The optimal means of quantifying PD-L1 and understanding unexplained responses are being explored. Because of space limitations, the reader is referred to a good review of recent results using antibodies and of current challenges in establishing reliable techniques to identify which tumors will respond and why some will not.2

The exciting results with nivolumab include a study published in The New England Journal of Medicine, which included 23 patients with resistant Hodgkin’s lymphoma, most with the nodular sclerosis type and after failure of autotransplant.

It found responses in 20 patients (87%), four of which were complete, with 86% progression-free survival at 6 months.It may or may not be noteworthy that three of the four patients with complete responses had not received brentuximab.

Is there something specific about Hodgkin’s lymphoma or can any hematologic malignancy be effectively treated? PD-L1 is overexpressed on Reed-Sternberg cells and, particular to the nodular sclerosis type, chromosome 9p24.1 amplification is associated with increase in PD-1 ligands. Viruses can also use the PD-1 axis to avoid immune attack.

In EBV-related Hodgkin’s lymphoma, post-transplant lymphoma, and nasopharyngeal cancer, PD-1 blockade has been used successfully, but not in Burkitt lymphoma or HHV-8 Kaposi sarcoma, possibly explained by differences in protein signaling. There are clinical trials ongoing in most hematologic malignancies.

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Results in non-Hodgkin’s lymphoma presented at the 2014 American Society of Hematology annual meeting by the same Hodgkin’s lymphoma investigators showed 15% to 40% responses in small patient numbers, and studies are continuing in diffuse large B-cell and follicular lymphomas.

Cancer just can’t be smarter than we are. Although it has taken a long time to discover, cancer’s been using the same tricks in its various manifestations, which we couldn’t identify while we separated them by histology. As we continue to gain knowledge, the future for cancer research looks brighter and a lot more fascinating.

References

  1. Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372(4):311-319.
  2. Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015;14(4):847-856.