1004PD - Follicular lymphoma: clinical and mollecular characteristics of histologic transformation

Date 11 September 2017
Event ESMO 2017 Congress
Session Haematological malignancies
Topics Lymphomas
Haematologic Malignancies
Presenter Miriam Mendez Garcia
Citation Annals of Oncology (2017) 28 (suppl_5): v355-v371. 10.1093/annonc/mdx373
Authors M. Mendez Garcia1, M. Sánchez-Beato Gomez1, J. González Rincón1, J. Gomez Codina2, M. Llanos Rodríguez3, A. Rueda Domínguez4, C. Quero Blanco5, L. De la Cruz Merino6, J. Gumá Padró7, M. Provencio Pulla8
  • 1Medical Oncology, Hospital University Puerta de Hierro, 28222 - Majadahonda/ES
  • 2Medical Oncology, Hospital Universitari i Politècnic La Fe, 46026 - Valencia/ES
  • 3Medical Oncology, Hospital University of Canarias, 38320 - Santa Cruz de Tenerife/ES
  • 4Oncology, Costa del Sol Hospital, Marbella/ES
  • 5Medical Oncology, Hospital Universitary Virgen de la Victoria Málaga, 29010 - Malaga/ES
  • 6Medical Oncology, Hospital University Virgen Macarena Sevilla, 41009 - Sevilla/ES
  • 7Medical Oncology, Hospital Universitari Sant Joan de Reus, 43204 - Reus/ES
  • 8Servicio De Oncología Médica, Hospital Universitario Puerta de Hierro, 28222 - Madrid/ES

Abstract

Background

Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma (NHL). Histological transformation (HT) refers to the evolution of a clinically indolent NHL to an aggressive one. The rates of HT in published series range from 10% to 60%. There are no specific clinical characteristics that can predict transformation. Some molecular parameters associated with transformation are: p53 expression, expression of c-MYC, BCL-6 mutations. This suggests that multiple alternative mechanisms are likely to be involved in the pathogenesis of HT.

Methods

We report a prospective, multicenter (39 Spanish member institutions of Grupo Oncológico para Tratamiento de Linfomas-GOTEL-), observational study designed to collect data on disease presentation, treatment and clinical outcomes of HT. Inclusion criteria for this analysis were initial diagnosis of grade 1-3a FL and enrolment from 1990 to 2016. HT was defined as refractory/recurrent disease with clinical or pathologic diagnosis. Whole exome sequencing of the HT samples has been performed and compared with samples from patients with LF without transformation.

Results

Of the 975 evaluable patients, 64 had HT. Characteristics associated with an increased risk of HT were: the presence of B symptoms (p = 0.001), increased LDH (p = 0.02), high Follicular Lymphoma International Prognostic Index (FLIPI) (p = 0.01) and poor perfomance status (p = 0.01). In this group of patients, the cumulative incidence rate of HT at 5 years was 7.3%; the rate of HT remained constant, reaching a plateau after 14 years. Expectant management also predicted for a higher risk of HT (p = 0.0001). The median survival from transformation was 5 years. Regarding molecular characteristics, we found that all patients with HT had more than 4 mutations at diagnosis of FL in a group of 14 genes that are frequently mutated in patients with HT: CSMD3, DTX1, FOXO1, LRP1B, NOTCH2, PIM1, POU2F2, ATM, BCL7A, HIST1H1E, IRF8, PCLO, EZH2 and TNFAIP3.

Conclusions

There are clinical (increased LDH, B symptoms, high FLIPI, poor performance status) and molecular factors (more than 4 mutations in specific genes) at diagnosis correlate with an increased risk of HT. These predictors of HT could help to develop targeted therapies to prevent HT in high risk patients or improve current salvage approaches.

Clinical trial identification

GOTEL trial of histological transformation

Legal entity responsible for the study

GOTEL (Grupo Oncológico para el Tratamiento y Estudio de Linfomas)

Funding

None

Disclosure

All authors have declared no conflicts of interest.