Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial

Br J Haematol. 2014 Nov;167(3):327-36. doi: 10.1111/bjh.13036. Epub 2014 Jul 28.

Abstract

We conducted a multicentre, phase II study of interim positron emission tomography (PET) as a guide to risk-adapted therapy in high-risk patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Patients achieving negative fluorodeoxyglucose (FDG)-PET after three courses of R-MegaCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) received three additional courses, whereas PET-positive patients received two courses of R-IFE (rituximab, ifosfamide, etoposide) followed by BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous stem-cell transplantation. The primary endpoint was progression-free survival (PFS). 71 patients (median age 55 years, range 25-69) were enrolled. With a median follow-up of 42·8 months (range 7·2-58·4), the estimated 4-year PFS and overall survival (OS) were 67% and 78%, respectively, for the global series. Patients in complete remission after interim PET (N = 36) had significantly better 3-year PFS than those with partial response (N = 30) [81% vs. 57%, Hazard ratio (HR) = 2·6, 95% confidence interval (CI) = 1·02-6·65] but not a statistically significant longer OS. A retrospective PET central review was done for 51 patients. According to semiquantitative analysis, 3-year PFS (81% vs. 33%; HR = 6·9, 95% CI = 2·35-20·6) and OS (95% vs. 33%, HR = 19·4, 95% CI = 3·89-97·0) were significantly better for negative than for positive interim PET patients. Early PET assessment is valuable for risk stratification in DLBCL; for this purpose semiquantitative evaluation is a better predictor than visual criteria.

Keywords: autologous stem cell transplantation; fluorodeoxyglucose positron emission tomography; lymphoma.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carmustine / administration & dosage
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Cytarabine / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Etoposide / administration & dosage
  • Female
  • Fluorine Radioisotopes*
  • Fluorodeoxyglucose F18*
  • Humans
  • Ifosfamide / administration & dosage
  • Kaplan-Meier Estimate
  • Lymphoma, Large B-Cell, Diffuse / diagnostic imaging
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / therapy
  • Male
  • Melphalan / administration & dosage
  • Middle Aged
  • Peripheral Blood Stem Cell Transplantation
  • Positron-Emission Tomography*
  • Prednisone / administration & dosage
  • Prognosis
  • Prospective Studies
  • Radiopharmaceuticals*
  • Remission Induction
  • Rituximab
  • Transplantation, Autologous
  • Treatment Outcome
  • Vincristine / administration & dosage

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Cytarabine
  • Fluorodeoxyglucose F18
  • Rituximab
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Melphalan
  • Carmustine
  • Ifosfamide
  • Prednisone

Supplementary concepts

  • BEAM regimen