Year of Grant: 2016

Location: United States

Certain large B-cell lymphoma (LBCL) subtypes, including primary central nervous system lymphoma (PCNSL) and primary testicular lymphoma (PTL), present as localized masses in specific extranodal organs. PCNSLs and PTLs
have inferior responses to current empiric treatment regimens and are considered incurable with standard therapies. Nearly 50% of patients with PCNSL relapse within 2 years of diagnosis and one third of patients have primary refractory disease.

The study group has characterized the genetic features of PCNSL and PTL to identify more rational targets for genetic therapy. PCNSLs and PTLs utilize multiple genetic mechanisms to target key genes and pathways and exhibit near-uniform alterations of the Toll-like receptor and B cell receptor signaling
pathways. In a small pilot series previously, patients with recurrent PCNSL exhibited near uniform sensitivity to PD-1 blockade.

This proposed single arm phase II clinical trial seeks to enrol 45 PCNL patients and 20 PTL patients over a 3-year period with the aim to:

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1. Define the PD-L1/PD-L2 genetic alterations and associated protein expression in patients with newly diagnosed and recurrent PCNSL and PTL;

2. Assess the activity of PD-1 blockade, alone and in combination with additional targeted agents in phase 2 clinical trial for patients with recurrent PCNSL and PTL; and

3. Elucidate mechanisms of response and resistance to PD-1 blockade and the combination regimen in these patients.

NOTE: This study was an application for the 2016 RTFCCR/LLS International Research Grant to advance immunotherapy research for blood cancer.