Immunotherapy with rituximab/interleukin-2 after autologous stem cell transplantation as treatment for CD20+ non-Hodgkin's lymphoma.
BACKGROUND
Relapse of non-Hodgkin's lymphoma (NHL) remains a problem after autologous stem cell transplantation (ASCT). Soon after ASCT, the immune system is not very active, and this immune incompetence could thus result in decreased ability for immune-mediated tumor eradication. The early addition of immunotherapy after ASCT might decrease the incidence of relapse and prolong survival. In an initial phase I/II trial at our center, the immune modulator interleukin-2 (IL-2) increased over baseline natural killer and lymphokine-activated killer activity in vitro. Because rituximab can lyse CD20-bearing cells by antibody-dependent cellular cytotoxicity, adding IL-2 to rituximab might boost its effectiveness. It thus seemed reasonable to study this combination after ASCT. The results of our phase II study are reported herein.


METHODS
Twenty patients with CD20+ NHL who had ASCT were treated. The median time to starting therapy was 79 days (range, 49-100 days) after transplantation.


RESULTS
The majority of patients reported grade <or= 2 erythema, induration and pain at IL-2 injection sites, flu-like symptoms, and worsening fatigue. Neutropenia that responded to granulocyte colony-stimulating factor was the most common grade 3/4 toxicity, seen in 45% of patients. There were no treatment-related deaths. Eighteen of 20 patients remain alive in complete remission, with a median follow-up of 55.5 months (range, 17-64 months).


CONCLUSIONS
Interleukin-2/rituximab can be administered after ASCT with manageable toxicity. A randomized trial is under way to address whether this combination therapy is beneficial to patients with NHL who have had ASCT.
Holmberg
Leona A
LA
Clinical Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. lholmber@fhcrc.org
Maloney
David
D
Bensinger
William
W
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000069283:Rituximab; D033581:Stem Cell Transplantation; D015996:Survival Rate; D014182:Transplantation, Autologous
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D007376:Interleukin-2; D000069283:Rituximab