title: Phase II study of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone immunochemotherapy followed by yttrium-90-ibritumomab tiuxetan in untreated mantle-cell lymphoma: Eastern Cooperative Oncology Group Study E1499.
abstract: OBJECTIVE
  To test the hypothesis that consolidation therapy with yttrium-90 ((90)Y) -ibritumomab tiuxetan after brief initial therapy with four cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated mantle-cell lymphoma would be a well-tolerated regimen that would improve outcomes compared with historical R-CHOP data.
  
  
  METHODS
  Patients ≥ 18 years old with histologically confirmed mantle-cell lymphoma expressing CD20 and cyclin D1 who had not received any previous therapy and had an Eastern Cooperative Oncology Group performance status of 0 to 2 and adequate organ function were eligible. The study enrolled and treated 57 patients, of whom 56 patients were eligible. Fifty-two patients (50 eligible patients) received (90)Y-ibritumomab tiuxetan. The study design required 52 eligible patients to detect a 50% improvement in the median time to treatment failure (TTF) compared with that reported for six cycles of R-CHOP.
  
  
  RESULTS
  With 56 analyzed patients (median age, 60 years; men, 73%), the overall response rate was 82% (55% complete response/complete response-unconfirmed). With a median follow-up of 72 months, the median TTF was 34.2 months. The median overall survival (OS) has not been reached, with an estimated 5-year OS of 73% (79% for patients ≤ age 65 years v 62% for patients > age 65 years; P = .08 [log-rank test]). There were no unexpected toxicities.
  
  
  CONCLUSIONS
  R-CHOP given for four cycles followed by (90)Y-ibritumomab tiuxetan compared favorably with historical results with six cycles of R-CHOP in patients with previously untreated mantle-cell lymphoma. This regimen was well tolerated and should be applicable to most patients with this disease.
authors.affiliation: Lymphoma Service, Fox Chase Cancer Center, Room C307, 333 Cottman Ave, Philadelphia, PA 19111, USA. m_smith@fccc.edu
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: Smith
authors.forename: Hailun
authors.initials: H
authors.lastname: Li
authors.forename: Leo
authors.initials: L
authors.lastname: Gordon
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Paietta
authors.forename: Andres
authors.initials: A
authors.lastname: Forero-Torres
authors.forename: Brad S
authors.initials: BS
authors.lastname: Kahl
authors.forename: Ranjana
authors.initials: R
authors.lastname: Advani
authors.forename: Fangxin
authors.initials: F
authors.lastname: Hong
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Horning
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D020522:Lymphoma, Mantle-Cell / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D016499:Radioimmunotherapy / Q000009:adverse effects; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use*; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D019275:Radiopharmaceuticals; D000069283:Rituximab; C422802:ibritumomab tiuxetan; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone