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Case Reports
. 2019 Jan 16;8(1):IJH10.
doi: 10.2217/ijh-2018-0009. eCollection 2019 Feb.

Checkpoint inhibition of PD-L1 and CTLA-4 in a child with refractory acute leukemia

Larisa Broglie  1   2   1   2 , Jill Gershan  1   1 , Michael J Burke  1   1
Affiliations
Case Reports

Checkpoint inhibition of PD-L1 and CTLA-4 in a child with refractory acute leukemia

Larisa Broglie et al. Int J Hematol Oncol. .

Abstract

Children with multiple relapsed or refractory leukemia have dismal survival. Research has identified engagement of immune checkpoint receptors (e.g., PD-1, PD-L1 and CTLA-4) as a mechanism for treatment resistance. For adult cancer, inhibitors of PD-1 (nivolumab) and CTLA-4 (ipilimumab) have shown promise with response rates ranging from 7 to 40%. In vitro studies using acute myeloid leukemia cell lines have shown that acute myeloid leukemia blasts may similarly utilize the PD-1/PD-L1 axis to evade an anticancer immune response. We report the first case of a pediatric patient with multiple relapsed/refractory leukemia treated with nivolumab, ipilimumab and 5-azacytidine who tolerated therapy with brief improvement of symptoms.

Keywords: acute leukemia; azacytidine; checkpoint inhibitor; epigenetic; ipilimumab; nivolumab; refractory; relapse.

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Conflict of interest statement

Financial & competing interests disclosure This publication was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Numbers UL1TR001436 and 1TL1TR001437 to L Broglie. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. Post-treatment serum cytokines.
Serum was obtained after 28 days of treatment with 5-azacytidine and nivolumab. Cytokine concentrations were analyzed by Eve Technologies (AB, Canada) using a Luminex-based platform. Control serum was obtained from normal adult donors. ****p < 0.0001; ***p < 0.001; **p < 0.01 and *p < 0.05.
<b>Figure 2.</b>
Figure 2.. Percent peripheral blasts.
The percent of peripheral blasts present during the 6 weeks of epigenetic and checkpoint inhibitor therapy are reported over time (days of therapy).
See this image and copyright information in PMC

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