A single-institution retrospective cohort study of first-line R-EPOCH chemoimmunotherapy for Richter syndrome demonstrating complex chronic lymphocytic leukaemia karyotype as an adverse prognostic factor

Br J Haematol. 2018 Jan;180(2):259-266. doi: 10.1111/bjh.15035. Epub 2017 Nov 28.

Abstract

Richter Syndrome, an aggressive lymphoma occurring in patients with chronic lymphocytic leukaemia (CLL), has a generally poor prognosis and anthracycline-based chemoimmunotherapy regimens designed to treat de novo diffuse large B-cell lymphoma achieve modest clinical benefit. R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) has demonstrated greater activity against aggressive B-cell histologies but has not been studied in Richter Syndrome. We conducted a retrospective cohort study of 46 Richter Syndrome patients treated with first-line R-EPOCH at our institution between 1 January 2006 and 31 May 2014. The median progression-free survival (PFS) was 3·5 months [95% confidence interval (CI): 2·0-7·6] and median overall survival (OS) was 5·9 months (95% CI: 3·2-10·3). Toxicity was high and 30% of patients died without progression or response. Patients with a complex CLL karyotype had significantly shorter PFS and OS (P = 0·005 and P = 0·002, respectively). Multivariable analysis identified complex CLL karyotype as the most significant predictor of decreased survival [Hazard ratio (HR) 2·72, 95% CI: 1·14-6·52, P = 0·025], adjusting for number of prior CLL treatments (P = 0·036). Richter Syndrome patients with complex CLL karyotype experience poor survival with R-EPOCH treatment and novel approaches are needed for these patients. In contrast, survival of patients without a complex CLL karyotype was similar to patients with de novo diffuse large B-cell lymphoma.

Keywords: Richter syndrome; chemotherapy; chronic lymphocytic leukaemia (CLL).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use
  • Disease Progression
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use
  • Etoposide / adverse effects
  • Etoposide / therapeutic use
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Karyotype
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / mortality
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
  • Male
  • Middle Aged
  • Prednisone / adverse effects
  • Prednisone / therapeutic use
  • Prognosis
  • Retrospective Studies
  • Rituximab / administration & dosage
  • Treatment Outcome
  • Vincristine / adverse effects
  • Vincristine / therapeutic use

Substances

  • Biomarkers, Tumor
  • Rituximab
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • EPOCH protocol