Ibrutinib plus rituximab for the treatment of adult patients with Waldenström's macroglobulinemia: a safety evaluation.

: Waldenström's macroglobulinemia (WM), an orphan disease, is a rare low-grade B-cell lymphoplasmacytic lymphoma with unique clinical features and monoclonal IgM production. Rituximab remains to this date the backbone of most commonly used treatment combinations. The FDA/EMA approval of Ibrutinib, the first-in-class BTK inhibitor, either as monotherapy or in combination with rituximab, changed the treatment landscape of the disease.: Clinical trial data that demonstrate mode of action, efficacy, and the safety profile of each agent will be covered. A safety analysis of the combination treatment will also be performed to point out its high efficacy and overall favorable toxicity profile. The disadvantages and treatment gaps that still exist in the treatment of WM which relate to the need for long-term ibrutinib administration and the lack of deep remissions and subsequent disease relapse, will also be reviewed.: The ibrutinib-rituximab combination is both effective and safe, in the newly-diagnosed and relapsed-refractory disease setting. The optimal therapeutic approach for WM patients remains however to be established. The question of which combinatory (or synergistic) regimen can allow for a fixed-treatment duration, deep and durable responses with a safe toxicity profile is being addressed in ongoing clinical trials.