Overcoming the immune-related adverse events that limit the use of immune checkpoint therapies in some cases requires a better understanding of the biology of these events.
One of the last in-person events convened by either the Society for Immunotherapy of Cancer (SITC) or the American Association for Cancer Research (AACR) before the COVID-19 pandemic put travel and large-scale gatherings on hold was a joint workshop titled, “The Cancer Biology Underlying Immunotherapy-Induced Autoimmunity.” A review of the workshop is published in the official journal of SITC, the Journal of Immunotherapy of Cancer (JITC; doi: 10.1136/jitc-2021-002627); a summary of the next SITC–AACR joint workshop will appear in the AACR journal Cancer Immunology Research (CIR). Here, the co-organizers of the March 2020 workshop—Lisa H. Butterfield of the Parker Institute for Cancer Immunotherapy, San Francisco, CA, and the University of California San Francisco, San Francisco, CA; Elizabeth M. Jaffee of the Sidney Kimmel Comprehensive Cancer Center at The Johns Hopkins University School of Medicine, Baltimore, MD; and Arlene H. Sharpe of Harvard Medical School, Boston, MA—shared their thoughts on the success of the workshop and how it will accelerate the pace of progress against immune-related adverse events (irAE) in the future with CIR's Senior Associate Editor, Karen Honey.
What precipitated the workshop from both a biological and a clinical perspective?
Jaffee: Immune checkpoint therapies have become the fourth pillar of cancer therapy. They have turned several deadly cancers into long-term chronic diseases. These therapies have a unique toxicity profile: They can cause significant immune-mediated toxicities and the severest forms can result in multi-organ toxicities and, in some cases, death. For patients at significant risk of death from their cancers, the risk/benefit ratio is worth it. However, we need to learn more about the pathogenesis of these toxicities, who is at risk for these toxicities, and how to intercept the toxicities early if we are to develop new treatment and prevention strategies and improve outcomes for patients as well as expand the use of immune checkpoint therapies to additional cancer indications and to treat patients with early-stage cancer. To better understand the biology behind immune-mediated toxicities, several leaders asked SITC and AACR to support a multidisciplinary workshop, bringing together experts from different fields including cancer, immunology, autoimmunity, neurology, cardiology, hepatology, and pulmonary to share information and identify further areas of research to address the issue.
Collaboration is key to driving progress—what have the two organizations brought to the table to help further this project?
Butterfield: AACR and SITC harnessed their respective expertise to develop a multidisciplinary workshop that was a perfect fit for both professional societies. AACR brought their interest and expertise in clinical cancer biology and patient toxicities; SITC brought their focus on cancer immunotherapy and checkpoint blockade mechanisms. Together, we created a program that tied these areas together to provide a forum in which we could gain new insights into the clinical toxicity issues of checkpoint blockade and the biology of the organ site–specific autoimmunity effects.
What do you think were the biggest accomplishments of the workshop?
Sharpe: This meeting had several important outcomes that are leading to next steps to address the issue of immunotherapy-induced autoimmunity and inflammation. First, the group identified datasets linking polymorphisms with risk of specific autoimmune diseases. Some of these polymorphisms are associated with response to immune checkpoint therapies and can be further assessed for predicting immune-related toxicities. Second, the group identified the need for new animal models that would facilitate uncovering mechanisms that cause the immune-mediated events. Third, the group recommended supporting a national biobank linked to immune checkpoint therapy outcomes data that can be used to identify biomarkers that would predict who is at risk for different toxicities. In addition, it was important that participants included leaders from academia, government, industry, and foundations and investigators with a broad range of expertise because this has stimulated new connections and will hopefully catalyze future collaborations.
How do you think that the published review of the workshop can promote advances in addressing irAEs?
Butterfield: We hope that this review will be a call to action that encourages key stakeholders to lead progress in the core areas identified as important during the workshop. Unfortunately, the workshop was held just before COVID-19 was declared a pandemic. As with many other activities, the next steps following this meeting have been on hold. Our hope is that the article and this companion piece will reignite interest in moving these action items forward. In particular, by drawing renewed attention to the topic and providing a citable work that we can use in discussions with funders and other organizations, we hope to catalyze new collaborations and funding opportunities for irAE research.
What challenges can you foresee to robust progress being made rapidly in the field of irAE research?
Sharpe: Overall, irAEs are an uncommon clinical problem, and the low frequency of irAEs of a given subtype makes it challenging for individual institutions to acquire sample sets large enough for deep correlative studies. Collaboration across multi-institutional and multispecialty studies is essential to increase sample size for mechanistic studies of specific irAEs. It is critical that we form a national group to coordinate these efforts and facilitate collaborations to advance irAE research.
What can AACR and SITC do to accelerate the pace of progress in irAE research?
Jaffee: Both AACR and SITC have the expertise to convene additional follow-up meetings and the ability to identify additional experts willing to work on this problem, including in society-sponsored working groups. In addition, both may be able to encourage financial support from multiple sectors. In this way, we will make strides toward solving the challenges of irAEs.