A phase II study of bortezomib added to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients with previously untreated indolent non-Hodgkin's lymphoma

• Type of Material: Article
• Authors: Jonathon Cohen, Emory University; Jeffrey M. Switchenko, Emory University; Jean Koff, Emory University; Rajni Sinha, Emory University; Jonathan Kaufman, Emory University; Hanna Khoury, Emory University; Nassoma Bumpers, Emory University; Amanda Colbert, Emory University; Amanda Hutchison-Rzepka, Emory University; Loretta J. Nastoupil, Emory University; Leonard Heffner Jr., Emory University; Amelia Langston, Emory University; Mary Lechowicz, Emory University; Sagar Lonial, Emory University; Christopher Flowers, Emory University
• Language: English
• Date: 2015-11-01
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 John Wiley & Sons Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1111/bjh.13637
• Title of Journal or Parent Work: British Journal of Haematology
• ISSN: 0007-1048
• Volume: 171
• Issue: 4
• Start Page: 539
• End Page: 546
• Grant/Funding Information: Dr. Cohen is a Lymphoma Research Foundation scholar.; Research reported in this publication was supported in part by the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292.; Support for the conduct of this trial was provided by Millennium.
• Keywords: indolent lymphoma; STAGE FOLLICULAR LYMPHOMA; Life Sciences & Biomedicine; neuropathy; bortezomib; CHOP PLUS RITUXIMAB; Hematology; LOW-GRADE; B-CELL LYMPHOMA; non-Hodgkin lymphoma; R-CVP; MANTLE-CELL; NATIONAL LYMPHOCARE; follicular lymphoma; INTERNATIONAL PROGNOSTIC INDEX; Science & Technology; 1ST-LINE TREATMENT
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Oncology

Abstract

Bortezomib-containing combinations are active in non-Hodgkin lymphoma (NHL) although peripheral neuropathy can limit their dose intensity. Based on our phase I findings, we conducted a phase II trial of bortezomib in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with a modified dose of vincristine. Patients with untreated indolent NHL received bortezomib (1·6 mg/m2) on days 1 and 8 of a 21-day cycle for up to 8 cycles and R-CHOP with a 1·5 mg cap of vincristine. Patients achieving a complete response (CR) received maintenance rituximab, and remaining patients received maintenance rituximab and bortezomib. The primary endpoint was CR rate; secondary survival analyses were evaluated using the Kaplan-Meier method. Among 29 eligible patients, NHL morphologies included follicular (n = 20), marginal zone (n = 5) and small lymphocytic lymphoma (n = 4). Nineteen patients had CR (66%) and 10 had partial response (34%), yielding a 100% overall response rate. With a median follow-up of 48·7 months, the 4-year progression-free and overall survivals were 83% and 93%. Twenty-two patients experienced peripheral neuropathy of any grade, and two had grade 3 neuropathy. The combination of bortezomib with R-CHOP is effective for indolent NHL, and we plan to evaluate therapies incorporating novel proteasome inhibitors in future studies in NHL.