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

• Published in: Cancer Vol. 125; no. 19; pp. 3378 - 3389
• Main Authors: Blum, Kristie A., Polley, Mei‐Yin, Jung, Sin‐Ho, Dockter, Travis J., Anderson, Sarah, Hsi, Eric D., Wagner‐Johnston, Nina, Christian, Beth, Atkins, Jim, Cheson, Bruce D., Leonard, John P., Bartlett, Nancy L.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-10-2019
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; bendamustine; Bendamustine Hydrochloride - administration & dosage; Bendamustine Hydrochloride - adverse effects; Bortezomib; Bortezomib - administration & dosage; Bortezomib - adverse effects; Confidence intervals; Diarrhea; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; follicular lymphoma; Humans; Lymph nodes; Lymphoma; Lymphoma, Follicular - drug therapy; Lymphoma, Follicular - mortality; Lymphoma, Follicular - pathology; Maintenance; Male; Middle Aged; Nausea; Neoplasm Grading; Neuropathy; Neutropenia; ofatumumab; Oncology; Progression-Free Survival; Remission Induction - methods; Risk; Survival; Toxicity; Vomiting; follicular lymphoma; bortezomib; ofatumumab; bendamustine
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.32289

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.
This randomized, multicenter phase 2 trial demonstrates no benefit with the addition of bortezomib to frontline ofatumumab and bendamustine in patients with high‐risk follicular lymphoma, which is defined as a Follicular Lymphoma International Prognostic Index (FLIPI) score of 3 to 5 or an FLIPI score of 2 with at least 1 lymph node >6 cm. The overall response (OR) rate is 91% with a complete response (CR) rate of 60% and a 2‐year progression‐free survival (PFS) rate of 75.6% for 62 patients treated with ofatumumab, bendamustine, and bortezomib, whereas the OR rate is 95% with a CR of 62% and a 2‐year PFS rate of 80.3% for 66 patients treated with ofatumumab and bendamustine.