Improved outcome of patients with relapsed/refractory Hodgkin lymphoma with a new fotemustine-based high-dose chemotherapy regimen

Br J Haematol. 2016 Jan;172(1):111-21. doi: 10.1111/bjh.13803. Epub 2015 Oct 12.

Abstract

High-dose chemotherapy (HDT) with autologous stem cell transplantation is the standard of care for relapsed/refractory (RR) Hodgkin lymphoma (HL). Given that HDT may cure a sizeable proportion of patients refractory to first salvage, development of newer conditioning regimens remains a priority. We present the results of a novel HDT regimen in which carmustine was substituted by a third-generation chloroethylnitrosourea, fotemustine, with improved pharmacokinetics and safety (FEAM; fotemustine, etoposide, cytarabine, melphalan) in 122 patients with RR-HL accrued into a prospective registry-based study. Application of FEAM resulted in a 2-year progression-free survival (PFS) of 73·8% [95% confidence interval (CI), 0·64-0·81] with median PFS, overall survival and time to progression yet to be reached. The 2-year risk of progression adjusted for the competitive risk of death was 19·4% (95% CI, 0·12-0·27) for the entire patient population. Most previously established independent risk factors, except for fluorodeoxyglucose ((18) (F) FDG)-uptake, were unable to predict for disease progression and survival after FEAM. Although 32% of patients had (18) (F) FDG-positrin emission tomography-positive lesions before HDT, the 2-year risk of progression adjusted for competitive risk of death was 19·4% (95% CI; 0·12-0·27). No unusual acute toxicities or early/late pulmonary adverse events were registered. FEAM emerges as an ideal HDT regimen for RR-HL patients typically pre-exposed to lung-damaging treatments.

Keywords: Hodgkin lymphoma; autologous stem cell transplantation; fotemustine; high-dose chemotherapy.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Child
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Drug Evaluation / methods
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Female
  • Graft Survival
  • Hematopoietic Stem Cell Transplantation / methods
  • Hodgkin Disease / diagnostic imaging
  • Hodgkin Disease / drug therapy*
  • Hodgkin Disease / therapy
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Melphalan / administration & dosage
  • Melphalan / adverse effects
  • Middle Aged
  • Nitrosourea Compounds / administration & dosage
  • Nitrosourea Compounds / adverse effects
  • Organophosphorus Compounds / administration & dosage
  • Organophosphorus Compounds / adverse effects
  • Positron-Emission Tomography
  • Prospective Studies
  • Registries
  • Salvage Therapy / adverse effects
  • Salvage Therapy / methods
  • Transplantation Conditioning / methods
  • Treatment Outcome
  • Young Adult

Substances

  • Nitrosourea Compounds
  • Organophosphorus Compounds
  • Cytarabine
  • Etoposide
  • fotemustine
  • Melphalan