Characterizing the Prognostic and Predictive Role of Immune Cell Population Changes Induced by Neoadjuvant PD-1 Inhibition in Clear Cell Renal Cell Carcinoma
Abstract
Objective and Rationale: Kidney cancer poses a significant and increasing burden on the American healthcare system. When the cancer appears to be confined to the kidney without spread to other organs, surgery to remove the tumor or the entire kidney is the current gold standard treatment. However, the cancer may return in approximately one-third of patients, and these patients may benefit from additional treatments, such as immunotherapy. However, we lack reliable means to identify these patients upfront and to predict their response to therapy. We are leading a multi-center clinical trial to assess the benefit of administering immunotherapy before surgery for kidney cancer to minimize the risk of the cancer returning. Using patient tissues from this trial, which recently completed accrual, we aim to understand the types of changes that occur within and surrounding tumors and in patients bloods after treatment with immunotherapy. With this information, we also aim to uncover whether there are features in the tumor or blood of patients with kidney cancer that would allow clinicians to predict response to immunotherapy. Applicability of the Research: Types of patients helped: Kidney cancer affects a broad spectrum of patients. Our trial has captured this diversity by enrolling representative adult patients of all ages, various ethnicities, and genders across the United States, including patients from Veterans Affairs hospitals. Thus, our study findings will be applicable to all groups of patients with kidney cancer in the American public. Specifically, we target patients with high-risk disease who might benefit from additional therapy aside from surgery. The study will help identify these patients upfront and predict their ability to respond to therapy. The study may also uncover ways in which response to therapy can be enhanced. Potential clinical applications, benefits, and risks: Clinically, using our study s findings, a simple upfront blood test in patients with newly diagnosed kidney cancer may suffice to predict whether a patient would benefit from early therapies, along with the specific type of therapy. The benefit of this would be a non-invasive test that provides precise information about the patient and his or her cancer to inform the optimal and most effective approach to treatment. This would allow clinicians to treat the cancer effectively without exposing patients to toxicities or delays from ineffective treatments. Since the study is specific to a particular type (the most common type) of kidney cancer, a foreseeable risk would be inaccuracies in gleaning this information for other, less common, forms of kidney cancer. In such cases, a biopsy to determine the type of cancer may be informative. Projected time for a clinically relevant outcome: The clinical trial has already completed accrual. We will be able to understand how tumors respond to immunotherapy by examining their tumors and bloods immediately at the time of surgery. This would allow us to generate a clinically relevant outcome as soon as 2023, with completion of our proposed analyses by 2025. By continuing to follow patients thereafter to see if the cancer returns, we would continue to gain important information each year for up to 5 years of follow-up on the trial. Contributions to advancing the field of kidney cancer research: Kidney cancer research is continually evolving with new combination treatments being developed. Our research will help provide an understanding of the tumor- and blood-related changes caused by immunotherapy, and, as a result, form the rationale for testing future drug-drug or even drug-radiation combinations that would enhance treatment effect. Together, our work will contribute to a growing field with the ultimate goal of effectively eliminating this disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210996
Entities
People
- Nirmish Singla
Organizations
- Johns Hopkins University
- United States Army