Ibrutinib Shows Rapid, Dramatic Responses in Patients with CLL

May 2013, Vol 4, No 4

Washington, DC—More than 50% of patients with difficult-to-treat chronic lymphocytic leukemia (CLL) had tumor shrinkage during 6 months of treatment with ibrutinib, results of a phase 2 clinical trial showed.

Treatment with ibrutinib—which is currently under review by the US Food and Drug Administration (FDA)—led to a 1-year progression-free survival rate of 94%. Ibrutinib, a Bruton’s tyrosine kinase inhibitor, reduced spleen volume and tumor spread to bone, reported Adrian Wiestner, MD, PhD, Investigator, Laboratory of Lymphoid Malignancies, National Institutes of Health, Bethesda, MD, at the American Association for Cancer Research (AACR) 2013 annual meeting.

Dramatic responses have occurred quickly in some patients.

“Some patients have had more than a 90% reduction in lymph node disease after 2 months,” said Dr Wiestner. Responses to ibrutinib appear to be durable, he added.

The drug demonstrated activity in patients whose tumors arise from the deletion of chromosome 17p (del[17p]), which is associated with poor response to conventional therapies and with poor prognosis.

Unlike other therapies for CLL, ibrutinib targets the enzyme that mediates B-cell signaling that is associated with disease progression. Ibrutinib is being evaluated as a single agent, whereas conventional CLL treatment typically consists of a combination of chemotherapy and immunotherapy.

Dr Wiestner reported findings from a study involving 54 patients with CLL, 29 of whom had the del(17p) and 25 patients who did not have del(17p). All patients received ibrutinib 420 mg daily for 6 months.

At the end of the treatment period, 95% of the patients had at least a 50% reduction in lymph node disease, the median absolute lymphocyte count declined by 62%, and all of the patients had a reduction in spleen volume. Among 26 patients who underwent bone marrow biopsy, tumor infiltration was reduced by 82%.

Of 44 patients evaluable for response, more than 50% met international criteria for partial response, and similar rates were seen in patients with del(17p) and in the 25 patients (aged ≥65 years) with no del(17p).

Ibrutinib was well tolerated, according to Dr Wiestner. The most frequent adverse events were grade 1 or 2 diarrhea, rash, arthralgia, cramps, stomatitis, and fatigue. Grade 3 adverse events occurred in 13% of the patients and consisted mostly of infections and rash. Two patients died of causes unrelated to treatment.

At the time of the AACR meeting, the FDA designated ibrutinib as an oncologic “breakthrough therapy,” for 2 B-cell malignancies—mantle-cell lymphoma and Waldenström’s macroglobulinemia. A breakthrough therapy designation is intended to expedite the development and review of therapies that have shown potential as improvements over existing treatments. A few weeks later, the FDA granted a third breakthrough designation for ibrutinib for the treatment of patients with chronic lymphocytic leukemia.

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