Y90-ibritumomab tiuxetan (Y90-IT) and high-dose melphalan as conditioning regimen before autologous stem cell transplantation (ASCT) for elderly patients with lymphoma in relapse or resistant to chemotherapy: A feasibility trial (SAKK 37/05).

Abstract

8560 Background: Standard conditioning regimens for ASCT are often not tolerated by elderly patients. Single agent high-dose melphalan has been shown to be safe and active in elderly patients with multiple myeloma. Y90-IT is a well-tolerated lymphoma treatment and feasible in the transplantation setting. We therefore investigated this combination of high-dose melphalan and Y90-IT as a conditioning regimen for elderly patients. Methods: Patients ≥65 years with relapsed or chemotherapy resistant CD20-positive lymphoma in PR or CR after salvage chemotherapy could be enrolled prior to stem cell mobilization. Myeloablation regimen consisted of standard dose Y90-IT followed by melphalan at escalating doses (100, 140, 170 and 200mg/m2, with a 3+3 phase I design) and by ASCT. The primary objective was to identify the MTD of melphalan in combination with standard dose Y90-IT (as defined < 1 DLT in 3 patients); secondary endpoints were toxicity and CR rate 100 days after transplantation. Results: Between 2006-2012 twenty patients were included. Median age was 72 years (range 66-77). One patient was considered retrospectively ineligible and was evaluable for toxicity but not for DLT. Thirteen patients received the treatment and were transplanted. Eleven patients were evaluable for DLT. No DLT occurred. Non-hematological grade 3 or higher treatment related adverse events were: infection (n=6, including 2 cases of febrile neutropenia), diarrhea (n=3), mucositis, anorexia, viral hepatitis, hypokalemia, dehydration and multi-organ failure (n=1). Seven patients did not start treatment because of mobilization failure (n=3), progressive disease (n=2), worsening of cardiac failure (n=1) and grade 3 dyspnea (n=1). Seven patients achieved a CR/CRu and 2 patients were stable 100 days after transplantation. Conclusions: The combination ofstandard dose Y90-IT and high dose melphalan (200mg/m2) is a safe and feasible conditioning regimen before ASCT for patients ≥65 years. The results show promising activity. Clinical trial information: NCT00392691.