TY - JOUR
T1 - Randomized trial of ofatumumab and bendamustine versus ofatumumab, bendamustine, and bortezomib in previously untreated patients with high-risk follicular lymphoma
T2 - CALGB 50904 (Alliance)
AU - Blum, Kristie A.
AU - Polley, Mei Yin
AU - Jung, Sin Ho
AU - Dockter, Travis J.
AU - Anderson, Sarah
AU - Hsi, Eric D.
AU - Wagner-Johnston, Nina
AU - Christian, Beth
AU - Atkins, Jim
AU - Cheson, Bruce D.
AU - Leonard, John P.
AU - Bartlett, Nancy L.
N1 - Funding Information:
The research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award numbers U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology) and U10CA180833, U10CA180850, and UG1CA189858. It was also supported in part by funds from Novartis (GlaxoSmithKline). Kristie A. Blum is supported by the National Institutes of Health (NIH-K24CA201524). The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. Eric D. Hsi serves on advisory boards for Seattle Genetics, Jazz, and Celgene and reports research funding to his institution from AbbVie and Eli Lilly. Nina Wagner-Johnston serves on advisory boards for Bayer, Gilead, Janssen, ADC Therapeutics, and JUNO and reports clinical research funding provided to her institution from Astex, Merck, and Regeneron. Beth Christian reports clinical research funding provided to her institution from Teva Pharmaceuticals as well as research funding from Genentech, Triphase, Celgene, Merck, Seattle Genetics, Janssen, Acerta, and Cephalon outside the submitted work. Bruce D. Cheson reports consulting fees from AbbVie, AstraZeneca, Roche-Genentech, TG Therapeutics, Epizyme, Morphosys, and Celgene; personal fees from Symbiopharma, Astellas, Gilead, Pharmacyclics, and Reddy Pharmaceuticals; and clinical research funding to his institution from AbbVie, AstraZeneca, Roche-Genentech, TG Therapeutics, Epizyme, Celgene, and Trillium. John P. Leonard reports personal fees from Celgene, Gilead, Teva, ADC Therapeutics, AbbVie, Genmab, Biotest, Regeneron, Roche/Genentech, Sutro, Sunesis, Bristol-Myers Squibb, Epizyme, Pfizer, Bayer, United Therapeutics, MEI Pharma, Novartis, Merck, Morphosys, BeiGene, AstraZeneca, Nordic Nanovector, Karyopharm, Sandoz, Miltenyi, and Akcea Therapeutics outside the submitted work. The other authors made no disclosures.
Publisher Copyright:
© 2019 American Cancer Society
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
KW - bendamustine
KW - bortezomib
KW - follicular lymphoma
KW - ofatumumab
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U2 - 10.1002/cncr.32289
DO - 10.1002/cncr.32289
M3 - Article
C2 - 31174236
AN - SCOPUS:85067840888
SN - 0008-543X
VL - 125
SP - 3378
EP - 3389
JO - Cancer
JF - Cancer
IS - 19
ER -