15 Jun PDL1 Amplification Linked To Positive Response to Checkpoint Blockers
MedicalResearch.com Interview with
Dr. Goodman
Aaron Goodman, MD
Hematologist/Medical Oncologist
Assistant Professor of Medicine
UC San Diego Health
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Response rates to PD-1/PD-L1 blockade in solid tumors are reported at 10-20%. Remarkably, response rates of 65% to 87% have been reported in patients with refractory classical Hodgkin lymphoma treated with checkpoint inhibitors.
In nodular sclerosing Hodgkin lymphoma, amplification of the chromosomal region 9p24.1, which contains the genes PD-L1 (CD274), PDCD1LG2 (PD-L2)and JAK2, is directly correlated with increased expression of these proteins on Reed–Sternberg cells.
Overall, 105 of 108 (97%) biopsies from patients with newly diagnosed classical Hodgkin lymphoma have increased PD-L1 and PDCD1LG2 copy numbers. The prevalence and utility of PD-L1amplification as a response biomarker to PD-1/PD-L1 blockade is unknown in other tumors.
We sought to determine the prevalence and utility of PD-L1 amplification as a response biomarker to PD-1/PD-L1 blockade in solid tumors.
MedicalResearch.com: What should readers take away from your report?
Response: In this study that included 118,187 tumor samples from a de-identified database as well as a subset of 2,039 samples from a clinically annotated database, the prevalence of PD-L1 amplification was 0.7%. The objective response rate for patients with solid tumors harboring PD-L1 amplification was 67% with a median PFS of 15.2 months. PD-L1 amplification occurs in a small subset of malignancies, however, PD-L1 amplification appears to be an excellent biomarker for response to PD-1 blockade (independent of tumor mutational burden.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Further large-scale prospective studies of PD-L1-amplified cancers are warranted in order to confirm the responses to checkpoint blockade described herein, even in the absence MSI, high PD-L1 expression, and a high TMB.
Disclosures: Speaking fees from Seattle Genetics.
Citations:
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Last Updated on June 15, 2018 by Marie Benz MD FAAD