Adding bortezomib to ofatumumab and bendamustine failed to improve response and survival outcomes compared with ofatumumab and bendamustine alone in patients with previously untreated high-risk follicular lymphoma, according to the phase II results of the Cancer and Leukemia Group B (CALGB) 50904 trial.
In addition, more patients treated with bortezomib required dose modifications and early discontinuation.
“The addition of bortezomib to ofatumumab and bendamustine does not improve overall responses, complete responses, or progression-free survival in patients with previously untreated follicular lymphoma,” wrote study researcher Kristie A. Blum, MD, of Winship Cancer Institute at Emory University in Atlanta, and colleagues, in Cancer. “Although this study took 5 years to accrue, the trial demonstrates that studies are feasible for high-risk follicular lymphoma and that excellent overall responses, complete responses, and durable remissions occur with bendamustine-based chemotherapy in this population despite the adverse prognostic features.”
CALGB 50904 was designed based on the efficacy of bortezomib combined with rituximab and bendamustine seen in patients with relapsed follicular lymphoma, and the promising activity of the anti-CD20 antibody ofatumumab.
The trial included 128 patients with grade 1 to 3a follicular lymphoma and a Follicular Lymphoma International Prognostic Index (FLIPI) score of 2 with 1 lymph node larger than 6 cm or a FLIPI score of 3 to 5. Patients were randomly assigned to ofatumumab, bendamustine, and maintenance ofatumumab (arm A) or ofatumumab, bendamustine, and bortezomib with maintenance ofatumumab and bortezomib (arm B).
In arm A, the majority of patients (86%) completed induction and 64% completed maintenance. In arm B, 66% completed induction and only around half of patients (52%) completed maintenance.
Grade 3/4 adverse events were similar in both treatment arms, with common toxicities including neutropenia, nausea/vomiting, diarrhea, and sensory neuropathy. Dose modifications were required by 65% of patients in arm A and 89% of patients in arm B.
The researchers noted that “serious infusion reactions, infections, and second malignancies can occur when anti-CD20 antibodies are combined with bendamustine, and physicians need to monitor patients for acute and late risks of therapy.”
The estimated overall response rate was 95% in both arms. The estimated complete response rate was 62% in arm A and 60% in patients with added bortezomib. With a median follow-up of 3.3 years, there was no significant difference between arm A and arm B for progression-free survival (80% vs 76%) or overall survival (97% vs 91%).
“This study demonstrated significant efficacy with bendamustine-based chemoimmunotherapy in patients with follicular lymphoma with high-risk features at diagnosis,” the researchers wrote. “Specifically, the overall response rate of more than 90% and the complete response rate of 60% observed in this trial compare favorably with historical data.”
However, the researchers cautioned comparison of CALGB 50904 data with historical data “because observed differences in efficacy could be attributed to difference in patient populations, treatments, and response assessments.”