Assessing Frontline Therapy with Bendamustine-Rituximab in Patients with Treatment-Naïve Waldenstrom Macroglobulinemia

Patients with treatment-naïve Waldenström macroglobulinemia (WM) who receive frontline immunochemotherapy have excellent outcomes that can be achieved with a finite course of therapy, according to the findings of a study conducted by Jowon Laura Kim, MD, and colleagues. Results were presented at the 2021 American Society of Hematology Annual Meeting.

Researchers used the BC Cancer Centre for Lymphoid Cancer Database to assess 111 patients with previously untreated WM (median age = 69 years) who were treated with bendamustine-rituximab (BR) (n = 57) or R-CVP chemotherapy (n = 54) as frontline therapy between August 2004 and August 2020. For inclusion, patients were required to have clinicopathologically confirmed lymphoplasmacytic lymphoma and measurable monoclonal IgM. The outcomes of interest were event-free survival (EFS), defined as time from start of immunochemotherapy to progression, relapse, initiation of alternative therapy, histologic transformation, or death due to any cause, and early progression (POD24; defined as relapse or progression, death from lymphoma, or treatment toxicity within 24 months of initiation of systemic therapy). These outcomes were compared with a historical cohort of patients treated with frontline R-CVP.

According to the results, a higher proportion of R-CVP-treated patients received four or more cycles of chemotherapy (81% vs. 65%; p = 0.049). Following immunochemotherapy, 68% received maintenance rituximab, with 63% and 72% in the BR and R-CVP groups, respectively (p = 0.3). The researchers noted that EFS was established at 6.3 years for R-CVP due to longer duration of follow-up. Overall survival (OS) estimates at 4 years were found to be robust, at 74% and 81% for BR and R-CVP, respectively (p = 0.6). A sub-analysis of only patients administered at least cycles of immunochemotherapy also showed no clear difference in outcomes between BR and R-CVP.

Furthermore, the median time to transformation was 6.5 years, with only three late biopsy-proven events, according to the researchers. POD24 occurred in 18% of patients, with inferior survival observed in patients who had an early event compared with a reference cohort; however, the researchers stated, this observation did not reach statistical significance (p = 0.3)

“This population-based analysis of treatment-naïve WM patients treated with upfront immunochemotherapy confirms the excellent outcomes that can be achieved with a finite course of therapy,” the researchers concluded. “In contrast to prior studies, similar outcomes were observed with R-CVP and BR. Further, regardless of frontline therapy, POD24 may be associated with inferior outcome but larger studies are needed.”