The Food and Drug Administration (FDA) has approved Imbruvica (ibrutinib; Janssen) in combination with rituximab for the treatment of Waldenström’s macroglobulinemia.

Imbruvica, a Bruton tyrosine kinase inhibitor, was originally approved as monotherapy for Waldenström’s macroglobulinemia in January 2015. This expanded approval was based on results from the iNNOVATE study, a double-blind, placebo-controlled trial evaluating Imbruvica in combination with rituximab vs placebo + rituximab in 150 patients with either relapsed/refractory disease or previously untreated Waldenström’s macroglobulinemia. The major efficacy outcome measure of the study was progression-free survival (PFS) assessed by an Independent Review Committee (IRC).

Results showed that at 30 months, the combination of Imbruvica + rituximab was associated with a significant improvement in PFS compared with placebo + rituximab (82% vs 28%, respectively). Patients treated with Imbruvica + rituximab experienced an 80% reduction in relative risk of disease progression or death compared with those treated with placebo + rituximab (hazard ratio 0.20; <.001). In addition, the rate of response, a key secondary endpoint, was greater in the Imbruvica + rituximab group compared with placebo + rituximab (72% vs 32%, respectively; <.001).

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With regard to safety, the most common adverse events associated with combination therapy included bruising, musculoskeletal pain, hemorrhage, diarrhea, rash, arthralgia, nausea, and hypertension.

“Based on these results, Imbruvica in combination with rituximab may be considered as a first- and second-line option for appropriate people diagnosed and living with [Waldenström’s macroglobulinemia],” said Meletios A. Dimopoulos, MD, Professor and Chairman of the Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece, and iNNOVATE lead study investigator.

The updated prescribing information for Imbruvica states that when administering Imbruvica in combination with rituximab, clinicians should consider administering Imbruvica prior to rituximab when given on the same day.

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