Randomized trial of ofatumumab and bendamustine versus ofatumumab, bendamustine, and bortezomib in previously untreated patients with high-risk follicular lymphoma

CALGB 50904 (Alliance)

Kristie A. Blum, Mei Yin Polley, Sin Ho Jung, Travis J. Dockter, Sarah Anderson, Eric D. Hsi, Nina Wagner-Johnston, Beth Christian, Jim Atkins, Bruce D. Cheson, John P. Leonard, Nancy L. Bartlett

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalCancer
DOIs
StatePublished - Jan 1 2019

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Follicular Lymphoma
Maintenance
Disease-Free Survival
Confidence Intervals
Bortezomib
Bendamustine Hydrochloride
ofatumumab
Neutropenia
Nausea
Vomiting
Diarrhea
Survival Rate
Lymph Nodes
Safety
Survival

Keywords

  • bendamustine
  • bortezomib
  • follicular lymphoma
  • ofatumumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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

In: Cancer, 01.01.2019.

Research output: Contribution to journalArticle

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. / Randomized trial of ofatumumab and bendamustine versus ofatumumab, bendamustine, and bortezomib in previously untreated patients with high-risk follicular lymphoma : CALGB 50904 (Alliance). In: Cancer. 2019.
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title = "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.",
keywords = "bendamustine, bortezomib, follicular lymphoma, ofatumumab",
author = "Blum, {Kristie A.} and Polley, {Mei Yin} and Jung, {Sin Ho} and Dockter, {Travis J.} and Sarah Anderson and Hsi, {Eric D.} and Nina Wagner-Johnston and Beth Christian and Jim Atkins and Cheson, {Bruce D.} and Leonard, {John P.} and Bartlett, {Nancy L.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/cncr.32289",
language = "English (US)",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",

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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.

PY - 2019/1/1

Y1 - 2019/1/1

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

JO - Cancer

JF - Cancer

SN - 0008-543X

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