title: Combination of rituximab, bendamustine, and cytarabine for patients with mantle-cell non-Hodgkin lymphoma ineligible for intensive regimens or autologous transplantation.
abstract: OBJECTIVE
  The combination of bendamustine (B) and rituximab (R) is efficacious, with favorable toxicity in mantle-cell lymphoma (MCL). In this phase II study, we combined cytarabine with R and B (R-BAC) in patients with MCL age ≥ 65 years who were previously untreated or relapsed or refractory (R/R) after one prior immunochemotherapy treatment.
  
  
  METHODS
  In stage one, we established the maximum-tolerated dose (MTD) of cytarabine in R-BAC. In stage two, patients received R (375 mg/m(2) intravenously [IV] on day 1), B (70 mg/m(2) IV on days 2 and 3), and cytarabine (MTD IV on days 2 to 4) every 28 days for four to six cycles. The primary end point (overall response rate [ORR]) was evaluated by positron emission tomography. Secondary end points included safety, progression-free survival (PFS), response duration, and overall survival.
  
  
  RESULTS
  Forty patients (median age, 70 years; 20 previously untreated patients) were enrolled; 93% had Ann Arbor stage III/IV disease; 49% had high Mantle Cell International Prognostic Index scores, with 15% blastoid histology. All R/R patients (35% refractory) had previously received R-containing regimens. The cytarabine MTD used in stage two was 800 mg/m(2), and R-BAC was well tolerated, with an 85% treatment completion rate. The major toxicity was transient grades 3 to 4 thrombocytopenia (87% of patients); febrile neutropenia occurred in 12%. The ORR was 100% (95% complete response [CR]) for previously untreated and 80% (70% CR) for R/R patients. The 2-year PFS rate (± standard deviation) was 95% ± 5% for untreated and 70% ± 10% for R/R patients.
  
  
  CONCLUSIONS
  R-BAC is well tolerated and active against MCL.
authors: Department of Hematology, San Bortolo Hospital, Via Rodolfi 37, 36100 Vicenza, Italy.
authors: Carlo
authors: C
authors: Visco
authors: Silvia
authors: S
authors: Finotto
authors: Renato
authors: R
authors: Zambello
authors: Rossella
authors: R
authors: Paolini
authors: Andrea
authors: A
authors: Menin
authors: Roberta
authors: R
authors: Zanotti
authors: Francesco
authors: F
authors: Zaja
authors: Gianpietro
authors: G
authors: Semenzato
authors: Giovanni
authors: G
authors: Pizzolo
authors: Emanuele S G
authors: ES
authors: D'Amore
authors: Francesco
authors: F
authors: Rodeghiero
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007970:Leukopenia / Q000139:chemically induced; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage / Q000009:adverse effects; D049268:Positron-Emission Tomography; D012074:Remission Induction; D000069283:Rituximab; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D009588:Nitrogen Mustard Compounds; D003561:Cytarabine; D000069283:Rituximab; D000069461:Bendamustine Hydrochloride