Study of gene polymorphisms as predictors of treatment efficacy and toxicity in patients with indolent non-hodgkin lymphomas and mantle cell lymphoma receiving bendamustine and rituximab

Br J Haematol. 2019 Jan;184(2):223-231. doi: 10.1111/bjh.15582. Epub 2018 Sep 11.

Abstract

Bendamustine is used in combination with rituximab (BR) to treat indolent non-Hodgkin lymphomas (iNHL) and mantle cell lymphoma (MCL). The variability in treatment efficacy and toxicity could be related to single nucleotide polymorphisms (SNPs) in immune response genes. We would like to show a correlation between SNPs and treatment outcome in iNHL and MCL patients receiving BR. We investigated some SNPs that had already been associated with NHL outcome. Samples were genotyped for the IL2 (rs2069762), IL10 (rs1800890, rs10494879), VEGFA (rs3025039), IL8 (rs4073), CFH (rs1065489) and MTHFR (rs1801131) SNPs by allelic discrimination assays. We enrolled 70 patients that received rituximab 375 mg/m2 and bendamustine 90 mg/m2 every 28 days, both as first-line treatment and ≥ second-line regimens. Overall response rate was 97·1% (complete response [CR] rate 73·9%). Treatment toxicity included grade 3-4 neutropenia (24/70 patients), infections (21/70 patients; 1/70 grade 3), skin rash (26/70 patients; 2/70 grade 3). After a median follow-up of 24 months we did find any correlation between the analysed SNPs, CR rate and PFS. However, we demonstrated an association between the SNP in IL2 (rs2069762) and the onset of skin rash (P = 0·0001). Our study suggests a role for cytokine SNPs in bendamustine-related toxicity, which could represent a promising research field.

Keywords: Non-Hodgkin lymphoma; bendamustine; outcome; rituximab; single nucleotide polymorphisms.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Bendamustine Hydrochloride / administration & dosage
  • Bendamustine Hydrochloride / adverse effects
  • Drug Eruptions* / genetics
  • Drug Eruptions* / metabolism
  • Drug Eruptions* / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Interleukin-2* / genetics
  • Interleukin-2* / metabolism
  • Lymphoma, Mantle-Cell* / drug therapy
  • Lymphoma, Mantle-Cell* / genetics
  • Lymphoma, Mantle-Cell* / metabolism
  • Lymphoma, Mantle-Cell* / pathology
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Neutropenia / genetics
  • Neutropenia / metabolism
  • Neutropenia / pathology
  • Polymorphism, Single Nucleotide*
  • Rituximab / administration & dosage
  • Rituximab / adverse effects

Substances

  • IL2 protein, human
  • Interleukin-2
  • Rituximab
  • Bendamustine Hydrochloride