A Phase II Trial of Bortezomib and Vorinostat in Mantle Cell Lymphoma and Diffuse Large B-cell Lymphoma

Overview

Journal Clin Lymphoma Myeloma Leuk

Publisher Elsevier

Specialty Oncology

Date 2018 Aug 21

PMID 30122201

Citations 17

Authors

Victor Yazbeck

Danielle Shafer

Edward B Perkins

Domenico Coppola

Lubomir Sokol

Kristy L Richards

Thomas Shea

Jia Ruan

Samir Parekh

Roger Strair

Christopher Flowers

David Morgan

Maciej Kmieciak

Prithviraj Bose

Amy Kimball

Ashraf Z Badros

Rachid Baz

Hui-Yi Lin

Xiuhua Zhao

Richard R Reich

Mary Beth Tombes

Ellen Shrader

Heidi Sankala

John D Roberts

Daniel Sullivan

Steven Grant

Beata Holkova

Affiliations

Soon will be listed here.

Abstract

Background: The proteasome inhibitor bortezomib has demonstrated marked preclinical activity when combined with the histone deacetylase inhibitor vorinostat in leukemia, multiple myeloma, and mantle cell lymphoma (MCL) cells. The present study evaluated the efficacy and safety of the combination in patients with relapsed or refractory MCL and diffuse large B-cell lymphoma (DLBCL).

Patients And Methods: The present multicenter, nonrandomized phase II trial used a Simon 2-stage design with 3 cohorts: cohort A, MCL with no previous bortezomib (including untreated MCL); cohort B, MCL with previous bortezomib; and cohort C, relapsed or refractory DLBCL with no previous bortezomib. Vorinostat (400 mg) was administered orally on days 1 to 5 and 8 to 12 before bortezomib (1.3 mg/m), which was administered intravenously on days 1, 4, 8, and 11 of each 21-day cycle.

Results: For the 65 treated patients (22 in cohort A, 4 in cohort B, and 39 in cohort C), the overall response rate was 31.8%, 0%, and 7.7%, respectively. The median progression-free survival was 7.6 months for cohort A and 1.8 months for cohort C. In cohort A, 7 patients had a partial response (PRs), 5 had stable disease (SD), 7 had progressive disease (PD), 1 was not assessed, and 2 were not evaluable. In cohort B, 2 had SD and 2 had PD. In cohort C, 3 had a PR, 8 had SD, 23 had PD, and 5 were not assessed. Baseline NF-κB activation, measured as nuclear RelA by immunohistochemistry, did not correlate with clinical response.

Conclusion: The combination of bortezomib and vorinostat is safe and has modest activity in MCL and limited activity in DLBCL.

Citing Articles

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Greve P, Meyer-Wentrup F, Peperzak V, Boes M Immunother Adv. 2022; 1(1):ltab001.

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Altered pathways and targeted therapy in double hit lymphoma.

Zhuang Y, Che J, Wu M, Guo Y, Xu Y, Dong X J Hematol Oncol. 2022; 15(1):26.

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Programmed cell death, redox imbalance, and cancer therapeutics.

Dai X, Wang D, Zhang J Apoptosis. 2021; 26(7-8):385-414.

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