Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era

J Clin Oncol. 2010 Sep 20;28(27):4184-90. doi: 10.1200/JCO.2010.28.1618. Epub 2010 Jul 26.

Abstract

Purpose: Salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT) is the standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL). Salvage regimens have never been compared; their efficacy in the rituximab era is unknown.

Patients and methods: Patients with CD20(+) DLBCL in first relapse or who were refractory after first-line therapy were randomly assigned to either rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) or rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP). Responding patients received high-dose chemotherapy and ASCT.

Results: The median age of the 396 patients enrolled (R-ICE, n = 202; R-DHAP, n = 194) was 55 years. Similar response rates were observed after three cycles of R-ICE (63.5%; 95% CI, 56% to 70%) and R-DHAP (62.8%; 95 CI, 55% to 69%). Factors affecting response rates (P < .001) were refractory disease/relapse less than versus more than 12 months after diagnosis (46% v 88%, respectively), International Prognostic Index (IPI) of more than 1 versus 0 to 1 (52% v 71%, respectively), and prior rituximab treatment versus no prior rituximab (51% v 83%, respectively). There was no significant difference between R-ICE and R-DHAP for 3-year event-free survival (EFS) or overall survival. Three-year EFS was affected by prior rituximab treatment versus no rituximab (21% v 47%, respectively), relapse less than versus more than 12 months after diagnosis (20% v 45%, respectively), and IPI of 2 to 3 versus 0 to 1 (18% v 40%, respectively). In the Cox model, these parameters were significant (P < .001).

Conclusion: In patients who experience relapse more than 12 months after diagnosis, prior rituximab treatment does not affect EFS. Patients with early relapses after rituximab-containing first-line therapy have a poor prognosis, with no difference between the effects of R-ICE and R-DHAP.

Trial registration: ClinicalTrials.gov NCT00137995.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20 / analysis
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Australia
  • Carboplatin / administration & dosage
  • Chemotherapy, Adjuvant
  • Cytarabine / administration & dosage
  • Dexamethasone / administration & dosage
  • Disease-Free Survival
  • Etoposide / administration & dosage
  • Europe
  • Female
  • Humans
  • Ifosfamide / administration & dosage
  • Israel
  • Kaplan-Meier Estimate
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / immunology
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Lymphoma, Large B-Cell, Diffuse / surgery*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • New York City
  • Proportional Hazards Models
  • Recurrence
  • Risk Assessment
  • Risk Factors
  • Rituximab
  • Salvage Therapy*
  • Stem Cell Transplantation*
  • Time Factors
  • Transplantation, Autologous
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Cytarabine
  • Rituximab
  • Etoposide
  • Dexamethasone
  • Carboplatin
  • Ifosfamide

Associated data

  • ClinicalTrials.gov/NCT00137995