Bortezomib plus Dexamethasone versus Fludarabine plus Cyclophosphamide in initial treatment of patients with Waldenström macroglobulinemia

We examined the efficacy of bortezomib plus dexamethasone(BD) versus fludarabine plus cyclophosphamide(FC) in patients with symptomatic, untreated Waldenström macroglobulinemia(WM). Furthermore, to evaluate the toxicity of BD regimen in WM. Patients and methods: 17 untreated WM patients received either bortezomib and dexamethasone(n=7) or fludarabine and cyclophosphamide(n=10). BD group: A cycle of therapy consisted of bortezomib 1.3 mg/m2 intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11. Patients received 4 cycles at least. FC group: A cycle of therapy consisted of fludarabine 25 mg/m2 on days 1-3; cyclophosphamide 250mg/m2 on days 1-3. Patients received 4-6 consecutive cycles for induction therapy. Responses were based on paraprotein levels. Herpes zoster prophylaxis was instituted with using oral valacyclovir. Results: In BD and FC groups, the overall response rates(PR+MR) were 86% versus 70% respectively. There was not complete response in two groups. In BD and FC groups, minor and partial responses occurred at a median of 25 vs. 54 days and 55 vs. 94 days respectively(P<0.05, respectively). The median progression-free survival(PFS) was 27 months, and a median follow-up of 62 months the actuarial 5-year overall survival(OS) rate was 80% in FC group. Because of a short following time, there were not PFS and OS that can be observed in BD group. Hemoglobin and platelet levels increased normally in 83% vs. 50% and 100% vs. 66% patients in BD and FC groups respectively(P<0.05, respectively). In BD group, peripheral neuropathy was the most common toxicity(57% grade 1- 2, no grade 3- 4). Hematologic toxicities included grade 3 to 4 thrombocytopenia in 2/7(28%) and neutropenia in 1/7(14%). 42% patients developed herpes zoster. Conclusions: The results demonstrate that BD produces rapid responses, along with high rates of response in WM, and it was generally well-tolerated in our study. Herpes zoster prophylaxis is necessary with BD, and peripheral neuropathy was the most common toxicity, but not leading to discontinuance of BD. This retrospective analysis confirms that BD therapy is an effective initial treatment in WM.

No relevant conflicts of interest to declare.