Mass General Cancer Center's Dr. Kerry Reynolds discusses the management of toxicities in an inpatient setting. This video was recorded on May 18, 2019 at the Annual Advances in Cancer Immunotherapy CME Course.
Severe Immunotherapy Complications Service
Severe Immunotherapy Complications Service and Clinical-Translational Research Effort Program
Support Our Effort
Your gift to the Severe Immunotherapy Complications Service and Clinical-Translational Research Effort Program 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.
A First-of-its Kind Program
The Severe Immunotherapy Complications (SIC) Service and Clinical-Translational Research Effort Program, 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 Effort Program's multidisciplinary team of clinicians and researchers.
- Schoenfeld SR, Aronow ME, Leaf RK, Dougan M, Reynolds KL. Diagnosis and Management of Rare Immune-Related Adverse Events. Oncologist. Jan 2020;25(1):6-14. doi:10.1634/theoncologist.2019-0083
- Awadalla M, Mahmood SS, Groarke JD, et al. Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis. J Am Coll Cardiol. Feb 2020;75(5):467-478. doi:10.1016/j.jacc.2019.11.049
- Strohbehn IA, Lee M, Seethapathy H, et al. Safety and Efficacy of Immune Checkpoint Inhibitors in Patients on Dialysis: A Retrospective Case Series. Am J Kidney Dis. Aug 2020;76(2):299-302. doi:10.1053/j.ajkd.2020.02.451
- Darnell EP, Mooradian MJ, Baruch EN, Yilmaz M, Reynolds KL. Immune-Related Adverse Events (irAEs): Diagnosis, Management, and Clinical Pearls. Curr Oncol Rep. 03 2020;22(4):39. doi:10.1007/s11912-020-0897-9
- Molina GE, Yu Z, Foreman RK, Reynolds KL, Chen ST. Generalized bullous mucocutaneous eruption mimicking Stevens-Johnson syndrome in the setting of immune checkpoint inhibition: A multicenter case series. J Am Acad Dermatol. Mar 2020;doi:10.1016/j.jaad.2020.03.029
- Petrillo LA, El-Jawahri A, Nipp RD, et al. Performance status and end-of-life care among adults with non-small cell lung cancer receiving immune checkpoint inhibitors. Cancer. Mar 2020;doi:10.1002/cncr.32782
- Reynolds KL, Sullivan RJ, Fintelmann FJ, Mansour MK, England J. Case 9-2020: A 64-Year-Old Man with Shortness of Breath, Cough, and Hypoxemia. N Engl J Med. Mar 2020;382(12):1150-1159. doi:10.1056/NEJMcpc1909621
- Dubey D, David WS, Reynolds KL, et al. Severe Neurological Toxicity of Immune Checkpoint Inhibitors: Growing Spectrum. Ann Neurol. 05 2020;87(5):659-669. doi:10.1002/ana.25708
- Sullivan RJ, Johnson DB, Rini BI, et al. COVID-19 and immune checkpoint inhibitors: initial considerations. J Immunother Cancer. 05 2020;8(1)doi:10.1136/jitc-2020-000933
- Zhang L, Awadalla M, Mahmood SS, et al. Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis. Eur Heart J. May 2020;41(18):1733-1743. doi:10.1093/eurheartj/ehaa051
- Zhang L, Zlotoff DA, Awadalla M, et al. Major Adverse Cardiovascular Events and the Timing and Dose of Corticosteroids in Immune Checkpoint Inhibitor-Associated Myocarditis. Circulation. Jun 2020;141(24):2031-2034. doi:10.1161/CIRCULATIONAHA.119.044703
- Molina GE, Reynolds KL, Chen ST. Diagnostic and therapeutic differences between immune checkpoint inhibitor-induced and idiopathic bullous pemphigoid: a cross-sectional study. Br J Dermatol. Jun 2020;doi:10.1111/bjd.19313
- Badran YR, Shih A, Leet D, et al. Immune checkpoint inhibitor-associated celiac disease. Immunother Cancer. 06 2020;8(1)doi:10.1136/jitc-2020-000958
