TY - JOUR
T1 - Nivolumab in the treatment of Hodgkin lymphoma
AU - Ansell, Stephen M.
N1 - Publisher Copyright:
© 2016 American Association for Cancer Research.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Despite an extensive immune infiltrate that is recruited to the tumor by malignant Reed-Sternberg cells in Hodgkin lymphoma, the antitumor immune response is ineffective and unable to eradicate the malignant cells. The ineffective immune response is in part due to PD-1 signaling that renders intratumoral immune cells anergic. Reed-Sternberg cells have been shown to upregulate expression of the PD-1 ligands, PD-L1 and PD-L2, due to either genetic alterations at chromosome 9p24.1 or Epstein-Barr virus infection, and these ligands suppress the function of PD-1+ intratumoral T cells. Blockade of PD-1 signaling has proven to be a highly successful therapeutic approach, and the use of the anti-PD-1 mAb nivolumab recently received accelerated approval by the FDAfor patients with classical Hodgkin lymphoma that has relapsed or progressed after autologous stem cell transplant and posttransplantation brentuximab vedotin. Initial clinical trials using nivolumab in this patient population resulted in high response rates that were durable. Adverse events associated with nivolumab included immune-mediated adverse reactions and infusion reactions, but these were well tolerated, allowing for continued nivolumab administration. Clinical trials are now in progress to test the use of nivolumab in combination with standard chemotherapy or with novel agents with a goal of improving the outcome of patients with Hodgkin lymphoma.
AB - Despite an extensive immune infiltrate that is recruited to the tumor by malignant Reed-Sternberg cells in Hodgkin lymphoma, the antitumor immune response is ineffective and unable to eradicate the malignant cells. The ineffective immune response is in part due to PD-1 signaling that renders intratumoral immune cells anergic. Reed-Sternberg cells have been shown to upregulate expression of the PD-1 ligands, PD-L1 and PD-L2, due to either genetic alterations at chromosome 9p24.1 or Epstein-Barr virus infection, and these ligands suppress the function of PD-1+ intratumoral T cells. Blockade of PD-1 signaling has proven to be a highly successful therapeutic approach, and the use of the anti-PD-1 mAb nivolumab recently received accelerated approval by the FDAfor patients with classical Hodgkin lymphoma that has relapsed or progressed after autologous stem cell transplant and posttransplantation brentuximab vedotin. Initial clinical trials using nivolumab in this patient population resulted in high response rates that were durable. Adverse events associated with nivolumab included immune-mediated adverse reactions and infusion reactions, but these were well tolerated, allowing for continued nivolumab administration. Clinical trials are now in progress to test the use of nivolumab in combination with standard chemotherapy or with novel agents with a goal of improving the outcome of patients with Hodgkin lymphoma.
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U2 - 10.1158/1078-0432.CCR-16-1387
DO - 10.1158/1078-0432.CCR-16-1387
M3 - Article
C2 - 27881581
AN - SCOPUS:85016944216
SN - 1078-0432
VL - 23
SP - 1623
EP - 1626
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 7
ER -