Total body irradiation, etoposide, cyclophosphamide, and autologous peripheral blood stem-cell transplantation followed by randomization to therapy with interleukin-2 versus observation for patients with non-Hodgkin lymphoma: results of a phase 3 randomized trial by the Southwest Oncology Group (SWOG 9438).
To determine the effect of posttransplantation immunotherapy with IL-2 on the progression-free survival (PFS) and overall survival (OS) of patients with non-Hodgkin lymphoma (NHL) after autologous stem-cell transplantation (PBSCT), patients with previously treated NHL were treated with cyclophosphamide, etoposide, total body irradiation (TBI), and PBSCT. Twenty-eight to 80 days after PBSCT, patients were randomized to IL-2 versus observation. Three hundred seventy-six eligible patients were registered (with 4-year PFS of 34% and 4-year OS of 52%), and 194 eligible patients were randomized to continuous infusion intravenous IL-2 (9 million units/m(2)/day for 4 days followed 5 days later by 1.6 million units/m(2)/day for 10 days) versus observation. In randomized patients, there was no significant difference in PFS (hazard ratio of IL-2 to observation = 0.90; P =.56) or in OS (hazard ratio of IL-2 to observation = 0.88; P =.55). There were no deaths related to IL-2 treatment. Grade 4 IL-2-related toxicities (n = 14) were reversible. These results confirm earlier SWOG findings that cyclophosphamide, etoposide, TBI, and PBSCT can be administered to patients with relapsed/refractory NHL with encouraging PFS and OS. Posttransplantation IL-2 given at this dose and schedule of administration had no significant effect on PFS or OS. This study is registered at www.clinicaltrials.gov as NCT00002649.
Thompson
John A
JA
Puget Sound Oncology Consortium, Seattle, WA, USA. jat@u.washington.edu
Fisher
Richard I
RI
Leblanc
Michael
M
Forman
Stephen J
SJ
Press
Oliver W
OW
Unger
Joseph M
JM
Nademanee
Auayporn P
AP
Stiff
Patrick J
PJ
Petersdorf
Stephen H
SH
Fefer
Alexander
A
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000473:pathology; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
D000970:Antineoplastic Agents; D007376:Interleukin-2; D005047:Etoposide; D003520:Cyclophosphamide