Overcoming ibrutinib resistance

Imbruvica ibrutinib's unprecedented response rate in mantle cell lymphoma is generating excitement around the new drug, but as with many targeted cancer therapies, tumors can ultimately become resistant. A recent study from Weill Cornell Medical College suggests that another therapeutic about to hit the market-the cyclin dependent kinase 4 inhibitor palbociclib-could prevent or overcome resistance when used in combination with Imbruvica or a phosphoinositide 3-kinase inhibitor.1

The researchers are now beginning clinical trials to test the different combinations in patients resistant to Imbruvica.

Mantle cell lymphoma (MCL) is a form of non-Hodgkin's lymphoma (NHL) that is highly proliferative and thus particularly prone to drug resistance. Imbruvica received accelerated approval from the FDA last year for recurrent MCL and has grabbed attention from physicians and investors alike for the unusually long response period it provides before the disease recurs.

Imbruvica is marketed by Pharmacyclics Inc. and Johnson & Johnson for recurrent MCL and chronic lymphocytic leukemia (CLL). It is also in Phase III trials for B cell lymphoma and NHL and Phase II testing for other lymphomas and multiple myeloma.

About one-third of patients show primary resistance to the drug, which means they do not respond when it is first added to their treatment regimen. In addition, many patients who initially respond stop doing so after taking the drug for a period of time-termed acquired resistance.

Mark Roschewski, staff clinician in the Lymphoma Therapeutics Section of the NIH's Center for Cancer

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