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PKP-029 Pharmacogenetic study of the influence of polymorphisms in the tnfr1a and fas genes on the response to rituximab and chemotherapy in follicular lymphoma patients
  1. MDR Gutiérrez Cívicos1,
  2. P Conesa Zamora2,
  3. I Español Morales3,
  4. D Gutiérrez-Meca Maestre3,
  5. AC Viney1,
  6. I Muñoz García1,
  7. MH García Lagunar1,
  8. A García Márquez1,
  9. R Guerrero Bautista1,
  10. E Ferris Villanueva1
  1. 1Hospital General Universitario Santa Lucía, Pharmacy, Cartagena, Spain
  2. 2Hospital General Universitario Santa Lucía, Molecular Pathology and Pharmacogenetics, Cartagena, Spain
  3. 3Hospital General Universitario Santa Lucía, Hematology, Cartagena, Spain

Abstract

Background Interindividual variability in treatment response may be associated with the presence of gene polymorphisms. Monoclonal antibodies seem to exert, at least partly, their mechanism of action by inducing apoptosis in antigen expressing cells. TNFR1A and FAS are receptors involved in the induction of apoptosis by the extrinsic pathway. Polymorphisms in these genes may be implicated in the response to rituximab, a monoclonal antibody targeting neoplastic B cells expressing CD20 antigen.

Purpose To assess the influence of the functional gene polymorphisms rs767455 TNFR1A and rs1800682 FAS on response to treatment with rituximab associated with the chemotherapy CHOP (cyclophosphamide, vincristine, doxorubicin, prednisone) in patients with follicular lymphoma (FL).

Material and methods Retrospective observational study including a cohort of FL patients treated with rituximab in combination with firstline CHOP chemotherapy, recruited from two university hospitals. The clinical response was assessed after the fourth cycle and when treatment was completed. Response criteria used were proposed by the International Working Group: complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), considered SD and PD for non-responders (NR). Gene polymorphisms were determined by fluorescent allelic discrimination. Statistical analysis was performed using statistical package SPSS 22.0.

Results 78 patients were included (64% men, average age 50.9 ± 13.1 years). Median number of rituximab cycles was 6.4 ± 1.2. The pharmacogenetic study was performed in 59 patients at the fourth cycle and in 76 (for rs767455) and 75 (for rs1800682) at the end of treatment. Distribution for response/genotypes were as follows: • after the fourth cycle: NR (TC=3 (100%)), PR (CC=3 (7.7%), TC=18 (46.2%), TT=18 (46.2%)), CR (CC=3 (17.6%), TC=9 (52.9%), TT=5 (29.4%)) (polymorphism rs767455); NR (CC=2 (66.7%), TC=1 (33.3%)), PR (CC=12 (30.8%), TC=17 (43.6%), TT=10 (25.6%)), CR (CC=3 (17.6%), TC=12 (70.6%), TT=2 (11.8%)) (polymorphism rs1800682); • when treatment was completed: NR (TC=3 (100%)), PR (CC=3 (16.7%), TC=6 (33.3%), TT=9 (50.0%)), CR (CC=4 (7.3%), TC=32 (58.2%), TT=19 (34.5%)) (polymorphism rs767455); NR (CC=2 (66.7%), TC=1 (33.3%)), PR (CC=4 (23.5%), TC=9 (52.9%), TT=4 (23.5%)), CR (CC=15 (27.3%), TC=26 (47.3%), TT=14 (25.5%)) (polymorphism rs1800682) No statistically significant differences were found between genotypes (rs767455; rs1800682) and clinical response to rituximab after the fourth cycle (p = 0.271; p = 0.204) or when treatment was completed (p = 0.171; p = 0.604).

Conclusion According to our results, gene polymorphisms rs767455 and rs1800682 do not appear to influence the response to treatment with rituximab associated with CHOP chemotherapy in FL.

References and/or Acknowledgements Hematology Department

No conflict of interest.

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