Half-Dose R-CHOP May Be Effective, Reduce Toxicity, in Waldenström Macroglobulinemia

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Due to its rarity, there is neither robust evidence nor many completed studies supporting specific treatment regimens in Waldenström macroglobulinemia.
Due to its rarity, there is neither robust evidence nor many completed studies supporting specific treatment regimens in Waldenström macroglobulinemia.

A half-dose regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) may have a favorable safety profile and be effective as a primary therapy among untreated patients with Waldenström macroglobulinemia (WM), according to a study published in Blood Research.1

WM is a hematological malignancy that, due to its rarity, does not have much robust evidence supporting a specific treatment regimen. R-CHOP is one of the most widely recommended standard regimens, but is associated with severe myelosuppression and peripheral neuropathy. New management strategies are needed for this patient population. 

For this study, researchers retrospectively analyzed the clinical data and outcomes of 20 patients with previously untreated WM who received 6 cycles of half-dose R-CHOP every 3 weeks; 16 (80%) received the intervention without vincristine. Patients eligible for analysis had symptomatic WM, which was defined as the presence of constitutional symptoms, cytopenia, organomegaly, and/or symptoms from monoclonal IgM protein such as hyperviscosity syndrome and cold agglutinin disease. 

After a median follow-up of 26.3 months, results showed that 13 (65%) patients responded to treatment, which consisted of 2 (10%) complete responses (CR), 1 (5%) very good partial response (VGPR), 10 (50%) partial responses (PR), and 4 (20%) minor responses. The median time for response and best response were 6 weeks and 9.9 weeks, respectively. 

The 2-year progression-free survival (PFS) rate was 70%, and the 2-year overall survival rate was 93.3%. 

Overall, grade 3 to grade 4 leukocytopenia was observed in 6 patients (32%), neutropenia in 7 patients (37%), febrile neutropenia in 0 patients, and grade 1 peripheral neuropathy in 4 patients (21%). No patients required dose adjustments due to toxicities. 

The authors concluded that the half-dose R-CHOP regimen is a reasonable option for primary therapy in patients with untreated, symptomatic WM. “To the best of our knowledge, this is the first study to report the use of a reduced-dose CHOP regimen combined with [rituximab] for the primary treatment of WM,” they wrote. “Further large-scale prospective studies are warranted.”

Reference

  1. Sekiguchi N, Hamano A, Kitagawa T, et al. Impact of rituximab and half-dose CHOP as primary therapy for untreated symptomatic Waldenström Macroglobulinemia: review of a combined regimen of rituximab with an alkylating agent[published online June 25, 2018]. Blood Res. doi: 10.5045/br.2018.53.2.117

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