title: Phase II study of immunomodulation with granulocyte-macrophage colony-stimulating factor, interleukin-2, and rituximab following autologous stem cell transplant in patients with relapsed or refractory lymphomas.
abstract: High-dose chemotherapy followed by autologous stem cell transplant (ASCT) leads to durable remissions in approximately half of patients with chemosensitive relapsed or refractory aggressive lymphomas; however, many will relapse despite ASCT secondary to persistent minimal residual disease (MRD) or malignant graft contamination. Post-transplant rituximab may eradicate MRD. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) might enhance the efficacy of rituximab by augmenting antibody-dependent cellular cytotoxicity (ADCC). We hypothesized that given together, rituximab, GM-CSF, and IL-2 might eradicate MRD and improve event-free survival following ASCT. Forty-six patients with relapsed non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) were enrolled. Stem cells were mobilized with G-CSF and GM-CSF following chemotherapy. Following BEAM conditioning, patients received GM-CSF until neutrophil engraftment. Between days + 30 and + 120, patients received one dose of rituximab 375 mg/m(2) (cycle 1), followed by three cycles of GM-CSF 250 microg/m(2)/day SQ days 1-5, IL-2 1.5 x 10(6) IU/m(2)/day SQ days 6-12, and rituximab 375 mg/m(2) IV day 9, repeated every 21 days. Thirty-eight patients were eligible for post-ASCT immunotherapy. Nine patients completed 1-2 cycles and 21 completed 3-4 cycles; eight patients did not receive post-ASCT immunotherapy. Grade 3-4 neutropenia and grade 3 thrombocytopenia were observed. With a median follow-up of 30 months, the estimated 5-year OS and EFS for all patients eligible for immunotherapy are 65% and 45%, respectively. Post-ASCT immunomodulation with rituximab, IL-2, and GM-CSF was feasible and safe, but not all patients were able to continue on to post-ASCT immunotherapy.
authors.affiliation: Department of Medicine, University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Xavier
authors.initials: X
authors.lastname: Poiré
authors.forename: Justin
authors.initials: J
authors.lastname: Kline
authors.forename: David
authors.initials: D
authors.lastname: Grinblatt
authors.forename: Todd
authors.initials: T
authors.lastname: Zimmerman
authors.forename: Kathy
authors.initials: K
authors.lastname: Conner
authors.forename: Carolyn
authors.initials: C
authors.lastname: Muhs
authors.forename: Thomas
authors.initials: T
authors.lastname: Gajewski
authors.forename: Koen
authors.initials: K
authors.lastname: Van Besien
authors.forename: Sonali M
authors.initials: SM
authors.lastname: Smith
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D056747:Immunomodulation; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000069283:Rituximab; D016879:Salvage Therapy; D015996:Survival Rate; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007376:Interleukin-2; D000069283:Rituximab; D016178:Granulocyte-Macrophage Colony-Stimulating Factor