Cell Death Biomarker May Help Predict Melanoma PD-1 Responders

Dr. Roxana S. Dronca, M.D Assistant Professor of Oncology Assistant Program Director of Hematology-Oncology Fellowship Mayo Clinic College of Medicine Rochester, Minnesota MedicalResearch.com Interview with:
Dr. Roxana SDronca, M.D
Assistant Professor of Oncology
Assistant Program Director of Hematology-Oncology Fellowship
Mayo Clinic College of Medicine
Rochester, Minnesota 

Medical Research: What is the background for this study? What are the main findings?

Dr. Dronca: We previously showed that Bim (BCL-2-interacting mediator of cell death ) is a downstream signaling molecule of PD-1 pathway reflecting the degree of PD-1 interaction with its ligand PD-L1 (unpublished data).

In the current study we found that patients who experienced clinical benefit (CR/PR/SD) after 4 cycles of anti-PD1 therapy had higher frequency of Bim+ PD-1+ T-killer cells in the peripheral blood at baseline compared to patients with radiographic progression, likely reflecting an abundant PD-1 interaction with its tumor-associated ligand PD-L1 (B7-H1). In addition, the frequencies of Bim+ PD-1+ CD8 T cells decreased significantly after the first 3 months of treatment in responders compared to nonresponders, indicating tumor regression and therefore less PD-1 engagement with tumor-associated PD-L1.

Medical Research: What should clinicians and patients take away from your report?

Dr. Dronca: Our findings could help physicians select patients with melanoma (and possibly other malignancies) who are most likely to benefit from PD-1 blockade, follow patients during treatment identify those who have late responses or are acquiring resistance to these agents during the course of treatment, thereby exposing fewer patients to inadequate treatments and their associated toxicities and costs. A great advantage of our approach lies in the ease of serial peripheral blood testing as compared to repeated invasive tissue biopsies.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Dronca: We are planning to validate these results on a larger prospective cohort on patients with melanoma and also lung cancer. We are also testing this marker in patients with other cancers such as chronic lymphocytic leukemia.

Citation: Abstract presented at:

CRI-CIMT-EATI-AACR – The Inaugural International Cancer Immunotherapy Conference:
Translating Science into Survival

September 16 – 19, 2015 • Sheraton New York Times Square Hotel • New York, NY

A007 Bim as a predictive T cell biomarker for response to anti-PD-1 therapy in metastatic melanoma (MM). Roxana S Dronca, Svetomir N Markovic, Lisa A Kottschade, Wendy Nevala, Haidong Dong.

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Dr. Roxana S. Dronca, M.D (2015). Cell Death Biomarker May Help Predict Melanoma PD-1 Responders