Explore the Severe Immunotherapy Complications Service

Overview

We are in the midst of an exciting revolution in the treatment of cancer. By harnessing and enhancing the body’s immune system using novel therapies such as immune checkpoint inhibitors, we can reduce the amount of tumor burden in patients and, in a subset of patients and cancers, achieve long-lasting remission. However, these therapies are often limited by the unchecked activation of the immune system which can result in immune-related adverse events (irAEs). This toxicity can affect nearly every organ system, ranging from a minor rash to severe dermatological, gastrointestinal, pulmonary, or cardiac complications.

As more patients are treated with immunotherapy, there is a corresponding increase in the number of patients experiencing toxicity which highlights the urgent need to understand how and why immuno-toxicities occur and develop rigorous pathways for how to best manage them.

A First-of-its Kind Program

The Severe Immunotherapy Complications (SIC) Service and Clinical-Translational Research Effort, the first-of-its kind across the country, has been at the forefront of developing expertise in the recognition of complex irAE presentations and the management of toxicity. Since October 2017, this multidisciplinary group of clinicians and researchers have been involved in the care of every patient admitted with a suspected irAE after checkpoint blockade immunotherapy.

Each patient presenting to the Mass General Cancer Center with clinical signs or symptoms consistent with an irAE is seen by one of the Cancer Center’s 12 SIC service oncologists, all of whom have expertise in managing severe irAEs. The SIC team can be paged to see admissions 7 days a week, 24 hours a day. The oncologists round daily, review all data related to irAEs, examine and evaluate all patients being treated for irAEs and discuss patient care with the relevant SIC service subspecialists. There are SIC subspecialists from the oncology, allergy/immunology, cardiology, dermatology, endocrinology, hematology, nephrology, neurology, ophthalmology, pulmonology, gastroenterology, infectious disease, and rheumatology divisions.

Kerry Reynolds, MD
Kerry Reynolds, MD, Director, Severe Immunotherapy Complications Program

Led by Kerry Reynolds, MD and Chloe-Alexandra Villani, PhD, this multidisciplinary team now comprises more than 50 individuals across 19 areas of the hospital and includes 6 postdoctoral clinical fellows that bridge between clinical and translational efforts, working in both the clinic and the laboratory of Dr. Villani.

Members of the SIC team also advise and educate the larger network community via case discussions and literature review in an educational lecture series every other week. The experts serve as the central referral source for complex cases of irAEs in the city, the state, and beyond. The guiding principle of the clinical SIC service is to develop expertise in recognition and management of irAEs and to extend that expertise to the larger network community and subspecialty arenas.

Our work to date shows that a highly subspecialized care team focused on irAEs can improve clinical outcomes for patients while also creating infrastructure needed to drive future research on irAEs. Importantly, the process of developing expertise in clinical care interfaces directly with development of well-defined clinical phenotypes that can be used to understand the spectrum of these events.

The Mass General Difference

What makes our approach so novel is that we have crossed traditional departmental boundaries at our institution and brought together expertise from each and every relevant clinical division, along with cutting edge scientists, to form a new hybrid community with a common goal. This was possible given that Massachusetts General Hospital is a “general” hospital with previous expertise in autoimmunity across disease states and, importantly, because there exists an undeterrable sense of community and dedication to our patients.

Understanding the Mechanisms Driving irAEs

The SIC service has also joined together to set up an infrastructure for specimen collection, under the leadership of Dr. Alexandra-Chloe Villani, with the hope of understanding the mechanisms driving irAEs. One of our goals is to develop better therapies for treating autoimmune toxicities, while maintaining anti-tumor immunity.

Villani lab
Villani Lab

This group of scientists and clinicians are working towards developing a better understanding of the biological players and underlying molecular and cellular mechanisms involved in driving irAEs by directly studying patient blood and matched affected tissue samples using a range of systems immunology, immunogenomics and single-cell ‘omics’ strategies.

Visit the Villani lab

 


Videos


Publications

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Team Interviews

In this new interview series, Kerry Reynolds, MD, director of the SIC program, sits down with a SIC team member for a deeper-dive into their work.

 

Facing Immunotherapy: A Guide for Patients and Their Families

Facing Immunotherapy book cover imageAuthored by Mass General physicians, Facing Immunotherapy is for anyone whose life is affected by cancer and who is considering (or is receiving) immunotherapy. This book provides easily readable and trustworthy information, which is divided amongst twenty-six chapters that ask and answer pertinent questions about immunotherapy and its medical, surgical, and psychiatric/psychological components. Learn more.