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

• Published in: Leukemia & lymphoma 2010-07, Vol.51 (7), p.1241-1250
• Main Authors: Poiré, Xavier, Kline, Justin, Grinblatt, David, Zimmerman, Todd, Conner, Kathy, Muhs, Carolyn, Gajewski, Thomas, Van Besien, Koen, Smith, Sonali M.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Combined Modality Therapy; Drug Resistance, Neoplasm; Drug Therapy, Combination; Female; GM-CSF; Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hodgkin Disease - immunology; Hodgkin Disease - pathology; Hodgkin Disease - therapy; Humans; IL-2; Immunomodulation; Immunotherapy; Interleukin-2 - administration & dosage; Lymphoma, Non-Hodgkin - immunology; Lymphoma, Non-Hodgkin - pathology; Lymphoma, Non-Hodgkin - therapy; Male; Middle Aged; Neoplasm Staging; Post-transplant immunotherapy; Relapsed and refractory lymphoma; Rituximab; Salvage Therapy; Survival Rate; Transplantation, Autologous; Treatment Outcome; Young Adult
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428194.2010.486876

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/m2 (cycle 1), followed by three cycles of GM-CSF 250  μg/m2/day SQ days 1-5, IL-2 1.5 × 106 IU/m2/day SQ days 6-12, and rituximab 375 mg/m2 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.