatic Cancer, More Effective Than Ofatumumab?

A comprehensive, reliable study published last month in the British medical journal compared ibrutinib with ofatumumab in chronic lymphocytic leukemia (CLL) after at least one unsuccessful treatment. Ibrutinib was more beneficial in terms of both response and survival.

Chronic lymphocytic leukemia (CLL) is a cancer of the blood and bone marrow arising from lymphocytes, a subtype of white blood cells that defend the body, and is the most common chronic leukemia. Small lymphocytic lymphoma (SLL) also arises from lymphocytes and is very similar to CLL. The only difference is that SLL involves the blood less extensively. If large numbers of tumor cells are not circulating, it is called SLL; if they are, it is called CLL. The two are therefore considered almost the same disease and treated with the same strategies. Options include watchful waiting, chemotherapy, radiotherapy, surgery such as spleen removal, and stem cell transplantation (bone marrow transplantation). However, because treatment is difficult and a definitive cure is often not achieved, particularly in relapsed or resistant CLL/SLL, alternative approaches are being investigated. Recently, much attention has focused on targeted treatments, particularly monoclonal antibodies. These drugs are designed to bind to and destroy leukemia cells without harming normal cells. Ofatumumab, approved in 2009, is one such treatment.

Ibrutinib, meanwhile, is a once-daily oral capsule and a targeted treatment that blocks a protein controlling the growth and spread of lymphatic cancer. It is not a newly discovered drug. It blocks a protein in the signaling pathways of B lymphocytes (Bruton thyrosine kinase), which give rise to 80-85% of lymphomas. Although the FDA (Food and Drug Administration) initially approved ibrutinib only for mantle cell lymphoma in November 2013, approvals for other lymphoma types were expected to follow. Approval for CLL/SLL in February 2014 justified that expectation. Studies then began comparing ibrutinib with existing treatments, including the recently published comparison with ofatumumab.

In this study, 391 patients with relapsed or resistant CLL/SLL who had received at least one unsuccessful treatment were divided into 2 groups. One received ibrutinib regularly each day and the other ofatumumab, with approximately 10 months of follow-up. Analysis showed a 12-month survival rate of 90% with ibrutinib and 81% with ofatumumab. Response rates were also substantially higher with ibrutinib (42% versus 4%). No major differences in side effects were observed.

In conclusion, ibrutinib appears considerably superior to ofatumumab in both response and survival in chronic lymphocytic leukemia (CLL) after at least one unsuccessful treatment. This is encouraging for patients with CLL/SLL and other lymphatic cancers, since ibrutinib is expected to gain approval for additional types in the near future. Nevertheless, as we always emphasize, caution is advisable, and every new development should not immediately be put into clinical practice.