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  • Publication of our analysis of 9p24.1/CD274(PD-L1)/ PDCD1LG2(PD-L2) alterations in a clinically annotated series of classical Hodgkin lymphomas (cHL) (J Clin Oncol. 2016;34(23):2690-7). Ninety-seven percent of all evaluated cHLs had concordant alterations of the PD-L1 and PD-L2 loci, including copy gain in 56% of patients and amplification in 36% of patients. Progression-free survival was significantly shorter for patients with 9p24.1 amplification who were also more likely to have advanced stage disease. In cHL, the near-uniform alterations of the PD-L1/PD-L2 loci likely explain the activity of PD-1 blockade in this disease.
  • FDA approval for PD-1 blockade (nivolumab therapy) in relapsed/ refractory cHL in May, 2016. The approval was based on data from the pilot study (N Engl J Med 372:311-319, 2015) and subsequent registration trial (Lancet Oncology 2016 July 20. Epub ahead of print), including a response rate of 66-87% in heavily pre-treated patients.
  • Publication of our comprehensive genomic analysis of primary central nervous system lymphoma (PCNSL) and primary testicular lymphoma (PTL) (Blood. 2016;127(7):869-81). To identify targetable genetic features of PCNSL and PTL, we characterized their recurrent somatic mutations, chromosomal rearrangements, copy number alterations (CNAs) and associated driver genes and compared these comprehensive genetic signatures to those of diffuse LBCL and primary mediastinal large B-cell lymphoma (PMBL). PCNSLs and PTLs exhibit near-uniform, often biallelic, CDKN2A loss with rare TP53 PCNSLs and PTLs also utilize multiple genetic mechanisms to target key genes and pathways and exhibit near-uniform oncogenic Toll-like receptor signaling due to MYD88 mutation and/or NFKBIZ amplification, frequent concurrent B-cell receptor pathway activation and deregulation of BCL6. Of great interest, PCNSLs and PTLs also have frequent 9p24.1/PD-L1/PD-L2 CNAs and additional translocations of these loci, structural bases of immune evasion that are shared with PMBL. A clinical trial of PD-1 blockade (nivolumab therapy) in relapsed/refractory PCNSL and PTL is scheduled to open in early fall, 2016.

 

 

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