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/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.
Declaration of interest: Xavier Poiré is supported by a Franqui-De Roover grant (Salus Sanguinis Foundation), Brussels, Belgium. Koen van Besien is supported by NCI K24CA116471. Justin Kline is supported by NCI K23CA133196. The study was supported by a grant from Bayer Healthcare Pharmaceuticals.