Predictive Value of Cytokines and Immune Activation Biomarkers in AIDS-Related Non-Hodgkin Lymphoma Treated with Rituximab plus Infusional EPOCH (AMC-034 trial)

Clin Cancer Res. 2016 Jan 15;22(2):328-36. doi: 10.1158/1078-0432.CCR-14-0466. Epub 2015 Sep 17.

Abstract

Purpose: The aims of this study were to determine whether pretreatment plasma levels of cytokines and immune activation-associated molecules changed following treatment for AIDS-NHL with rituximab plus infusional EPOCH, and to determine whether pretreatment levels of these molecules were associated with response to treatment and/or survival.

Experimental design: We quantified plasma levels of B-cell activation-associated molecules (sCD27, sCD30, and sCD23) and cytokines (IL6, IL10, and CXCL13) before and after the initiation of treatment in persons with AIDS-NHL (n = 69) in the AIDS Malignancies Consortium (AMC) 034 study, which evaluated treatment of AIDS-NHL with EPOCH chemotherapy and rituximab.

Results: Treatment resulted in decreased plasma levels of some of these molecules (CXCL13, sCD27, and sCD30), with decreased levels persisting for one year following the completion of treatment. Lower levels of CXCL13 before treatment were associated with complete responses following lymphoma therapy. Elevated levels of IL6 pretreatment were associated with decreased overall survival, whereas higher IL10 levels were associated with shorter progression-free survival (PFS), in multivariate analyses. Furthermore, patients with CXCL13 or IL6 levels higher than the median levels for the NHL group, as well as those who had detectable IL10, had lower overall survival and PFS, in Kaplan-Meier analyses.

Conclusions: These results indicate that CXCL13, IL6, and IL10 have significant potential as prognostic biomarkers for AIDS-NHL.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / blood
  • Acquired Immunodeficiency Syndrome / immunology
  • Adult
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / immunology*
  • Cyclophosphamide / therapeutic use
  • Cytokines / blood*
  • Disease-Free Survival
  • Doxorubicin / therapeutic use
  • Etoposide / therapeutic use
  • Humans
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Activation / immunology
  • Lymphoma, AIDS-Related / blood
  • Lymphoma, AIDS-Related / drug therapy
  • Lymphoma, AIDS-Related / immunology
  • Lymphoma, Non-Hodgkin / blood
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / immunology
  • Prednisone / therapeutic use
  • Rituximab / therapeutic use*
  • Vincristine / therapeutic use

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Cytokines
  • Rituximab
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • EPOCH protocol