Efforts are underway at Mass General Cancer Center to blunt immune complications that come with lifesaving treatment. Read more from Science.
Severe Immunotherapy Complications Service
Severe Immunotherapy Complications Service and Clinical-Translational Research Effort
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Your gift to the Severe Immunotherapy Complications Service and Clinical-Translational Research Effort at Mass General will help our team address the urgent need to understand how and why immune-related adverse events occur. With your support, we will achieve our common goal of understanding and treating these side effects so patients can continue on their lifesaving immunotherapy treatments.
Explore the Severe Immunotherapy Complications Service
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.
Researchers take aim at cancer drugs’ toxic side effects
Learn more about Mass General's Severe Immunotherapy Complications program in Science.
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.
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.
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.
Meet the Team
Meet the Severe Immunotherapy Complications Service and Clinical-Translational Research's multidisciplinary team of clinicians and researchers.
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- Dougan M, Pietropaolo M. Time to dissect the autoimmune etiology of cancer antibody immunotherapy. J Clin Invest. 2020;130(1):51-61. doi:10.1172/JCI131194
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- Rogiers A, Pires da Silva I, Tentori C, et al. Clinical impact of COVID-19 on patients with cancer treated with immune checkpoint inhibition. J Immunother Cancer. 2021;9(1):e001931. doi:10.1136/jitc-2020-001931
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- Dougan M, Wang Y, Rubio-Tapia A, Lim JK. AGA Clinical Practice Update on Diagnosis and Management of Immune Checkpoint Inhibitor Colitis and Hepatitis: Expert Review. Gastroenterology. 2021;160(4):1384-1393. doi:10.1053/j.gastro.2020.08.063
- Molina GE, Yanovsky RL, Wei EX, Chen ST. Missed drug-induced bullous pemphigoid leads to longer immunosuppression than recognized cases: A 9-year retrospective review. J Am Acad Dermatol. 2020;82(5):1255-1258. doi:10.1016/j.jaad.2019.12.059
- Drobni ZD, Alvi RM, Taron J, et al. Association Between Immune Checkpoint Inhibitors With Cardiovascular Events and Atherosclerotic Plaque. Circulation. 2020;142(24):2299-2311. doi:10.1161/CIRCULATIONAHA.120.049981
- Chu JN, Choi J, Ostvar S, et al. Cost-effectiveness of immune checkpoint inhibitors for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer. Cancer. 01 2019;125(2):278-289. doi:10.1002/cncr.31795
- Cole S, Zibelman M, Bertino E, Yucebay F, Reynolds K. Managing Immuno-Oncology Toxicity: Top 10 Innovative Institutional Solutions. Am Soc Clin Oncol Educ Book. Jan 2019;39:96-104. doi:10.1200/EDBK_100018
- Lin JJ, Chin E, Yeap BY, et al. Increased Hepatotoxicity Associated with Sequential Immune Checkpoint Inhibitor and Crizotinib Therapy in Patients with Non-Small Cell Lung Cancer. J Thorac Oncol. Jan 2019;14(1):135-140. doi:10.1016/j.jtho.2018.09.001
- Sade-Feldman M, Yizhak K, Bjorgaard SL, et al. Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma. Cell. Jan 2019;176(1-2):404. doi:10.1016/j.cell.2018.12.034
- Larimer BM, Bloch E, Nesti S, et al. The Effectiveness of Checkpoint Inhibitor Combinations and Administration Timing Can Be Measured by Granzyme B PET Imaging. Clin Cancer Res. Feb 2019;25(4):1196-1205. doi:10.1158/1078-0432.CCR-18-2407
- Awadalla M, Golden DLA, Mahmood SS, et al. Influenza vaccination and myocarditis among patients receiving immune checkpoint inhibitors. J Immunother Cancer. Feb 2019;7(1):53. doi:10.1186/s40425-019-0535-y
- Bello E, Cohen JV, Mino-Kenudson M, Dougan M. Antitumor response to microscopic melanoma in the gastric mucosa mimicking ipilimumab-induced gastritis. J Immunother Cancer. Feb 2019;7(1):41. doi:10.1186/s40425-019-0524-1
