Overview of Immunotherapy Related Adverse Event (irae) Management

Transcription

1 Overview of Immunotherapy Related Adverse Event (irae) Management DR. ROLAND LEUNG MEDICAL ONCOLOGY DEPARTMENT OF MEDICINE THE UNIVERSITY OF HONG KONG QUEEN MARY HOSPITAL

2 Outline Immune system overview Discuss the pathophysiology of IRAE Discuss how to monitor for IRAE in the clinic

3 From: Environmental immune disruptors, inflammation and cancer risk Carcinogenesis. 2015;36(Suppl_1):S232-S253. doi: /carcin/bgv038 Carcinogenesis The Author Published by Oxford University Press. All rights reserved. For Permissions, please

4 History of Cancer Immunotherapy 2011 Anti-CTLA4 approved for advanced melanoma 2010 First cellular immunotherapy approved for prostate cancer 2014 CAR T-cell therapy for hemat. malignancy

5 情報人員 指揮官 彈藥工廠 / 庫 追擊手 通訊 / 密碼 彈藥 National Cancer Institute 監管

6 情報人員 指揮官 彈藥工廠 / 庫 追擊手 通訊 / 密碼 彈藥 National Cancer Institute 監管

7 2015 by American Association for Cancer Research Amani Makkouk, and George J. Weiner Cancer Res 2015;75:5-10

8 Immune response cycle Check Point Inhibitors Immunity , p. 1-10

9 Normal use of PDL-1 Inaguma et al Am J Surg Pathol Aug; 40(8):

10 Current FDA-approved indications for immune checkpoint inhibitor Melanoma (March 2011 CTLA 4, Sept 2014 Anti PD-1) Non-small cell lung cancer (March 2015 Anti PD-1 Oct 2016 Anti PD-L1) Renal cell carcinoma (Nov 2015 Anti PD-1 Anti PD-1with CTLA4 April 2018) Classical Hodgkin Lymphoma (May 2016 Anti PD-1) Bladder cancer (May 2016 Anti PD-1 April 2017 Anti PDL-1) Head and neck cancer (Aug 2016 Anti PD-1) MSI-H/dMMR solid tumors (May 2017 Anti PD-1) Gastric cancer (Sept 2017 Anti PD-1) Hepatocellular carcinoma (Sept 2017Anti PD-1) Small Cell Lung Cancer (Sept 2018)

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14 Weber JS et al Oncologist July

15 Weber JS et al Oncologist July

16 Main Immune-Related Toxicities IrAEs Cutaneous rash/pruritus Toxic epidermal necrolysis Endocrine pituitary, thyroid, adrenal Hepatic transaminitis Kinetics of Immune-Related Toxicities Hypophysitis and endocrinopathy occasionally can occur after cessation of immunotherapy Hepatic failure Lung asymptomatic Fatal pneumonitis Gastro-intestinal diarrhoea Colitis/bowel perforation Others Rheumatological arthritis, psoriasis Ophthalmic episcleritis, uveitis Neurological peripheral neuropathy -> Guillain-Barré syndrome

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18 General approach for suspected iraes Routine monitoring: General Pruritus, malaise System-related Endocrine dysfunction (Thyroid, low cortisol) -> TFT/morning cortisol +/- short synacthen test Rash Pneumonitis -> CXR Colitis Hepatitis -> LFT Nephritis -> RFT, urine for protein Precaution: existing autoimmune disorders High suspicion and early diagnosis Communication with treating doctor Rapid use of steroid / immune suppressants iimmunotherapy

19 Skin toxicity Blepharoconjunctivitis Pruritic maculopapular rash (extremities, trunk) Hemorrhagic crusting of lip Toenail toxicity Peeling of skin & desquamation Case Rep Oncol 2016; 9: ; ASCO post Oct 2013 Vitiligo

20 Management of skin toxicity Annals of Oncology (Suppl 4) iv119 v142, 2017

21 Frame work for follow up for IRAE Organ System History(Symptoms) Examination (Signs) Investigations (Labs, Xray etc ) Skin Rash, blister, Dry eyes, Dry mucosa, colour change, hair loss Rash, blister, ulcers, vitiligo, alopecia Cardiac Palpitation, ET, SOB, Orthopnea Dysrhythmia, Murmur, Heart failure ECG, CXR, ECHO

22 Summary Immunotherapy is the next generation cancer treatment Potential for cure or prolonged response but only if they don t succumb to IrAEs Anti-PD1 Anti-PDL1 Ab are in general well tolerated Anti-CTLA4 is associated more higher grade toxicities Awareness in still low in most hospitals Patient education and a dedicated team for monitoring of toxicities is utmost important These are out-patient events Use of immunosuppressant for iraes would not impair the treatment response We are only at the beginning with 2 classes of drugs. Its time to make friends with other specialties

23 Beginning of a Cure for Cancer?