Randomized Comparison of Rituximab Versus Bortezomib Plus Cyclophosphamide and Dexamethasone in Newly Diagnosed Waldenstrom Macroglobulinemia Patients

Background:Waldenstrom's macroglobulinemia (WM) is one type of lymphoma that had the characteristic of both lymphocytes and plasma cells. Rituximab-based or bortezomib-based regiments are commonly used treatment approaches in routine practice in previously untreated patients with LPL/WM. However, which regiment is better still unknown. The purpose of this study is to compare the efficacy of RCD (Rituximab,cyclophosphamide and dexamethasone) and BCD (Bortezomib, cyclophosphamide and dexamethasone)in newly diagnosed WM patients.

Methods:30 newly diagnosed WM patients were randomly assigned to BCD or RCD group for introduction chemotherapy. Chemotherapeutic response was evaluated after 3 cycles. If a minor response (MR) or better response achieves, addition 3 cycles will be given. If not, patients will be crossed to control group for another 3 cycles. If a MR or better response comes out, addition 3 cycles will be given, otherwise, the patients will quit this study.

Results: Finally, 15 patients were assigned to each treatment group. The basic characteristics of the two groups were similar. The median time to response in RCD and BCD group were 4 months and 3 months, respectively. The CR rate in RCD and BCD group was 20% and 26.7% respectively, with VGPR rate 26.7% and 6.7%, PR rate 46.7% and 40% in each group respectively. Additional 20% minor response was observed in BCD group. The overall response was 86.7% in both groups. However, RCD group had higher good response rate (≥VGPR) compared to BCD ( 46.7% vs 33.4%, p=0.05). The rate of major response (≥PR) in RCD group was higher than that in BCD group (86.7% vs 66.7%, p=0.195). The median follow-up time was 29 months. The median duration of response in RCD and BCD group was 35 months and 30 months, respectively. The 3-year progression-free rate of RCD group was significantly higher than that of the BCD group (87.5% vs 39.2%,p=0.045). The 3-year overall survival rate was 100% with RCD group versus 70% with BCD group (100% vs 70%, p=0.127)The most common adverse events of any grade with RCD and BCD were hematological toxicity. 3 patients in the RCD group had grade 3 or higher granulocytopenia.4 patients in the BCD group occurred grade 3 or higher hypocytosis. Other adverse event in the RCD group included pneumonia (40%), non-infectious fever (26.7%), hyperglycemia (13.3%) and rash (6.7%).The most common non-hematological adverse event in BCD group were peripheral neuropathy (40%), pneumonia (26.7%), herpes zoster (13.3%) and ventosity(6.7%). Events of non-infectious fever occurred more frequently in the RCD group (26.7% vs 0%, p=0.032). However, peripheral neuropathy was more common in the BCD group (40% vs 6.7%, p=0.031). There was no serious non-hematological grade 3 or higher adverse events occurred in the both groups.

Conclusion: The RCD and BCD regimens have similar overall response in newly diagnosed WM. RCD regimen has higher good response rate and longer PFS time compared to BCD regimen. Both regimens have good tolerance.