- Gupta S, Seethapathy H, Strohbehn IA, et al. Acute Kidney Injury and Electrolyte Abnormalities After Chimeric Antigen Receptor T-Cell (CAR-T) Therapy for Diffuse Large B-Cell Lymphoma. Am J Kidney Dis. Jul 2020;76(1):63-71. doi:10.1053/j.ajkd.2019.10.011
- Johnson DB, Reynolds KL, Sullivan RJ, et al. Immune checkpoint inhibitor toxicities: systems based approaches to improve patient care and research. Lancet Oncol. 08 2020;21(8):e398-e404. doi:10.1016/S1470-2045(20)30107-8
- Francis JH, Jaben K, Santomasso BD, et al. Immune Checkpoint Inhibitor-Associated Optic Neuritis. Ophthalmology. 2020;127(11):1585-1589. doi:10.1016/j.ophtha.2020.05.003
- Dougan M. Gastrointestinal and Hepatic Complications of Immunotherapy: Current Management and Future Perspectives. Curr Gastroenterol Rep. 2020;22(4):15. Published 2020 Mar 17. doi:10.1007/s11894-020-0752-z
- 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
- 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 ConsequenceAnalysis 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
- 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
- Neilan TG, Rothenberg ML, Amiri-Kordestani L, et al. Myocarditis Associated with Immune Checkpoint Inhibitors: An Expert Consensus on Data Gaps and a Call to Action. Oncologist. 08 2018;23(8):874-878. doi:10.1634/theoncologist.2018-0157
- Awadalla M M, S, Reynolds, K, Cohen, J, Sullivan, R, Shah, S, Picard, M, Lawrence, D, et al, Neilan, T. Global Longitudinal Strain and Myocarditis with Immune Checkpoint Inhibitors. Global Cardio-Oncology Summit September 2018.
- Faje AT, Lawrence D, Flaherty K, et al. High-dose glucocorticoids for the treatment of ipilimumab-induced hypophysitis is associated with reduced survival in patients with melanoma. Cancer. 09 2018;124(18):3706-3714. doi:10.1002/cncr.31629
- Mooradian M, Gainor, J, Dagogo-Jack, I, Reynolds, K. Immune-related adverse events: The Growing Pains of Immunoncology. International Association for the Study of Lung Cancer World Conference September, 2018.
- Schoenfeld S, Aronow, M, Karp, R, Dougan, M, Reynolds, K. Rare immune-related Adverse Events (irAEs): Diagnosis and Management. Oncologist 2018.
- Reynolds K, Thomas M, Dougan M. Diagnosis and Management of Hepatitis in Patients on Checkpoint Blockade. Oncologist. 09 2018;23(9):991-997. doi:10.1634/theoncologist.2018-0174
- 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
- Mooradian MJ, Sullivan RJ. Immunomodulatory effects of current cancer treatment and the consequences for follow-up immunotherapeutics. Future Oncol. 2017;13(18):1649-1663. doi:10.2217/fon-2017-0117
- Thebeau M, Rubin K, Hofmann M, Grimm J, Weinstein A, Choi JN. Management of skin adverse events associated with immune checkpoint inhibitors in patients with melanoma: A nursing perspective. J Am Assoc Nurse Pract. 2017;29(5):294-303. doi:10.1002/2327-6924.12458
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.
- Mar | 1 | 2019
The challenge of immunotherapy side effects spurs clinicians and researchers at Mass General to find new and better ways to care for cancer patients.
- Nov | 5 | 2019
Over the last decade, immunotherapies have increasingly offered hope to thousands of patients with cancer; however, this does not come without its adverse events (AEs), according to Kerry Reynolds, MD.
- Nov | 15 | 2019
Massachusetts General Hospital in Boston established its immunotherapy toxicity service care team in part because of the experience of David M., a patient treated there for metastatic melanoma that spread to the lung and brain.