Deepening of response after completing rituximab‐containing therapy in patients with Waldenstrom macroglobulinemia

Abstract

Rituximab‐containing regimens are commonly used for frontline therapy in patients with symptomatic Waldenström macroglobulinemia (WM). We had observed that a portion of WM patients experienced deepening of response months to years after therapy completion. We carried a retrospective study aimed at describing this phenomenon. We gathered baseline data, and responses at end of induction, end of maintenance and best response. Deepening of response was defined as ≥25% decrease in serum IgM achieved at a later time from therapy completion. Of 178 patients included, 116 (65%) received maintenance therapy and 62 (35%) were observed. In patients who received maintenance, 44 (38%) had ≥25% decrease in serum IgM level after the end of maintenance with a median time from end of maintenance to lowest IgM level of 1.6 years (range 0.1‐7.9 years). In patients who were observed, 19 (31%) had ≥25% decrease in serum IgM level after the end of induction with a median time from end of induction to lowest IgM level of 1.6 years (range 0.2‐5.1 years). Baseline hemoglobin <11.5 g/dL, bone marrow involvement ≥50%, CXCR4 mutations and serum IgM ≥4000 mg/dL were associated with lower odds of deepening of response after therapy completion. Deepening of response was associated with better progression‐free survival (PFS; HR 0.46, 95% CI 0.26‐0.80; P = .006) and better survival after frontline treatment initiation (SAFTI; HR 0.21, 95% CI 0.06‐0.73; P = .01). In conclusion, deepening of response occurs in one third of WM patients after completing rituximab‐containing regimens and was associated with better PFS and SAFTI.

Assessment of fixed‐duration therapies for treatment‐naïve Waldenström macroglobulinemia

“…26,27 By contrast, in our study, fewer than 15% of patients in each arm received rituximab maintenance therapy. In an effort to avoid the biases resulting from deepening of the response with maintenance rituximab, 28 we also conducted a subset analysis after excluding the patients who had received rituximab maintenance. In this focused subset analysis, the patients treated with R-Benda had superior outcomes than those treated with DRC or BDR regimens.…”

O, wind, if winter comes … will symptoms be far behind?

“…Rituximab in combination with fludarabine resulted in a 76% overall response (OR) and 21% complete response (CR), with an estimated response duration of 77 months; however, the addition of fludarabine is associated with increased adverse events, including Grade 3–4 neutropenia in 41% 1,53 . Rituximab plus bendamustine was associated with a 71% OR and CR of 40%, 54 which actually increased in long‐term follow‐up, likely reflecting the delayed clearance of pathologic CA‐producing plasma cells 1,55 . The effect was also highly durable, with a median response duration not reached after 88 months 1 .…”