2023 ASCO Annual Meeting- “New Strategies for Personalized Immunotherapy”

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June 3, 2023

Irby Hunter, Jr., MD Medical Director Oncology Independent Medical Education Inc & Executive Publisher Oncology Disparities Peer Reviewed Scientific Journal

On June 4, the 2023 ASCO Annual Meeting Education Session “Rational Combinations: The Road to Personalized Immunotherapy” will explore new strategies for personalizing immunotherapy ⁽¹⁾. Immunotherapy is an innovative breakthrough treatment for certain cancer types ⁽¹⁾. Unlike traditional chemotherapy and radiation therapy, immunotherapies do not target the cancer itself ⁽²⁾. The science of immunotherapy relies on the harnessing or reinvigorating the immune system so that it recognizes and attacks cancer cells ⁽²⁾. However, the efficacy of immunotherapy in the general population across common cancer types is limited and variable ⁽¹⁾. Many patients suffer from cancer types that are initially resistant to immunotherapy, and in other cases immunotherapy loses its effectiveness ⁽¹⁾. This well-known clinical hardship calls for an urgent need for active therapies.

Speakers for the forementioned Education Session, will explore mechanism of resistance to immunotherapy, and review recent clinical trials of new immunotherapy strategies ⁽¹⁾. Community oncologists will be provided with next steps for immunotherapy in terms of new trials and ideas to address resistance ⁽¹⁾. Likewise, community oncologists will learn that multiple factors can contribute to the development of resistance to immunotherapy ⁽¹⁾. Immunotherapy based on immune checkpoints inhibitors (ICIs) is a common clinical approach for treatment of patients with poor prognosis when other first-line therapies have failed. Approximately 70% of patients being treated with immunotherapy are classified as non-responders. Multiple factors are related to immunotherapy resistance to include: characteristics of the tumor microenvironment (TME); presence of tumor infiltrating lymphocytes (TILS), such as CD8 + T cells associated treatment-response; presence of tumor associated macrophages (TAMs); activation of certain regulators (like PIK3y or PAX4) found present in non-responders; a low percentage of PD-L1 expressing cells; tumor mutational burden (TMB); gain or loss of antigen-presenting molecules; genetic and epigenetic alterations correlated with resistance ⁽⁴⁾. Education session speaker Harriet M. Kluger, MD, of Yale University, plans to share that “the more we learn about why some people respond and why others don’t, the more likely we will be to develop new drugs that can be added to what we already have, or replace what we already have, so that we can increase the percentages of patients who are cured from certain cancers” ⁽¹⁾. Dr. Kluger will also highlight recent research efforts to evaluate strategies to influence the microenvironment as a means to overcome resistance ⁽¹⁾.

Additionally, during the session, Eylan Ruppin, MD, PhD, of the National Cancer Institute, will discuss research efforts to characterize the transcriptome of the tumor immune microenvironment and the use this molecular information to stratify patients for immunotherapy ⁽¹⁾. Since 2018, Dr. Ruppin and colleagues have developed and published several algorithms that use tumor transcriptomics as predictive biomarkers for immunotherapy ⁽¹⁾. These include IMPRES (immune-predictive score) algorithm, which predicts responses to checkpoint inhibition in melanoma, and the SELECT (synthetic lethality and rescue mediated precision oncology via the transcriptome) algorithm, which predicts responses to targeted and immunotherapy in multiple tumor types ^(4,5). Dr. Ruppin will also share data about using liquid biopsy to characterize circulating T cells at the single-cell level to learn about the state of immune cells in the tumor microenvironment ⁽¹⁾.

Session chair, Siwen Hu-Lieskovan, MD, PhD, of the Huntsman Cancer Institute, will summarize key clinical trials of immunotherapy combinations. Dr. Hu-Lieskovan will discuss the design of the ComboMATCH trial that will test combinations of drugs depending on mutational profiles, as there may be a higher likelihood of hitting the driver mutation(s) ⁽⁵⁾. She will discuss the design of the ImmunoMatch trial and how the trial is geared towards the evaluation of how relevant biomarkers such tumor molecular burden and gene expression profile could help separate patients into biological groups with distinct mechanisms of resistance and facilitate successful development of combination immunotherapy ⁽⁶⁾. Finally, Dr Hu-Lieskovan’s comprehensive message to the audience will be to state that the goal of these studies and others is to be able to use biomarkers to identify patients who are most likely to benefit from a specific combination as well as to use the study results to personalize the immunotherapeutic approach to cancer treatment. ⁽¹⁾

Stayed tuned for full report on this Education Session and how personalizing immunotherapy my serve as a vital tool to overcome health disparities.

References:

1. ASCO Daily News. 2023. New Strategies for Personalizing Immunotherapy. Saturday June 3, 2023. 2023 ASCO Annual Meeting.
2. Boldt, Clayton. 2020. Which Cancers can be treated with immunotherapy? November 6. 2020. The University of Texas MD Anderson Cancer Center. Retrieved from https://www.mdanderson.org/cancerwise/what-cancers-can-be-treated-with-immunotherapy.h00-159386679.html on June 3, 2023.

3. Perez-Ruiz, Elisabeth, Melero, Ignacio, Kopecka, Joanna, Sarmento, Ribeiro, Garcia-Aranda, Marlina, De Las Rivas, Javier. 2020. Cancer immunotherapy resistance based on immune checkpoints: Targets, biomarkers, and remedies. July 15, 2020. Drug Resistance Update. Retrieved from Cancer immunotherapy resistance based on immune checkpoints inhibitors: Targets, biomarkers, and remedies – PubMed (nih.gov) on June 3, 2023. doi: 10.1016/j.drup.2020.100718

4. Auslander N, Zhang G, Lee JS, et al. Robust prediction of response to immune checkpoint blockade therapy in metastatic melanoma. Nat Med:24 (10): 1545-1549

5. Lee, JS, Nair NU, Dinstang G. et al. Synthetic lethality-mediated precision oncology via the tumor transcriptome. Cell. 2021;184(9): 2487-25012.e13.

6. National Cancer Institute. NCI-MATCH Trial (Molecular Analysis for Therapy Choice). www.cancer/gov/about-cancer/treatment/clinical-trials/nci-supported/nci-match. Accessed April 3, 2023.