title: First-line treatment with rituximab-hyperCVAD alternating with rituximab-methotrexate-cytarabine and followed by consolidation with 90Y-ibritumomab-tiuxetan in patients with mantle cell lymphoma. Results of a multicenter, phase 2 pilot trial from the GELTAMO group.
abstract: The prognosis for fit patients with mantle cell lymphoma has improved with intensive strategies. Currently, the role of maintenance/consolidation approaches is being tested as relapses continue to appear. In this trial we evaluated the feasibility, safety and efficacy of rituximab-hyperCVAD alternating with rituximab-methotrexate-cytarabine followed by consolidation with (90)Y-ibritumomab tiuxetan. Patients received six cycles followed by a single dose of (90)Y-ibritumomab tiuxetan. Thirty patients were enrolled; their median age was 59 years. Twenty-four patients finished the induction treatment, 23 achieved complete remission (77%, 95% confidence interval 60-93) and one patient had progressive disease (3%). Eighteen patients (60%), all in complete remission, received consolidation therapy. In the intent-to-treat population, failure-free, progression-free and overall survival rates at 4 years were 40% (95% confidence interval 20.4-59.6), 52% (95% confidence interval 32.4-71.6) and 81% (95% confidence interval 67.28-94.72), respectively. For patients who received consolidation, failure-free and overall survival rates were 55% (95% confidence interval 31.48-78.52) and 87% (95% confidence interval 70-100), respectively. Hematologic toxicity was significant during induction and responsible for one death (3.3%). After consolidation, grade 3-4 neutropenia and thrombocytopenia were observed in 72% and 83% of patients, with a median duration of 5 and 12 weeks, respectively. Six (20%) patients died, three due to secondary malignancies (myelodysplastic syndrome and bladder and rectum carcinomas). In conclusion, in our experience, rituximab-hyperCVAD alternated with rituximab-methotrexate-cytarabine and followed by consolidation with (90)Y-ibritumomab tiuxetan was efficacious although less feasible than expected. The unacceptable toxicity observed, especially secondary malignancies, advise against the use of this strategy.
  
  
  BACKGROUND
  clinical.gov identifier: NCT2005-004400-37.
authors.affiliation: rarranzs@telefonica.net.
authors.forename: Reyes
authors.initials: R
authors.lastname: Arranz
authors.forename: Ana
authors.initials: A
authors.lastname: García-Noblejas
authors.forename: Carlos
authors.initials: C
authors.lastname: Grande
authors.forename: Jimena
authors.initials: J
authors.lastname: Cannata-Ortiz
authors.forename: José J
authors.initials: JJ
authors.lastname: Sánchez
authors.forename: José-Antonio
authors.initials: JA
authors.lastname: García-Marco
authors.forename: Concepción
authors.initials: C
authors.lastname: Aláez
authors.forename: Javier
authors.initials: J
authors.lastname: Pérez-Calvo
authors.forename: Pilar
authors.initials: P
authors.lastname: Martínez-Sánchez
authors.forename: Blanca
authors.initials: B
authors.lastname: Sánchez-González
authors.forename: Miguel-Angel
authors.initials: MA
authors.lastname: Canales
authors.forename: Eulogio
authors.initials: E
authors.lastname: Conde
authors.forename: Alejandro
authors.initials: A
authors.lastname: Martín
authors.forename: Eva
authors.initials: E
authors.lastname: Arranz
authors.forename: María-José
authors.initials: MJ
authors.lastname: Terol
authors.forename: Antonio
authors.initials: A
authors.lastname: Salar
authors.forename: Dolores
authors.initials: D
authors.lastname: Caballero
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D003561:Cytarabine; D000069283:Rituximab; C422802:ibritumomab tiuxetan; D008727:Methotrexate