Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-Cell lymphoma: a phase II study.

Abstract

PURPOSE:

Lenalidomide has significant single-agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). We demonstrated that lenalidomide can be safely combined with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone); this new combination is known as R2CHOP. The goal of this phase II study was to evaluate the efficacy of this combination in newly diagnosed DLBCL.

PATIENTS AND METHODS:

Eligible patients were adults with newly diagnosed untreated stages II to IV CD20(+) DLBCL. Patients received lenalidomide 25 mg orally per day on days 1 through 10 with standard-dose R-CHOP every 21 days for six cycles. All patients received pegfilgrastim on day 2 of each cycle and aspirin prophylaxis throughout. DLBCL molecular subtype was determined by tumor immunohistochemistry and classified as germinal center B-cell (GCB) versus non-GCB in the R2CHOP patients and 87 control patients with DLBCL from the Lymphoma Database who were treated with conventional R-CHOP.

RESULTS:

In all, 64 patients with DLBCL were enrolled, and 60 were evaluable for response. The overall response rate was 98% (59 of 60) with 80% (48 of 60) achieving complete response. Event-free survival and overall survival (OS) rates at 24 months were 59% (95% CI, 48% to 74%) and 78% (95% CI, 68% to 90%), respectively. In R-CHOP patients, 24-month progression-free survival (PFS) and OS were 28% versus 64% (P < .001) and 46% versus 78% (P < .001) in non-GCB DLBCL versus GCB DLBCL, respectively. In contrast, there was no difference in 24-month PFS or OS for R2CHOP patients on the basis of non-GCB and GCB subtype (60% v 59% [P = .83] and 83% v 75% [P = .61] at 2 years, respectively).

CONCLUSION:

R2CHOP shows promising efficacy in DLBCL. The addition of lenalidomide appears to mitigate a negative impact of non-GCB phenotype on patient outcome.

• Authors: Grzegorz S Nowakowski, Betsy LaPlant, William R Macon, Craig B Reeder, James M Foran, Garth D Nelson, Carrie A Thompson, Candido E Rivera, David J Inwards, Ivana N Micallef, Patrick B Johnston, Luis F Porrata, Stephen M Ansell, Randy D Gascoyne, Thomas M Habermann, Thomas E Witzig
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 33 Issue 3 Pg. 251-7 (Jan 20 2015) ISSN: 1527-7755 [Electronic] United States
• PMID: 25135992 (Publication Type: Clinical Trial, Phase II, Journal Article)
• Copyright: © 2014 by American Society of Clinical Oncology.

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Immunologic Factors
• R-CHOP protocol
• Rituximab
• Thalidomide
• Vincristine
• Doxorubicin
• Cyclophosphamide
• Lenalidomide
• Prednisone

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Murine-Derived (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Doxorubicin (administration & dosage)
• Drug Administration Schedule
• Female
• Humans
• Immunologic Factors (therapeutic use)
• Kaplan-Meier Estimate
• Lenalidomide
• Lymphoma, Large B-Cell, Diffuse (drug therapy, pathology)
• Male
• Middle Aged
• Phenotype
• Prednisone (administration & dosage)
• Prognosis
• Rituximab
• Thalidomide (analogs & derivatives, therapeutic use)
• Treatment Outcome
• Vincristine (administration & dosage)