While clinical data are limited for PD-1 inhibition in patients with T-NHL, “disastrous results” have not been reported thus far, Dr Ludin and Dr Zon added.

Nevertheless, careful research is needed to ensure that immunotherapies activating T cells do not inadvertently fuel progression of T cell malignancies.


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But the German and Swiss team noted that their findings could also open the door to new avenues of investigational treatment.

“These patients could be helped by medications that reverse the loss of PD-1 signaling and thereby destroy the [T-NHL] cells,” suggested senior study author Jürgen Ruland, MD, of the Technische Universität München in Germany.6 “This type of medication already exists for other forms of cancer…use with T cell non-Hodgkin lymphoma should also be considered.”

In patients where there is a risk of malignant T cell proliferation, other treatment strategies should be considered.

In cell-line and mouse model experiments, the researchers found preliminary evidence that PI3K inhibition with idelalisib induced the death of some lymphoma cells and significantly prolonged mouse survival times.

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This route may, some suspect, be a safer strategy than PD-1 inhibition among some patients. Further study is needed, however, to determine which patients are at risk of this “dark side” of immune checkpoint inhibition.

References

  1. Hahn AW, Gill DM, Agarwal N, Maughan BL. PD-1 checkpoint inhibition: toxicities and management. Urol Oncol. 2017;35:701-7. doi: 10.1016/j.urolonc.2017.08.005
  2. Wartewig T, Kurgyis Z, Keppler S, et al. PD-1 is a haploinsufficient suppressor of T cell lymphomagenesis. Nature. 2017;552:121-5. doi: 10.1038/nature2464
  3. Ludin A, Zon LI. Cancer immunotherapy: The dark side of PD-1 receptor inhibition. Nature. 2017;552(7683):41-2. doi: 10.1038/nature24759
  4. Han P, Gopalakrishanan C, Yu H, Wang E. Gene regulatory network rewiring in the immune cells associated with cancer. Genes. 2017;7:308. doi: 10.3390/genes8110308
  5. Lesokhin AM, Ansell SM, Armand P, et al. Nivolumab in patients with relapsed or refractory hematologic malignancy: preliminary results of a phase Ib study. J Clin Oncol. 2016;34:2698-704. doi: 10.1200/JCO.2015.65.9789
  6. Lymphoma: important tumor suppressor discovered in immune cells [news release]. Munich, Germany: Technical University of Munich; May 12, 2017. https://www.cancertherapyadvisor.com/home/cancer-topics/general-oncology/. Accessed December 2017.