Waldenstrom’s drug shows sustained benefit at 2 years

Ibrutinib, a newly approved drug for Waldenstrom’s Macroglobulinemia, a rare form of lymphoma, continued to control the rare blood cancer, with 95% of patients surviving for 2 years, according to a new study, published in The New England Journal of Medicine.

Researchers from Dana-Farber Cancer Institute conducted a phase 2, prospective multicenter study in 63 previously treated Waldenstrom’s patients that examined the efficacy and safety of daily dosed ibrutinib at 420 mg/day. They took ibrutinib as an oral drug daily until the disease worsened or unacceptable toxic effects occurred.

The median overall response rate was 91% after a median of 19 months of treatment, and in 69% of patients the cancer had not worsened 2 years after beginning treatment. When the cancer did progress, it began at a median time of 9.6 months after the start of treatment

The study found that after receiving the drug, median blood levels of IgM decreased from 3,520 mg per deciliter to 880 mg per deciliter; median hemoglobin levels increased from 10.5 g per deciliter to 13.8 g per deciliter, and bone marrow involvement decreased from 60% to 25%.

An earlier analysis of data from this phase 2 multicenter study supported FDA’s approval in January of ibrutinib as the first and only treatment for Waldenstrom’s that affects about 1,500 people annually in the United States.

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Dr TreonThe disease stems from an abnormality in B lymphocytes in the bone marrow causing them to overproduce IgM, an immunoglobulin protein that thickens the blood; patients may experience bleeding, dizziness, headaches, weight loss, bruising and nerve damage. Waldenstrom’s is driven by genetic mutations known as MYD88 and CXCR4, both of which were discovered by the Treon laboratory, which also showed that the MYD88 mutation triggers the abnormal activity of Bruton’s tyrosine kinase. The drug’s performance was influenced by which mutations, if any, were detected in the patients’ cancer cells. The highest response rates were in patients who had the MYD88 but no CXCR4 mutations; next highest was when the cancers carried both MYD88 and CXCR4 mutations, followed by patients in whom neither mutation was present.

“Ibrutinib is highly active and produces durable responses in previously treated Waldenstrom’s patients,” said first author Steven Treon, MD, PhD, director of the Bing Center for Waldenstrom’s Macroglobulinemia at Dana-Farber. “MYD88 and CXCR4 mutation status impact responses, and progression-free survival.”

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Adverse events related to the treatment included low white blood cell and platelet counts, bleeding, and atrial fibrillation in patients who had a history of the arrhythmia.

The research was supported by Pharmacyclics and Janssen Pharmaceuticals and several foundations.

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