title: Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496).
abstract: BACKGROUND
  In an ECOG-ACRIN Cancer Research Group study (E1496), maintenance rituximab (MR) was reported to prolong progression-free survival (PFS) in comparison with observation (OBS) alone in patients with indolent lymphoma after induction chemotherapy. Here the long-term follow-up of the same patient cohort is presented.
  
  
  METHODS
  Patients with indolent lymphoma received induction chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP). Patients with stable disease or a better response were then randomized to weekly rituximab (375 mg/m(2) × 4 doses) every 6 months for 2 years (MR) or to OBS. The primary endpoint was PFS; the secondary endpoints were overall survival (OS), response rate, and toxicities.
  
  
  RESULTS
  Of the 387 patients who initially received CVP induction, 158 were randomized to MR, and 153 were randomized to OBS. After a median follow-up of 11.5 years, patients on MR had longer median PFS (4.8 years) than patients on OBS (1.3 years; hazard ratio [HR], 0.49; P < .0001). However, there was no difference in OS between MR and OBS (10-year OS, 67% vs 59%; median OS, 13.5 years vs not reached; HR, 0.91; P = .69). Other than MR, only minimal residual disease after induction therapy was significantly associated with PFS on multivariate analysis (HR, 0.71; P = .02). A low initial tumor burden, minimal residual disease, follicular histology, a low Follicular Lymphoma International Prognostic Index score, and female sex were associated with longer OS. There was no increase in the rate of second primary malignancies with MR vs OBS.
  
  
  CONCLUSIONS
  With long-term follow-up, MR did not influence OS. The PFS benefit was maintained. MR should be considered optional for patients with indolent B-cell lymphoma. Cancer 2016;122:2996-3004. © 2016 American Cancer Society.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Barta
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Hailun
authors.initials: H
authors.lastname: Li
authors.affiliation: Yale University, New Haven, Connecticut.
authors.forename: Howard S
authors.initials: HS
authors.lastname: Hochster
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Fangxin
authors.initials: F
authors.lastname: Hong
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Edie
authors.initials: E
authors.lastname: Weller
authors.affiliation: British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Habermann
authors.affiliation: Northwestern University, Chicago, Illinois.
authors.forename: Leo I
authors.initials: LI
authors.lastname: Gordon
authors.affiliation: Palo Alto Medical Foundation, Palo Alto, California.
authors.forename: Natalia
authors.initials: N
authors.lastname: Colocci
authors.affiliation: Dartmouth Cancer Medical Center, Lebanon, New Hampshire.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Bengtson
authors.affiliation: Genentech, Inc, South San Francisco, California.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Horning
authors.affiliation: Washington University, St. Louis, Missouri. bkahl@wustl.edu.
authors.forename: Brad S
authors.initials: BS
authors.lastname: Kahl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000473:pathology; D060046:Maintenance Chemotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D012074:Remission Induction; D000069283:Rituximab / Q000008:administration & dosage; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000069283:Rituximab; D014750:Vincristine; D003520:Cyclophosphamide; D011241:Prednisone
keywords: follicular lymphoma; indolent lymphoma; non-Hodgkin lymphoma; rituximab; rituximab maintenance