B-DRC Combination Treatment Yielded High Response Rates Among Patients With Waldenström Macroglobulinemia

Results from a Prospective Randomized Trial

According to findings from a randomized trial recently published in the Journal of Clinical Oncology, the use of bortezomib-dexamethasone, rituximab, and cyclophosphamide (B-DRC) as a first-line combination treatment yielded tolerable safety and increased response rates among patients with Waldenström macroglobulinemia (WM). 

Christian Buske, MD, University Hospital of Ulm, Ulm, Germany, and coauthors explained that previous research has indicated “Rituximab/chemotherapy is a cornerstone of treatment for Waldenström macroglobulinemia.” They aimed to expand this research by evaluating the efficacy and safety of dexamethasone, rituximab, and cyclophosphamide (DRC), and the addition of bortezomib to this combination (B-DRC), as a first-line treatment for WM. 

Dr Buske and coauthors aimed to reach a primary endpoint of progression-free survival (PFS), as well as secondary endpoints including overall response rate, overall survival, and safety/tolerability. 

204 patients with WM who had never undergone treatment were enrolled in this study and randomly assigned to receive either DRC or B-DRC for a total of 6 cycles. 

At a median follow-up of 27.5 months, the estimated 24-month PFS was 80.6% for the B-DRC arm and 72.8% for the DRC arm. By the end of treatment, 80.6% of patients in the B-DRC arm experienced major responses due to treatment, versus 69.9% in the DRC arm. 17.2% of patients in the B-DRC arm experienced a complete response/very good partial response, versus 9.6% in the DRC arm, respectively. 

The median time to first response was 3 months in the B-DRC arm versus 5.5 months in the DRC arm, leading to higher major response rates after 3 cycles of B-DRC (57%) compared to 3 cycles of DRC (32.5%). Treatments were well-tolerated and safe across both arms, with grade ≥ 3 adverse events observed in 49.2% of all patients. 

In conclusion, these results indicate that B-DRC is a viable treatment option for patients with WM. As endpoints were met, Dr Buske et al stated, “Fixed duration immunochemotherapy remains an important pillar in the clinical management of WM.”

Journal of Clinical Oncology Associate Editor Suzanne Lentzsch, MD, PhD, stated that B-DRC treatment is “especially beneficial for patients with higher tumor burden requiring a faster response.” She added that unlike “BTK inhibitors, the fixed duration of B-DRC improves tolerability in an elderly patient population.” 

Source:

Buske C, Dimopoulos M, Grunenberg A, et al. Bortezomib-dexamethasone, rituximab, and cyclophosphamide as first-line treatment for Waldenström's macroglobulinemia: A prospectively randomized trial of the European consortium for Waldenström's macroglobulinemia. J Clin Oncol. Published online February 10, 2023. doi:https://doi.org/10.1200/jco.22.01805