The role of tumor histogenesis, FDG-PET, and short-course EPOCH with dose-dense rituximab (SC-EPOCH-RR) in HIV-associated diffuse large B-cell lymphoma.
This is a phase 2 study to assess the role of tumor histogenesis (subtype), fluorodeoxyglucose positron emission tomography (FDG-PET), and short-course etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin with dose-dense rituximab (SC-EPOCH-RR) in newly diagnosed HIV-associated CD20(+) diffuse large B-cell lymphoma. Patients received a minimum of 3 and a maximum of 6 cycles with 1 cycle beyond stable radiographic and FDG-PET scans. Overall, 79% of patients received 3 cycles. Combination antiretroviral therapy was suspended before and resumed after therapy. Thirty-three enrolled patients had a median age of 42 years (range, 9-61 years), and 76% had a high-intermediate or high age-adjusted international prognostic index. At 5 years median follow-up, progression-free and overall survival were 84% and 68%, respectively. There were no treatment-related deaths or new opportunistic infections during treatment, and patients had sustained CD4 cell count recovery and HIV viral control after treatment. FDG-PET after 2 cycles had an excellent negative but poor positive predictive value. Tumor histogenesis was the only characteristic associated with lymphoma-specific outcome with 95% of germinal center B-cell (GCB) versus 44% of non-GCB diffuse large B-cell lymphoma (DLBCL) progression-free at 5 years. SC-EPOCH-RR is highly effective and less immunosuppressive with shorter duration therapy compared with standard strategies. However, new therapeutic advances are needed for non-GCB DLBCL, which remains the important cause of lymphoma-specific death. This trial was registered at www.clinicaltrials.gov as NCT000019253.
Dunleavy
Kieron
K
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Little
Richard F
RF
Pittaluga
Stefania
S
Grant
Nicole
N
Wayne
Alan S
AS
Carrasquillo
Jorge A
JA
Steinberg
Seth M
SM
Yarchoan
Robert
R
Jaffe
Elaine S
ES
Wilson
Wyndham H
WH
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D005047:Etoposide / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D019788:Fluorodeoxyglucose F18; D006678:HIV / Q000502:physiology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D011379:Prognosis; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000627:therapeutic use; D019562:Viral Load; D055815:Young Adult
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D019788:Fluorodeoxyglucose F18; D000069283:Rituximab; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone