PDL1 Amplification Linked To Positive Response to Checkpoint Blockers

MedicalResearch.com Interview with

Aaron Goodman, MD Hematologist/Medical Oncologist Assistant Professor of Medicine UC San Diego Health

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: 

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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