Response to Rituximab Induction Is a Predictive Marker in B-Cell Post-Transplant Lymphoproliferative Disorder and Allows Successful Stratification Into Rituximab or R-CHOP Consolidation in an International, Prospective, Multicenter Phase II Trial - Archive ouverte HAL Access content directly
Journal Articles Journal of Clinical Oncology Year : 2017

Response to Rituximab Induction Is a Predictive Marker in B-Cell Post-Transplant Lymphoproliferative Disorder and Allows Successful Stratification Into Rituximab or R-CHOP Consolidation in an International, Prospective, Multicenter Phase II Trial

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Ralf U. Trappe
  • Function : Author
Daan Dierickx
  • Function : Author
Heiner Zimmermann
  • Function : Author
Peter Mollee
  • Function : Author
Jan M. Zaucha
  • Function : Author
Martin H. Dreyling
  • Function : Author
Petra Reinke
  • Function : Author
Gregor Verhoef
  • Function : Author
Marion Subklewe
  • Function : Author
Andreas Hüttmann
  • Function : Author
Thomas Tousseyn
  • Function : Author
Gilles Salles
Volker Kliem
  • Function : Author
Ingeborg A. Hauser
  • Function : Author
Corrado Tarella
  • Function : Author
Eric van den Neste
  • Function : Author
Olivier Gheysens
  • Function : Author
Hanno Riess
  • Function : Author

Abstract

Purpose The Sequential Treatment of CD20-Positive Posttransplant Lymphoproliferative Disorder (PTLD-1) trial ( ClinicalTrials.gov identifier, NCT01458548) established sequential treatment with four cycles of rituximab followed by four cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy as a standard in the management of post-transplant lymphoproliferative disorder (PTLD) and identified response to rituximab induction as a prognostic factor for overall survival. We hypothesized that rituximab consolidation might be sufficient treatment for patients with a complete response after rituximab induction. Patients and Methods In this prospective, international, multicenter phase II trial, 152 treatment-naive adult solid organ transplant recipients, with CD20+ PTLD unresponsive to immunosuppression reduction, were treated with four weekly doses of rituximab induction. After restaging, complete responders continued with four courses of rituximab consolidation every 21 days; all others received four courses of rituximab plus CHOP chemotherapy every 21 days. The primary end point was treatment efficacy measured as the response rate in patients who completed therapy and the response duration in those who completed therapy and responded. Secondary end points were frequency of infections, treatment-related mortality, and overall survival in the intention-to-treat population. Results One hundred eleven of 126 patients had a complete or partial response (88%; 95% CI, 81% to 93%), of whom 88 had a complete response (70%; 95% CI, 61% to 77%). Median response duration was not reached. The 3-year estimate was 82% (95% CI, 74% to 90%). Median overall survival was 6.6 years (95% CI, 5.5 to 7.6 years). The frequency of grade 3 or 4 infections and of treatment-related mortality was 34% (95% CI, 27% to 42%) and 8% (95% CI, 5% to 14%), respectively. Response to rituximab induction remained a prognostic factor for overall survival despite treatment stratification. Conclusion In B-cell PTLD, treatment stratification into rituximab or rituximab plus CHOP consolidation on the basis of response to rituximab induction is feasible, safe, and effective

Dates and versions

hal-01796181 , version 1 (19-05-2018)

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Ralf U. Trappe, Daan Dierickx, Heiner Zimmermann, Franck Morschhauser, Peter Mollee, et al.. Response to Rituximab Induction Is a Predictive Marker in B-Cell Post-Transplant Lymphoproliferative Disorder and Allows Successful Stratification Into Rituximab or R-CHOP Consolidation in an International, Prospective, Multicenter Phase II Trial. Journal of Clinical Oncology, 2017, 35 (5), pp.536-543. ⟨10.1200/JCO.2016.69.3564⟩. ⟨hal-01796181⟩
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