Randomized trial of ofatumumab and bendamustine versus ofatumumab, bendamustine, and bortezomib in previously untreated patients with high-risk follicular lymphoma: CALGB 50904 (Alliance)

Abstract

Background: This multicenter, randomized phase 2 trial evaluated complete responses (CRs), efficacy, and safety with ofatumumab and bendamustine and with ofatumumab, bendamustine, and bortezomib in patients with untreated, high-risk follicular lymphoma (FL).

Methods: Patients with grade 1 to 3a FL and either a Follicular Lymphoma International Prognostic Index (FLIPI) score of 2 with 1 lymph node >6 cm or an FLIPI score of 3 to 5 were randomized to arm A (ofatumumab, bendamustine, and maintenance ofatumumab) or to arm B (ofatumumab, bendamustine, bortezomib, and maintenance ofatumumab and bortezomib).

Results: One hundred twenty-eight patients (66 in arm A and 62 in arm B) received treatment. The median age was 61 years, and 61% had disease >6 cm; 29% had an FLIPI score of 2, and 71% had an FLIPI score of 3 to 5. In arm A, 86% completed induction, and 64% completed maintenance. In arm B, 66% and 52% completed induction and maintenance, respectively. Dose modifications were required in 65% and 89% in arms A and B, respectively. Clinically significant grade 3 to 4 toxicities included neutropenia (A, 36%; B, 31%), nausea/vomiting (A, 0%; B, 8%), diarrhea (A, 5%; B, 11%), and sensory neuropathy (A, 0%; B, 5%). The estimated CR rates were 62% (95% confidence interval [CI], 50%-74%) and 60% (95% CI, 47%-72%) in arms A and B, respectively (P = .68). With a median follow-up of 3.3 years, the estimated 2-year progression-free survival (PFS) and overall survival (OS) rates were 80% and 97%, respectively, for arm A and 76% and 91%, respectively, for arm B.

Conclusions: The CR rates, PFS, and OS were not improved with the addition of bortezomib to ofatumumab and bendamustine in patients with high-risk FL. Although grade 3 to 4 toxicities were similar, more patients treated with bortezomib required dose modifications and early discontinuation.

Trial registration: ClinicalTrials.gov NCT01286272.

Keywords: bendamustine; bortezomib; follicular lymphoma; ofatumumab.

Conflict of interest statement

Conflict of Interest Disclosure:

This trial was supported in part by funds from Novartis (GSK). Dr. Beth Christian receives clinical research funding provided to her institution from Teva pharmaceuticals. Dr. Bruce Cheson receives consulting fees from Abbvie, Astra Zeneca, Roce-Genentech, TG Therapeutics, Epizyme, Morphosys, and Celgene. Dr. Cheson receives clinical research funding to his institution from Abbvie, Astra Zeneca, Roche-Genentech, TG Therapeutics, Epizyme, Celgene and Trillium. Dr. Eric Hsi serves on advisory boards for Seattle Genetics, Jazz, and Celgene. Dr. Hsi receives research funding to his institution from Abbvie and Eli Lilly. Dr. Nina Wagner-Johnston serves on advisory boards for Bayer and JUNO. Dr. Nina Wagner-Johnston receives clinical research funding provided to her institution from Astex, Merck, and Regeneron. The remaining authors have no additional conflicts to disclose.

© 2019 American Cancer Society.

Figures

Figure 1.

Study treatment

Figure 2.

Forest plot for subgroup analysis of CR by treatment arm: Arm A received ofatumumab and bendamustine and Arm B received ofatumumab, bendamustine, and bortezomib

Figure 3.

Progression-free survival by treatment arm: Arm A received ofatumumab and bendamustine and Arm B received ofatumumab, bendamustine and bortezomib.

Figure 4.

Overall survival by treatment arm: Arm A received ofatumumab and bendamustine and Arm B received ofatumumab, bendamustine and bortezomib.