Title | Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Ruan J, Martin P, Furman RR, Lee SM, Cheung K, Vose JM, Lacasce A, Morrison J, Elstrom R, Ely S, Chadburn A, Cesarman E, Coleman M, Leonard JP |
Journal | J Clin Oncol |
Volume | 29 |
Issue | 6 |
Pagination | 690-7 |
Date Published | 2011 Feb 20 |
ISSN | 1527-7755 |
Keywords | Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Combined Chemotherapy Protocols, Boronic Acids, Bortezomib, Cyclophosphamide, Disease-Free Survival, Doxorubicin, Female, Humans, Immunohistochemistry, Kaplan-Meier Estimate, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell, Male, Middle Aged, Prednisone, Pyrazines, Rituximab, Treatment Outcome, Vincristine, Young Adult |
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/m(2) (n = 4), 1.0 mg/m(2) (n = 9), or 1.3 mg/m(2) (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. |
DOI | 10.1200/JCO.2010.31.1142 |
Alternate Journal | J Clin Oncol |
PubMed ID | 21189393 |
Related Faculty:
Amy Chadburn, M.D. Ethel Cesarman, M.D., Ph.D.