Ibrutinib is a safe and highly active treatment among previously untreated patients with Waldenstrom macroglobulinemia (WM), according to a poster being presented at the 2017 American Society of Hematology (ASH) Annual Meeting in Atlanta, Georgia.1
Ibrutinib — a Bruton’s tyrosine kinase (BTK) inhibitor — is currently used among patients with WM who have previously received treatment, but its efficacy as a first-line therapy among treatment-naive 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 65%. All patients had MYD88 mutation–positive disease, and 47% of patients had a CXCR4 mutation.
The median time on therapy was 8.1 months; the median time on therapy for patients with a CXCR4 wild-type or CXCR4 mutation was 9.4 months vs 8.0 months, respectively (P = .98). The overall response rate was 96.7%, the major response rate (greater than partial response) was 80%, and a very good partial response was reached by 17% of patients. No patients had a complete response.
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 [WM], and show that ibrutinib is highly active and well-tolerated as a single agent, with no unexpected toxicities.”
Read more of Cancer Therapy Advisor‘s coverage of the American Society of Hematology (ASH) 2017 meeting by visiting the conference page.