Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma

Jia Ruan, Peter Martin, Richard R. Furman, Shing M. Lee, Ken Cheung, Julie M. Vose, Ann LaCasce, Julia Morrison, Rebecca Elstrom, Scott Ely, Amy Chadburn, Ethel Cesarman, Morton Coleman, John P. Leonard

Research output: Contribution to journalArticle

248 Scopus citations

Abstract

Purpose: The proteasome inhibitor bortezomib may enhance activity of chemoimmunotherapy in lymphoma. We evaluated dose-escalated bortezomib plus standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus rituximab (R) in patients with diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). Patients and Methods: Seventy-six subjects with untreated DLBCL (n = 40) and MCL (n = 36) received standard CHOP every 21 days (CHOP-21) with R plus bortezomib at 0.7 mg/m2 (n = 4), 1.0 mg/m2 (n = 9), or 1.3 mg/m2 (n = 63) on days 1 and 4 for six cycles. Results: Median age was 63 years (range, 20 to 87), and International Prognostic Index (IPI) scores were generally unfavorable (39% with IPI of 2, and 49% with IPI of 3 to 5), as were Mantle Cell Lymphoma International Prognostic Index scores in patients with MCL (28% intermediate risk and 39% high risk). Toxicity was manageable, including neuropathy in 49 subjects (8% grade 2 and 4% grade 3) and grade 3/4 anemia (13%), neutropenia (41%), and thrombocytopenia (25%). For DLBCL, the evaluable overall response rate (ORR) was 100% with 86% complete response (CR)/CR unconfirmed (CRu; n = 35). Intent-to-treat (ITT, n = 40) ORR was 88% with 75% CR/CRu, 2-year progression-free survival (PFS) of 64% (95% CI, 47% to 77%) and 2-year overall survival (OS) of 70% (95% CI, 53% to 82%). For MCL, the evaluable ORR was 91% with 72% CR/CRu (n = 32). The ITT (n = 36) ORR was 81% with 64% CR/CRu, 2-year PFS 44% (95% CI, 27% to 60%) and 2-year OS 86% (95% CI, 70% to 94%). IPI and MIPI correlated with survival in DLBCL and MCL, respectively. Unlike in DLBCL treated with R-CHOP alone, nongerminal center B cell (non-GCB) and GCB subtypes had similar outcomes. Conclusion: Bortezomib with R-CHOP-21 can be safely administered and may enhance outcomes, particularly in non-GCB DLBCL, justifying randomized studies.

Original languageEnglish (US)
Pages (from-to)690-697
Number of pages8
JournalJournal of Clinical Oncology
Volume29
Issue number6
DOIs
StatePublished - Feb 20 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma'. Together they form a unique fingerprint.

  • Cite this

    Ruan, J., Martin, P., Furman, R. R., Lee, S. M., Cheung, K., Vose, J. M., LaCasce, A., Morrison, J., Elstrom, R., Ely, S., Chadburn, A., Cesarman, E., Coleman, M., & Leonard, J. P. (2011). Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma. Journal of Clinical Oncology, 29(6), 690-697. https://doi.org/10.1200/JCO.2010.31.1142