High dose chemotherapy (HDCT) and hematopoietic stem cell transplantation (HPSCT) with subsequent immunotherapy in metastatic breast cancer (MBC): Final results of a phase I stud

Abstract

726 Introduction: This phase-I study prospectively analysed the efficacy and toxicity of HDCT, HPSCT and subsequent immunotherapy with T–cell reinfusion in chemotherapy-sensitive patients with MBC. Patients and methods: After leukapheresis and cryopreservation of T-cells, patients received 2 cycles of standard chemotherapy ET (epirubicin/paclitaxel) and 1 cycle of EI (epirubicin/ifosfamide) followed by G-CSF and stem cell harvest. After a third cycle of ET, responders (CR/PR) underwent HDCT (thiotepa 600 mg/m2/melphalan 140–180 mg/m2) and HPSCT. Once hematopoietic reconstitution was achieved, T-cells were reinfused followed by application of bispecific antibodies against HER-2/neu and EpCAM. Results: Thirty-three patients were recruited on study, and nineteen pts who had responded to initial standard chemotherapy (4 CR, 15 PR, OR = 58%) underwent HDCT and HPSCT. Subsequently, another 6 patients achieved a CR after HDCT resulting in an overall CR rate of 10/33 pts (30%). Two early deaths were observed (one toxic, one PD). T-cell reinfusion and bispecific antibodies were given to 17 patients. The main side effects during HDCT were severe (grade 3 / 4) hematotoxicity, mucositis, gastrointestinal toxicity. Elevated liver enzymes (grade 2 / 3) were seen in all patients. The intravenous application of bispecific antibodies resulted in intermittent fever and chills. Within a follow-up period of 54.7 to 79.1 months, all patients relapsed, and two patients are still alive. The median progression-free survival was 10.6 months (range: 2.1–31.2) and the median overall survival was 22.7 months (range: 1.8–79.1+). Conclusion: Despite a high complete remission rate and despite a novel immunotherapeutic approach including bispecific antibodies and T-cell reinfusion, HDCT and subsequent HPSCT failed to induce a major improvement of survival in chemosensitive patients with metastatic breast cancer. No significant financial relationships to disclose.