- Criss SD, Mooradian MJ, Sheehan DF, et al. Cost-effectiveness and Budgetary Consequence Analysis of Durvalumab Consolidation Therapy vs No Consolidation Therapy After Chemoradiotherapy in Stage III Non-Small Cell Lung Cancer in the Context of the US Health Care System. JAMA Oncol. Mar 2019;5(3):358-365. doi:10.1001/jamaoncol.2018.5449
- Reynolds KL, Guidon AC. Diagnosis and Management of Immune Checkpoint Inhibitor Associated Neurologic Toxicity: Illustrative Case and Review of the Literature. Oncologist. Apr 2019;24(4):435-443
- Leaf RK, Ferreri C, Rangachari D, et al. Clinical and laboratory features of autoimmune hemolytic anemia associated with immune checkpoint inhibitors. Am J Hematol. May 2019;94(5):563-574. doi:10.1002/ajh.25448
- Faje A, Reynolds K, Zubiri L, et al. Hypophysitis secondary to nivolumab and pembrolizumab is a clinical entity distinct from ipilimumab-associated hypophysitis. Eur J Endocrinol. Jun 2019;doi:10.1530/EJE-19-0238
- Mooradian MJ, Nasrallah M, Gainor JF, et al. Musculoskeletal rheumatic complications of immune checkpoint inhibitor therapy: A single center experience. Semin Arthritis Rheum. Jun 2019;48(6):1127-1132. doi:10.1016/j.semarthrit.2018.10.012
- Sise ME, Seethapathy H, Reynolds KL. Diagnosis and Management of Immune Checkpoint Inhibitor-Associated Renal Toxicity: Illustrative Case and Review. Oncologist. Jun 2019;24(6):735-742. doi:10.1634/theoncologist.2018-0764
- Zhang L, Jones-O'Connor M, Awadalla M, et al. Cardiotoxicity of Immune Checkpoint Inhibitors. Curr Treat Options Cardiovasc Med. Jun 2019;21(7):32. doi:10.1007/s11936-019-0731-6
- Molina GE, Allen IM, Hughes MS, et al. Prognostic Implications of Co-Occurring Dermatologic and Gastrointestinal Toxicity from Immune Checkpoint Inhibition Therapy for Advanced Malignancies: A Retrospective Cohort Study. J Am Acad Dermatol. Jul 2019;doi:10.1016/j.jaad.2019.07.049
- Zhang ML, Neyaz A, Patil D, Chen J, Dougan M, Deshpande V. Immune-Related Adverse Events in the Gastrointestinal Tract: Diagnostic Utility of Upper Gastrointestinal Biopsies. Histopathology. Jul 2019;doi:10.1111/his.13963
- Badran YR, Cohen JV, Brastianos PK, Parikh AR, Hong TS, Dougan M. Concurrent therapy with immune checkpoint inhibitors and TNFα blockade in patients with gastrointestinal immune-related adverse events. J Immunother Cancer. Aug 2019;7(1):226. doi:10.1186/s40425-019-0711-0
- Chen ST, Molina GE, Lo JA, et al. Dermatology Consultation Reduces Interruption of Oncologic Management Among Hospitalized Patients with Immune-related Adverse Events: A Retrospective Cohort Study. J Am Acad Dermatol. Sep 2019;doi:10.1016/j.jaad.2019.09.026
- Criss SD, Mooradian MJ, Watson TR, Gainor JF, Reynolds KL, Kong CY. Cost-effectiveness of Atezolizumab Combination Therapy for First-Line Treatment of Metastatic Nonsquamous Non-Small Cell Lung Cancer in the United States. JAMA Netw Open. Sep 2019;2(9):e1911952. doi:10.1001/jamanetworkopen.2019.11952
- Dubey D, David WS, Amato AA, et al. Varied phenotypes and management of immune checkpoint inhibitor-associated neuropathies. Neurology. Sep 2019;93(11):e1093-e1103. doi:10.1212/WNL.0000000000008091
- Hughes MS, Zheng H, Zubiri L, et al. Colitis after checkpoint blockade: A retrospective cohort study of melanoma patients requiring admission for symptom control. Cancer Med. Sep 2019;8(11):4986-4999. doi:10.1002/cam4.2397
- Rubin KM, Hoffner B, Bullock AC. Caring for Patients Treated With Checkpoint Inhibitors for the Treatment of Metastatic Merkel Cell Carcinoma. Semin Oncol Nurs. Sep 2019:150924. doi:10.1016/j.soncn.2019.08.003
- Ganatra S, Parikh R, Neilan TG. Cardiotoxicity of Immune Therapy. Cardiol Clin. Nov 2019;37(4):385-397. doi:10.1016/j.ccl.2019.07.008
- Hughes MS, Molina GE, Chen ST, et al. Budesonide treatment for microscopic colitis from immune checkpoint inhibitors. J Immunother Cancer. 11 2019;7(1):292. doi:10.1186/s40425-019-0756-0
- Alvi RM, Frigault MJ, Fradley MG, et al. Cardiovascular Events Among Adults Treated With Chimeric Antigen Receptor T-Cells (CAR-T). J Am Coll Cardiol. 12 2019;74(25):3099-3108. doi:10.1016/j.jacc.2019.10.038
- Qualls D, Seethapathy H, Bates H, et al. Positron emission tomography as an adjuvant diagnostic test in the evaluation of checkpoint inhibitor-associated acute interstitial nephritis. J Immunother Cancer. 12 2019;7(1):356. doi:10.1186/s40425-019-0820-9
