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Ibrutinib demonstrates continued effectiveness in Waldenström’s Macroglobulinemia

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The latest results from a Phase II prospective, multicenter study published recently in The New England Journal of Medicine indicate that ibrutinib – a newly US-FDA approved drug  for Waldenström’s macroglobulinemia – continued to control the disease, with 95% of patients surviving for 2 years.

The trial, conducted by researchers at the Dana-Farber Cancer Institute (MA, USA) included 63 patients diagnosed with Waldenström’s macroglobulinemia who had received at least one previous treatment for the disease. In this trial, patients were administered daily ibrutinib orally, until the disease progressed or unacceptable adverse events presented.

This particular type of malignant B-cell lymphoma is caused by an abnormality in B lymphocytes in the bone marrow, which causes them to overproduce an immunoglobulin protein termed IgM that thickens the blood. Ibrutinib targets the cancer cells by inhibiting a pathway involving the Bruton’s tyrosine kinase protein, with response rate in this trial being measured in reduction in blood levels of IgM.

The results of this trial demonstrated that after receiving ibrutinib, median blood levels of IgM decreased from 3520 mg per deciliter to 880 mg per deciliter. Bone marrow involvement also decreased from 60 to 25%, and median hemoglobin levels increased from 10.5 g per deciliter to 13.8 g per deciliter.

The median overall response rate was 91% after a median of 19 months of treatment. The study also reported that in 69% of patients, the cancer had not progressed 2 years after treatment was started. In cases where the cancer did progress, it began at a median time of 9.6 months after commencing treatment.

A previous discovery from the same laboratory at the Dana-Farber Cancer Institute demonstrated that Waldenström’s macroglobulinemia is driven by genetic mutations termed MYD88 and CXCR4.  In this study, the researchers also assessed the influence of these two mutations on therapy responses and discovered that the drugs’ performance varied depending on which mutations – if any – were detected in the patients’ cancer cells.

The response rates were reported to be highest among patients who had the MYD88 but no CXCR4 mutations, followed by instances where the cancers carried both mutations, and finally followed by individuals in whom neither mutation was present.

First author Steven Treon from Bing Center for Waldenström’s Macroglobulinemia at Dana-Farber Cancer Institute commented: “These findings herald a new era for the treatment of Waldenström’s macroglobulinemia, and show how genome sequencing can lead to the discovery of cancer mutations that can be specifically targeted by new therapies.”

Sources: Treon S P, Tripsas C K, Meid K et al. Ibrutinib in Previously Treated Waldenström’s Macroglobulinemia. NEJM. 372, 1430–1440 (2015); Dana-Farber Cancer Institute press release

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