Ibrutinib As a Promising Treatment for Heavily Pretreated Waldenström Macroglobulinemia: A Real World Data

Background:Waldenström Macroglobulinemia (WM) remains an incurable disease with a heterogeneous course, relapse following initial treatment happens in virtually all patients. Ibrutinib, a Bruton Tyrosine Kinase inhibitor, is a promising drug used in WM, chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone lymphoma, and chronic graft versus host disease. Ibrutinib first received FDA approval in WM as a monotherapy in January 2015 and expanded the approved use of ibrutinib with rituximab in August 2018.Ibrutinib-related prior data in Waldenström Macroglobulinemia (WM) remain sparse, particularly outside of clinical trials. Herein, we share a real-life experience using off-label ibrutinib in the treatment of heavily pretreated WM.

Methods:This multicenter retrospective study conducted in eight different sites included 13 adult patients diagnosed with WM and used off-label ibrutinib monotherapy or with rituximab from April 2016 to November 2019. Disease-refractoriness to prior therapy was defined as progression on therapy or within 2 months of treatment interruption. The response rates were assessed by the modified Third International Workshop on WM Response Criteria.

Results:TwelveRRWM patients received ibrutinib monotherapy for active/symptomatic WM during the study period; median follow up of the entire cohort was 29 months for the subset that received ibrutinib as salvage therapy. The median time on therapy for the entire cohort was 12.5 months. WM IPSS score was calculated intermediate in three patients and high in nine patients. MYD88 mutation status was assessed in five patients and detected positive at the time of WM diagnose. Before therapy, six of the 12 (50%) had a serum level of 3000 mg per deciliter or higher; after treatment, at the time of best response, two of the 12 patients (16.6%) had a serum IgM level of 3000 mg per deciliter or higher. ECOG performance score was 1 in 75% of our cohort. The median lines of prior therapy for the RRWM were 3 (range: 2-8). Only two patients had received autologous stem cell transplantation (ASCT) prior to ibrutinib monotherapy. Responses included a complete response in three patients, a very good response in 1 patient and a partial response in six patients, representing overall response of 83.3%. The remaining two patients discontinued ibrutinib due to progressive disease. No several adverse events due to ibrutinib were observed in our cohort. At the time of data collection, one patient had deceased.

Conclusion:Ibrutinib is an effective drug, associated with durable responses, and safety for both previously-treated and newly diagnosed WM. Our study has several limitations that should be considered when reviewing the results, including the retrospective design and inclusion of a small number of patients. Nevertheless, because of the rarity of the diseases, our data provide useful information on the use of ibrutinib in patients with heavily pretreated WM.