- Seethapathy H, Zhao S, Chute DF, et al. The Incidence, Causes, and Risk Factors of Acute Kidney Injury in Patients Receiving Immune Checkpoint Inhibitors. Clin J Am Soc Nephrol. 12 2019;14(12):1692-1700. doi:10.2215/CJN.00990119
- Agor J, Özaltın OY, Ivy JS, Capan M, Arnold R, Romero S. The value of missing information in severity of illness score development. J Biomed Inform. 2019;97:103255. doi:10.1016/j.jbi.2019.103255
- Durbin SM, Zubiri L, Niemierko A, et al. Clinical Outcomes of Patients with Metastatic Cancer Receiving Immune Checkpoint Inhibitors in the Inpatient Setting. Oncologist. 2021;26(1):49-55. doi:10.1002/onco.13561
- Karschnia P, Jordan JT, Forst DA, et al. Clinical presentation, management, and biomarkers of neurotoxicity after adoptive immunotherapy with CAR T cells. Blood. 2019;133(20):2212-2221. doi:10.1182/blood-2018-12-893396
- Thompson JA, Schneider BJ, Brahmer J, et al. Management of Immunotherapy-Related Toxicities, Version 1.2019. J Natl Compr Canc Netw. 2019;17(3):255-289. doi:10.6004/jnccn.2019.0013
- Criss SD, Mooradian MJ, Watson TR, Gainor JF, Reynolds KL, Kong CY. Cost-effectiveness of Atezolizumab Combination Therapy for First-Line Treatment of Metastatic Nonsquamous Non-Small Cell Lung Cancer in the United States. JAMA Netw Open. 2019;2(9):e1911952. Published 2019 Sep 4. doi:10.1001/jamanetworkopen.2019.11952
- Mahmood SS, Fradley MG, Cohen JV, et al. Myocarditis in Patients Treated With Immune Checkpoint Inhibitors. J Am Coll Cardiol. 04 2018;71(16):1755-1764. doi:10.1016/j.jacc.2018.02.037
- Ostvar S, Choi, J, Chu, J, Nipp, R, Dougan, M, Reynolds, K, Gainor, J, Kong, C, Hur, C. Cost effectiveness of single versus dual immune checkpoint blockade for chemotherapy-refractory esophageal, GE junction, and gastric cancers. American Society of Clinical Oncology Meeting June, 2018.
- Reynolds K, Cohen, J, Ryan, D, Hochberg, E, Dougan, M, Thomas, M, Guidon, A, Channick, C, Chen, S, Schoenfeld, S, Sise, M, Leaf, R, Neilan, T, Chu, J, Hur, C, Murciano-Goroff, Y, Villani, A, Nasrallah, M, Sullivan, R, Bardia, A. Severe immune-related adverse effects (irAE) requiring hospital admission in patients treated with immune checkpoint inhibitors for advanced malignancy: temporal trends and clinical significance. American Society of Clinical Oncology Meeting June, 2018.
- Ganatra S, Neilan TG. Immune Checkpoint Inhibitor-Associated Myocarditis. Oncologist. Aug 2018;23(8):879-886. doi:10.1634/theoncologist.2018-0130
- Mahmood SS, Sullivan RJ, Reynolds KL, Neilan TG. Reply: Immunosuppression Does Not Reduce Antitumor Efficacy. J Am Coll Cardiol. 08 2018;72(6):702. doi:10.1016/j.jacc.2018.06.005
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- Reynolds KL, Guidon AC. Diagnosis and Management of Immune Checkpoint Inhibitor Associated Neurologic Toxicity: Illustrative Case and Review of the Literature. Oncologist. Nov 2018;doi:10.1634/theoncologist.2018-0359
- Criss SD, Mooradian MJ, Sheehan DF, et al. Cost-effectiveness and Budgetary Consequence Analysis of Durvalumab Consolidation Therapy vs No Consolidation Therapy After Chemoradiotherapy in Stage III Non-Small Cell Lung Cancer in the Context of the US Health Care System. JAMA Oncol. 2019;5(3):358-365. doi:10.1001/jamaoncol.2018.5449
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In this interview series, Kerry Reynolds, MD, director of the SIC program, sits down with a SIC team member for a deeper-dive into their work.
- Yevgeniy Semenov, MD: Cutaneous Immune-Related Adverse Events
- Tom Neilan, MD and Zsofia Drobni, MD: Immune Checkpoint Inhibitor Therapy From a Cardiologist's Perspective
- Meghan Sise, MD: Renal Toxicities with Immune Checkpoint Inhibitors
- Leeann Burton, MD: Neurological Immune-Related Adverse Events
- Amanda Guidon, MD: Defining the Spectrum of Neurological Immune-Related Adverse Events
- Steven Chen, MD: Steroids for Treatment of Immune-Related Adverse Events
Facing Immunotherapy: A Guide for Patients and Their Families
Authored 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.
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