title: High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine.
abstract: OBJECTIVE
  To determine the response, failure-free survival (FFS), and overall survival rates and toxicity of rituximab plus an intense chemotherapy regimen in patients with previously untreated aggressive mantle-cell lymphoma (MCL).
  
  
  METHODS
  This was a prospective phase II trial of rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD; considered one cycle) alternating every 21 days with rituximab plus high-dose methotrexate-cytarabine (considered one cycle) for a total of six to eight cycles.
  
  
  RESULTS
  Of 97 assessable patients, 97% responded, and 87% achieved a complete response (CR) or unconfirmed CR. With a median follow-up time of 40 months, the 3-year FFS and overall survival rates were 64% and 82%, respectively, without a plateau in the curves. For the subgroup of patients < or = 65 years of age, the 3-year FFS rate was 73%. The principal toxicity was hematologic. Five patients died from acute toxicity. Four patients developed treatment-related myelodysplasia/acute myelogenous leukemia, and three patients died while in remission from MCL. A total of eight treatment-related deaths (8%) occurred.
  
  
  CONCLUSIONS
  Rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine is effective in untreated aggressive MCL. Toxicity is significant but expected. Because of the shorter FFS concurrent with significant toxicity in patients more than 65 years of age, this regimen is not recommended as standard therapy for this age subgroup. Larger prospective randomized studies are needed to define the role of this regimen in the treatment of MCL patients compared with existing and new treatment modalities.
authors.affiliation: Department of Lymphoma, Unit 429, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. jromague@mdanderson.org
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Romaguera
authors.forename: Luis
authors.initials: L
authors.lastname: Fayad
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rodriguez
authors.forename: Kristine R
authors.initials: KR
authors.lastname: Broglio
authors.forename: Frederick B
authors.initials: FB
authors.lastname: Hagemeister
authors.forename: Barbara
authors.initials: B
authors.lastname: Pro
authors.forename: Peter
authors.initials: P
authors.lastname: McLaughlin
authors.forename: Anas
authors.initials: A
authors.lastname: Younes
authors.forename: Felipe
authors.initials: F
authors.lastname: Samaniego
authors.forename: Andre
authors.initials: A
authors.lastname: Goy
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Sarris
authors.forename: Nam H
authors.initials: NH
authors.lastname: Dang
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.forename: Virginia
authors.initials: V
authors.lastname: Beasley
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Ruth L
authors.initials: RL
authors.lastname: Katz
authors.forename: Harish
authors.initials: H
authors.lastname: Gagneja
authors.forename: Barry I
authors.initials: BI
authors.lastname: Samuels
authors.forename: Terry L
authors.initials: TL
authors.lastname: Smith
authors.forename: Fernando F
authors.initials: FF
authors.lastname: Cabanillas
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide