Evolution of Tumor Subclones and T-Cell Dynamics Underlie Variable Ibrutinib Responses in Waldenström Macroglobulinemia

Overview

Waldenström macroglobulinemia (WM) is a rare B-cell lymphoma in which abnormal lymphoplasmacytic cells build up in the bone marrow and produce excess IgM antibody. Many patients are treated with ibrutinib, a BTK inhibitor that blocks a key survival pathway in these cancer cells. Although ibrutinib is often effective, responses vary widely: some patients achieve durable disease control, while others develop resistance or progress during treatment.

This study explored why those differences happen. Using a prospective phase 2 trial of ibrutinib in previously untreated WM, the investigators followed tumor and immune cells over time with single-cell multiomics, a technology that can measure genetic and transcriptional changes in individual cells. The work provides a detailed view of how tumor subclones evolve and how T cells change during therapy.