Chronic Lymphocytic Leukemia

The upcoming issue of The Medical Letter (April 14, 2014) includes an article on a promising new drug for chronic lymphocytic leukemia (CLL), which is the most common type of leukemia seen in the West. One of the reasons it is so common is that many patients with CLL live for decades, and did so even before any treatment was available. Some remain asymptomatic without any treatment. Less fortunate patients may die in a matter of months, even now that we have a whole arsenal of treatment possibilities.

The standard treatment for CLL has been a combination of 2 cytotoxic agents, cyclophosphamide and fludarabine, with the monoclonal antibody rituximab, which binds to the CD-20 antigen found on the surface of most normal and malignant B-cells and lyses them. No specific genetic abnormality has been identified as the trigger for CLL, but B-cell receptor signaling drives the proliferation and continued survival of the malignant cells. Two other anti-CD20 antibodies and 2 alkylating agents have been added to the CLL armamentarium in recent years, and all of these have improved outcomes to some degree, but over time patients with more aggressive disease generally relapse, and some go on to allotransplantation. One additional problem in CLL is that most of the patients are over 70, and many have coexisting morbidities that make it difficult to tolerate any of these treatments.

So here comes ibrutinib (Imbruvica), which inhibits a kinase that is required for B-cell signaling, with some positive results, even in some patients with a notoriously unfavorable biomarker (17p13.1 deletion). One peculiar feature of the response to ibrutinib has been an initial lymphocytosis, which does not represent progression of the disease, but rather a mobilization of leukemic B-cells from lymph nodes and other sites into the blood. The data are still limited, both in the number of patients treated and in the regimens that have been tried (only monotherapy trials have been published to date), but at least some experts are excited about them. You can find the details in the next issue of The Medical Letter.

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