15 Jun PDL1 Amplification Linked To Positive Response to Checkpoint Blockers
MedicalResearch.com Interview with
Aaron Goodman, MD
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.
Goodman AM, Piccioni D, Kato S, et al. Prevalence of PDL1 Amplification and Preliminary Response to Immune Checkpoint Blockade in Solid Tumors. JAMA Oncol. Published online June 14, 2018. doi:10.1001/jamaoncol.2018.1701
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