Cyclophosphamide and Rituximab With Bortezomib Highly Effective for Patients With Treatment-Naive Waldenström Macroglobulinemia

Findings from a Phase 2 Trial 

Cyclophosphamide and rituximab with bortezomib (BRC) demonstrated high efficacy and tolerability among patients with treatment-naive Waldenström macroglobulinemia (WM), according to a phase 2 trial published in Leukemia. Bone marrow B-cell depletion was independently associated with patient outcomes. 

Ruth de Tute, PhD, St James’s University Hospital, Leeds, United Kingdom, and coauthors stated, “There remains a lack of consensus as to the most appropriate primary therapy in Waldenström macroglobulinemia.” To expand on research regarding the best primary therapy for WM, the study authors aimed to assess the efficacy and safety of a novel bortezomib-based combination regimen and develop a sensitive WM-specific flow cytometry assay to evaluate bone-marrow response. The primary end point was the overall response rate among patients who received this regimen. 

In this phase 2 trial, 60 treatment-naive patients with WM were included. They were randomized on a 2 to 1 basis to receive cyclophosphamide and rituximab with either bortezomib or fludarabine (FCR). Results indicated that among the patients who received BRC (n = 41), the overall response rate was 97.6%. After a 62.6-month median follow-up, 65.9% (n = 27) of these patients remained alive without experiencing progression. The 2-year progression-free survival rate was 92.7%, the 3-year rate was 80.5%, and the 5-year rate was 65.5%. 

At the end of treatment, persistent WM B-cells were verifiable in 19 of 38 patients. Patients with bone marrow B-cell depletion experienced significantly longer progression-free survival compared to those who had detectable persistent bone marrow B-cells at the end of treatment. This continued to be independently associated after adjusting for baseline risk stratification or investigator-assessed response. 

Based on these findings, de Tute et al concluded, “BRC is a tolerable, highly efficacious regimen for treatment-naïve WM patients.”

“[Bone marrow] B-cell depletion is independently associated with patient outcomes,” they added. 

Source: 

de Tute R, Counsell N, Clifton-Hadley L, et al. Long-term outcomes by bone marrow B-cell depletion from the R2W trial of bortezomib with cyclophosphamide and rituximab in Waldenstrőm macroglobulinaemia. Leukemia. Published online: February 26, 2024. doi: 10.1038/s41375-024-02162-5