Y90-Ibritumomab tiuxetan (Y90-IT) and high-dose melphalan as conditioning regimen before autologous stem cell transplantation for elderly patients with lymphoma in relapse or resistant to chemotherapy: a feasibility trial (SAKK 37/05).
Standard conditioning regimens for autologous stem cell transplantation (ASCT) are often not tolerated by elderly patients, on one hand. Single high-dose melphalan, on the other hand, has been shown to be safe and active as a pretransplant preparative regimen in elderly patients. Y90-Ibritumomab tiuxetan (Y90-IT) is well tolerated and feasible in the transplantation setting. We therefore investigated the combination of high-dose melphalan and Y90-IT as a conditioning regimen for patients ≥65 years of age. Patients with relapsed or resistant CD20-positive lymphoma in remission after salvage chemotherapy could be enrolled. High-dose therapy consisted of standard dose Y90-IT (0.4-mCi/kg body weight) followed by melphalan at escalating doses (100, 140, 170 and 200 mg/m2) and ASCT. The primary objective was to identify the maximum tolerated dose; secondary end points were complete response (CR) rate 100 days after transplantation and toxicity. Twenty patients (median age 72 years) were included. No DLT occurred at any dose level. Thirteen patients completed the treatment, 11 were evaluable for response. Seven patients did not complete treatment because of mobilization failure (n = 3), progressive disease (n = 2), worsening of cardiac function (n = 1), and grade 3 dyspnea (n = 1). Seven patients achieved a CR/complete remission/unconfirmed (CRu) and 2 had stable disease. Five out of 7 responding patients were still alive more than 3 years after transplantation. The 2 patients with SD had a long-term survival of 3 and 5 years, respectively. Nonhematological grade 3 or higher treatment related adverse events (AEs) were infection (n = 6), including 2 cases of febrile neutropenia, diarrhea (n = 3), mucositis, anorexia, viral hepatitis, hypokalemia, dehydration, and multiorgan failure (n = 1 for each). The combination of Y90-IT and high-dose melphalan is feasible before ASCT for elderly patients, with promising activity and manageable toxicity.
Medizinische Universitätsklinik, Liestal, Switzerland.
Michèle
M
Voegeli
SAKK Coordinating Center, Bern, Switzerland.
Stephanie
S
Rondeau
SAKK Coordinating Center, Bern, Switzerland.
Simona
S
Berardi Vilei
Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland.
Erika
E
Lerch
Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland.
Luciano
L
Wannesson
Inselspital Bern, Bern, Switzerland.
Thomas
T
Pabst
Universitätsspital Basel, Basel, Switzerland.|Ortenau Klinikum Offenburg, Offenburg, Germany.
Jochen
J
Rentschler
Kantonsspital Aarau, Aarau, Switzerland.
Mario
M
Bargetzi
Kantonsspital Bruderholz, Bruderholz, Switzerland.
Lorenz
L
Jost
CHUV, Lausanne, Switzerland.|Hirslanden Lausanne SA, Lausanne, Switzerland.
Nicolas
N
Ketterer
CHUV, Lausanne, Switzerland.
Angelika
A
Bischof Delaloye
Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland.
Michele
M
Ghielmini
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008223:Lymphoma / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D060787:Neoplasm Grading; D012008:Recurrence; D019233:Retreatment; D013997:Time Factors; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes
D000911:Antibodies, Monoclonal; D015021:Yttrium Radioisotopes; C422802:ibritumomab tiuxetan; D008558:Melphalan
Y90-Ibritumomab tiuxetan; autologous stem cell transplantation; high-dose melphalan; recurrent lymphoma