Ibrutinib is a safe and highly active treatment among previously untreated patients with Waldenström’s macroglobulinemia (WM), according to a poster to be presented at the 2017 American Society of Hematology (ASH) Annual Meeting.

Ibrutinib — a Bruton tyrosine kinase (BTK) inhibitor — is currently used to treat patients with WM who have previously received treatment, but its efficacy as a first-line therapy in treatment-naïve patients is unknown.

For this prospective phase 2 study (ClinicalTrials.gov Identifier: NCT02604511), researchers enrolled 30 patients with untreated WM and administered ibrutinib 420 mg daily. Patients’ baseline characteristics included median serum IgM of 4369, and median bone marrow disease involvement was 65%. All patients had MYD88 mutation-positive disease, and 47% of patients had the CXCR4 mutation.

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Median time on therapy was 8.1 months; median time on therapy for patients with CXCR4 wild-type and CXCR4 mutation was 9.4 months compared with 8.0 months, respectively (P = .98). The overall response rate was 96.7%, major response rate (greater than partial response) was 80%, and very good partial response (VGPR) was achieved by 17% of patients. No patients achieved complete response.

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Median serum IgM levels decreased from 4380 to 1786 (P =.0001) at best response; at baseline, 60% of patients had a serum IgM greater than 3000 mg/dL compared with just 7% of patients at best response (P <.0001). At best response, median bone marrow involvement was reduced to 20% from 65% (P <.0001), and 70% and 80% of patients with adenopathy and splenomegaly, respectively, had a reduction or resolution of these conditions. Patients also had an increase in median hemoglobin levels, from 10.3 to 13.6 g/dL (P <.0001).

Mutated CXCR4 was associated with delayed patient response to ibrutinib.

The authors concluded that “[o]ur findings provide the first report of activity and safety of ibrutinib in previously untreated and symptomatic patients with Waldenström’s macroglobulinemia, and show that ibrutinib is highly active and well-tolerated as a single agent, with no unexpected toxicities.”


Treon SP, Gustine J, Meid K, et al. Ibrutinib is highly active as first line therapy in symptomatic Waldenstrom’s macroglobulinemia. Oral presentation at: American Society of Hematology 59th Annual Meeting & Exposition; December 9-12, 2017; Atlanta, GA.