Ibrutinib monotherapy resulted in sustained responses and a meaningful progression-free survival benefit among heavily pretreated patients with rituximab-refractory Waldenström macroglobulinemia, according to a study presented at the American Society of Hematology (ASH) 58th Annual Meeting and Exposition (also published in The Lancet Oncology.)1

Few treatment options exist for rituximab-refractory Waldenström macroglobulinemia. Researchers evaluated the efficacy and safety of ibrutinib in this patient setting.

For the substudy of an international, phase 3 trial (ClinicalTrials.gov Identifier: NCT02165397), researchers enrolled 31 patients with Waldenström macroglobulinemia whose disease relapsed less than 12 months since the last dose of rituximab or who failed to achieve at least a minor response to rituximab therapy. All participants received ibrutinib daily until disease progression or unacceptable toxicity.

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After a median follow-up of 18.1 months, 90% of patients achieved an overall response, including 71% who had a major response.

The 18-month progression-free survival and overall survival rates were 86% (95% CI, 66-94) and 97% (95% CI, 79-100), respectively.

Investigators observed a median increase in hemoglobin levels of 1.1 g/dL after 4 weeks of ibrutinib therapy. The median hemoglobin level at week 49 was 12.7 g/dL.

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The most frequently reported grade 3 or higher adverse events were neutropenia (13%), hypertension (10%), and anemia, thrombocytopenia, and diarrhea each in 6%. Nearly one-third of patients reported serious adverse events.

The findings suggest that single-agent ibrutinib is a new chemotherapy-free treatment strategy for heavily pretreated, rituximab-refractory Waldenström macroglobulinemia.


  1. Dimopoulos MA, Trotman J, Tedeschi A, et al. Ibrutinib for patients with rituximab-refractory Waldenström’s macroglobulinaemia (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial. Lancet Oncol. 2016 Dec 9. doi: 10.1016/S1470-2045(16)30632-5 [Epub ahead of print]