title: Autologous stem cell transplantation after conditioning with yttrium-90 ibritumomab tiuxetan plus BEAM in refractory non-Hodgkin diffuse large B-cell lymphoma: results of a prospective, multicenter, phase II clinical trial.
abstract: Lymphoma patients with persistent disease undergoing autologous transplantation have a very poor prognosis in the rituximab era. The addition of radioimmunotherapy to the conditioning regimen may improve the outcome for these patients. In a prospective, phase 2 study, we evaluated the safety and efficacy of the addition of (90)Y-ibritumomab tiuxetan to the conditioning chemotherapy in patients with refractory diffuse large B-cell lymphoma. Thirty patients with induction failure (primary refractory; n=18) or refractory to salvage immunochemotherapy at relapse (n=12) were included in the study. The median age of the patients was 53 years (range, 25-67). All patients were given (90)Y-ibritumomab tiuxetan at a fixed dose of 0.4 mCi/kg (maximum dose 32 mCi) 14 days prior to the preparative chemotherapy regimen. Histological examination showed that 22 patients had de novo diffuse large B-cell lymphoma and eight had transformed diffuse large B-cell lymphoma. All patients had persistent disease at the time of transplantation, with 25 patients considered to be chemorefractory. The median time to neutrophil recovery (>500 white blood cells/μL) was 11 days (range, 9-21), while the median time to platelet recovery (>20,000 platelets/μL) was 13 days (range, 11-35). The overall response rate at day +100 was 70% (95% CI, 53.6-86.4) with 60% (95% CI, 42.5-77.5) of patients obtaining a complete response. After a median follow-up of 31 months for alive patients (range, 16-54), the estimated 3-year overall and progression-free survival rates are 63% (95% CI, 48-82) and 61% (95% CI, 45-80), respectively. We conclude that autologous transplantation with conditioning including (90)Y-ibritumomab tiuxetan is safe and results in a very high response rate with promising survival in this group of patients with refractory diffuse large B-cell lymphoma with a very poor prognosis. Study registered at European Union Drug Regulating Authorities Clinical Trials (EudraCT) N. 2007-003198-22.
authors.affiliation: jbriones@santpau.cat.
authors.forename: Javier
authors.initials: J
authors.lastname: Briones
authors.forename: Silvana
authors.initials: S
authors.lastname: Novelli
authors.forename: José A
authors.initials: JA
authors.lastname: García-Marco
authors.forename: José F
authors.initials: JF
authors.lastname: Tomás
authors.forename: Teresa
authors.initials: T
authors.lastname: Bernal
authors.forename: Carlos
authors.initials: C
authors.lastname: Grande
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Canales
authors.forename: Antonio
authors.initials: A
authors.lastname: Torres
authors.forename: José M
authors.initials: JM
authors.lastname: Moraleda
authors.forename: Carlos
authors.initials: C
authors.lastname: Panizo
authors.forename: Isidro
authors.initials: I
authors.lastname: Jarque
authors.forename: Francisca
authors.initials: F
authors.lastname: Palmero
authors.forename: Miguel
authors.initials: M
authors.lastname: Hernández
authors.forename: Eva
authors.initials: E
authors.lastname: González-Barca
authors.forename: Dulce
authors.initials: D
authors.lastname: López
authors.forename: Dolores
authors.initials: D
authors.lastname: Caballero
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002330:Carmustine; D003561:Cytarabine; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D008297:Male; D008558:Melphalan; D008875:Middle Aged; D009367:Neoplasm Staging; D011034:Podophyllotoxin; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D003561:Cytarabine; C422802:ibritumomab tiuxetan; D011034:Podophyllotoxin; D008558:Melphalan; D002330:Carmustine