B-DRC Produces Deep Remissions, Clinically Meaningful PFS Rates in Patients with Waldenstrom Macroglobulinemia

First-line treatment with bortezomib (B) plus dexamethasone, rituximab, and cyclophosphamide (DRC) was well tolerated and associated with deep remissions and prolonged progression-free survival (PFS) in patients with Waldenstrom macroglobulinemia (WM), according to results from a phase II trial.

Christian Buske, MD, of the University Hospital Ulm in Germany presented results from the trial =at the 62nd American Society of Hematology Annual Meeting & Exposition. In the trial, a total of 204 patients with WM were randomized to either DRC or B-DRC. The primary endpoint was PFS, and the secondary endpoints were response rates, overall survival (OS), and toxicity.

The median age of the study population was 68 years in both treatment arms. Overall, the median follow-up duration was 27.5 months at time of data cutoff. Approximately 73% of patients in both treatment arms were at intermediate risk, according to the International Prognostic Scoring System for WM, whereas 13% of patients in both arms were at high risk.

At time of data cutoff, the median PFS in the B-DRC arm had not been reached. In the DRC arm, the median PFS was 50.1 months. The estimated 24-month PFS rates were 80.6 % for the B-DRC group and 72.8% for the DRC arm.

Although B-DRC was associated with prolonged PFS, it was not significantly different than DRC alone. “Future trials will have to compare chemotherapy-free approaches such as continuous treatment with Bruton’s tyrosine kinase inhibitors with fixed duration treatments exemplified by B-DRC to understand which of the two treatment approaches offers the highest long-term sustained clinical benefit to [patients with] WM,” the researchers noted.

The median OS had not been reached in either treatment arm. There were five reported deaths in the B-DRC group and six in the DRC arm. At the end of treatment, B-DRC was associated with major responses in 79% of patients. In contrast, major responses were observed in 68.9% of patients randomized to DRC. The overall response rates were 91.2% for B-DRC versus 86.7% for DRC.

Both treatments were well tolerated, with grade ≥3 adverse events (AEs) observed in 48% of patients overall. The most common grade ≥3 AEs included neutropenia (25%), anemia (6%), and thrombocytopenia (5%).