Ibrutinib is a highly active and tolerable therapy for symptomatic, relapsed, or refractory patients with Waldenström macroglobulinemia (WM) and a preferable option for use in previously treated patients, according to a study published in the Journal of Clinical Oncology (2020;JCO2000555. doi:10.1200/JCO.20.00555).

The study aimed to determine whether ibrutinib produced long-term responses in previously treated WM and if MYD88 and CXCR4 mutations impacted clinical outcomes.

A total of 63 previously treated patients with WM received ibrutinib at a dose of 420 mg daily. Of these patients, 40% were refractory to their previous therapy. Statistical tests analyzed response rates, survival curve estimates, and for genomic comparisons.

“The primary objective was to determine the overall and major response rates using modified criteria from the 6th International Workshop on WM as before,” wrote Steven Treon, MD, PhD, Bing Center for Waldenström’s Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts, and colleagues.

“Secondary objectives included determination of progression-free survival (PFS) and drug safety,” they continued.

The median follow-up was 59 months and the overall response rate was 90.5% and the major response rate was 79.4%. After ibrutinib, medical serum IgM levels declined from 3,520 to 821 mg/dL, bone marrow disease involvement declined from 60% to 20%, and hemoglobin rose from 10.3 to 14.2 g/dL (P < .001 for all comparisons).

The study authors reported that responses were impacted by MYD88 and CXCR4 status. Patients with MYD88Mut, wild-type (WT) CXCR4 showed higher major (97.2% versus 68.2%; P <.0001) and very good partial (47.2% versus 9.1%; P <.01) response rates and a shorter time to major response (1.8 versus 4.7 months; P = .02) versus patients with MYD88Mut CXCR4Mut. Conversely, 4 patients who had MYD88WT disease showed no major responses.

No unexpected toxicities were experienced in the patients tested. Atrial fibrillation increased to 12.7% but most of these patients continued therapy.

“Compared with other available therapies, the efficacy and long-term safety of ibrutinib make ibrutinib a preferable option for use in previously treated WM,” concluded Dr Treon and colleagues. —Lisa Kuhns