A Multicenter Randomized Clinical Trial Evaluating Interleukin-2 Activated Hematopoietic Stem Cell Transplantation and Post-transplant IL-2 for High Risk Breast Cancer Patients

Summary Purpose. This Phase III randomized multicenter trial compared progression-free (PFS) and overall survival (OS) for autologous peripheral blood stem cell (aPBSC) transplantation with or without immunotherapy in high-risk breast cancer patients. Methods. Eligible patients had American Joint Committee on Cancer (AJCC) 5th Edition Stage II/IIIA with ≥ 4 axillary nodes, Stage IIIB, or chemotherapy-sensitive or stable Stage IV disease. Following treatment with cyclophosphamide, thiotepa and carboplatin (STAMP V), patients were randomized to aPBSC transplant with or without immunotherapy. Patients on immunotherapy received cells that were incubated in interleukin-2 (IL-2) for 24 h followed by parenteral IL-2 for 5 days then 2 days of rest for 4 weeks. Results. Fifty-nine patients were treated (35 Stage II/IIIA; 13 Stage IIIB; 11 Stage IV), 30 patients were randomized to immunotherapy and 29 patients to no immunotherapy. Neutrophils engrafted a median of 10 days post-transplant in both groups. The median times to platelet engraftment were 9 and 10 days after transplant in the no-immunotherapy and immunotherapy groups, respectively ( p = 0.03). There was no statistical evidence ( p = 0.61) of a difference in progression-free and surviving (PFS) at 3 years for patients receiving immunotherapy (53%) compared with no immunotherapy (48%). There was some evidence of superiority in overall survival (OS) at 3 years for patients receiving immunotherapy (83%) compared with no immunotherapy (69%), but the difference between survival curves was not statistically significant ( p = 0.08). Also, there was some evidence that patients developing acute graft versus host disease (aGVHD) had superior PFS ( p = 0.02) but not OS ( p = 0.19) than patients not developing aGVHD. Toxicities were transient and similar between groups, with no treatment-related deaths. Conclusions. This phase III study of high-risk breast cancer patients randomized to immunotherapy or no immunotherapy demonstrated that a well-tolerated immunotherapy regimen added to aPBSC transplant did not improve PFS, but there was some improvement in OS, but not by an amount that was statistically significant ( p = 0.08).