Second-Line Ibrutinib for Waldenström Macroglobulinemia

Waldenström macroglobulinemia (WM; lymphoplasmacytic lymphoma) is characterized by the presence of an elevated immunoglobulin M (IgM) paraprotein, hyperviscosity syndrome, anemia, and peripheral neuropathy. Current treatment is focused on cytotoxic chemotherapy and/or anti-CD20 immunotherapy. To assess the activity of the B-cell receptor–inhibitor ibrutinib in WM, investigators conducted an industry-sponsored, prospective, single-agent, multicenter study of patients who had received ≥1 prior therapy.

A total of 63 symptomatic WM patients, with a median of two prior therapies (range, 1–9), received ibrutinib (420 mg daily). Clinical responses were correlated with the presence of mutations in the MYD88 and CXCR4 genes, one or both of which are present in virtually all WM cases.

The overall response rate (ORR; the primary objective) was 90%; ORR was highest in patients with MYD88 mutation (100%) and in those with mutation in both genes (86%). Rates of 2-year overall survival and progression-free survival were 95% and 69%, respectively. Most patients had a decrease in serum IgM level, and most had improvement in bone-marrow involvement with a concomitant increase in hemoglobin levels. Toxicity included grade 3 or higher neutropenia in 13% of patients and thrombocytopenia in 14%, with grade 2 or higher bleeding in 6% of patients. Atrial fibrillation, a known risk with ibrutinib therapy, occurred in 5% of patients who had a history of the disorder. No patient developed a flare in IgM level, which otherwise commonly occurs during initial rituximab therapy.