Immunotherapy Emergencies
•Descargar como PPTX, PDF•
1 recomendación•420 vistas
This document summarizes a presentation on cancer emergencies related to novel oncologic therapies like immunotherapy and CAR T-cell therapy. The presentation reviews immune-related adverse events from checkpoint inhibitors like diarrhea, colitis, and pneumonitis. It also discusses potential complications from CAR T-cell therapy including cytokine release syndrome, neurotoxicity, and HLH/MAS. The management of these complications is discussed including workup, medications, and disposition. Examples are provided of evaluation and treatment for immune-related colitis in a patient on checkpoint inhibitors.
Recomendados
Recomendados
Más contenido relacionado
La actualidad más candente
La actualidad más candente (20)
Similar a Immunotherapy Emergencies
Similar a Immunotherapy Emergencies (20)
Más de David Marcus
Más de David Marcus (16)
Último
Último (20)
Immunotherapy Emergencies
- 1. David A. Marcus, MD @EMIMDoc – EMIMDoc.org Residency Director, Combined Program in EM/IM+CC Northwell Health, NY EMIM Conference (Webex) - September 17, 2019
- 2. Review presentation, evaluation and management of Heme/Onc emergencies in the context of novel oncologic therapies. Learners: Remote participants EMIM, EM, IM Residents and Faculty Medical Students #EMIMconf
- 3. Cancer Emergencies Hemostasis RBC’s WBC’s Mass Effects Med Effects #EMIMconf
- 4. Immunotherapy - NEW SVC Syndrome Blast Crisis Neutropenic Fever Hyperviscosity Syndrome Tumor Lysis Syndrome Cord Compression And more… #EMIMconf
- 5. #EMIMconf
- 7. 68 year old F undergoing treatment for melanoma (Yervoy) p/w 3 days of abdominal pain, chills, diarrhea (5-6 daily). Has noted some blood streaked stool. Otherwise eating and drinking, and in USOH. Mild diffuse abd tenderness on exam, well appearing. TriageVitals: HR 88, BP 143/89, RR 10,T 99.0 What is your work up? What is the likely management and dispo? #EMIMconf
- 10. #EMIMconf
- 12. Ipilimumab (Yervoy) Nivolimumab (Opdivo) Pembrolizumab (Keytruda) Avelumab (Bavencio) Durvalumab (Imfinzi) #EMIMconf
- 13. Majzoub et al. Adverse Effects of Immune Checkpoint Therapy in Cancer Patients Visiting the Emergency Department of a Comprehensive Cancer Center. Ann Emerg Med. 2019;73:79-87 Native Med Med Native
- 14. Immune Related Adverse Events (irAE) Most common systems involved: GI (diarrhea, colitis, Hepatitis) Pulmonary (Pneumonitis) Skin (Various rashes, Sweet’s Syndrome,TEN, SJS) Endocrine (Hypohysitis, Hypothyroidism, Grave’s, Thyroid Storm, IDDM, Adrenal Insufficiency) #EMIMconf
- 15. Recent study in the Annals of EM (MD Anderson) 1026 visits by 628 pts on Checkpoint Inhibitors 66.5% overall admission rate 25% of visits due to irAE 81.7% admission rate for irAE visits Prevalence of irAE changes by agent Majzoub et al. Adverse Effects of ImmuneCheckpointTherapy in Cancer PatientsVisiting the Emergency Department of a Comprehensive Cancer Center.Ann Emerg Med. 2019;73:79-87. #EMIMconf
- 16. Based on: NationalCancer Institute's CommonTerminologyCriteria for Adverse Events (CTCAE), version 5
- 17. Grade 1/2 Symptomatic Mgm’t r/o infection +/- Prednisone 0.5-1 mg/kg Outpt Onc f/u Likely DC Grade 3/4 ABC’s/Resusc Emergent Onc Steroid* 1-2 mg/kg PossibleABx Admit, Possible ICU *Steroid: Prednisone or Methylprednisolone Based on: Brahmer et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American. Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018 June 10; 36(17): 1714–1768.
- 18. 68 year old F undergoing treatment for melanoma (Yervoy), with blood streaked stools, mild tenderness. What is your work up? Sepsis panel, C. diff, GI PCR, O&P; Get PR temp Obtain CTAP? What is the likely management and dispo? Grade 2 colitis IV Fluids, pain control if needed Discuss with Heme/Onc, possible Prednisone 1 mg/kg, possible Loperamide Possible discharge #EMIMconf
- 20. Tisagenlecleucel (Kymriah) Axicabtageneciloleucel (Yescarta) Llanfairpwllgwyngyllgogerychwyrndrobwlllla ntysiliogogogoch (Welsalta) St Mary's Church in the Hollow of theWhite Hazel near a RapidWhirlpool and the Church of St.Tysilio near the Red Cave #EMIMconf
- 21. #EMIMconf
- 23. Cytokine Release Syndrome (majority of pts get this; within 3 days; usually admitted for infusion, less likely in ED) Neurotoxicity+CRES (CART Related Encephalopathy Syndrome), may be 8 wks or more after infusion ON target/OFF tumor Immunosuppression/Neutropenia Fulminant HLH/MAS #EMIMconf
- 24. Highly variable ABCs/Resuscitation Emergent Heme/Onc Consult Generally immunosuppressed – GiveAbx Possibly steroids Possibly Etoposide PossiblyTocilizumab (IL6 receptor MAB) for critically ill CAR-T CRS #EMIMconf
- 25. Checkpoint Inhibitors Take the brakes off ofT cells irAE are generally inflammatory Not necessarily immunosuppressed Staging, Management CAR-T ChimericT cells target tumor antigen Variable irAE Complex management Often immunosuppressed #EMIMconf
- 27. Hematologic emergencies may be very subtle When immunotherapy is involved, think immune activation, not suppression Initiate a broad evaluation: CBC + diff CompVBG CMP+Mg+Phos(+Uric Acid if indicated) Blood cultures? Imaging may be necessary Get some advice… #EMIMconf
- 28. Based on: NationalCancer Institute's CommonTerminologyCriteria for Adverse Events (CTCAE), version 5
- 29. Grade 1/2 Symptomatic Mgm’t r/o infection +/- Prednisone 0.5-1 mg/kg Outpt Onc f/u Likely DC Grade 3/4 ABC’s/Resusc Emergent Onc Steroid* 1-2 mg/kg PossibleABx Admit, Possible ICU *Steroid: Prednisone or Methylprednisolone Based on: Brahmer et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American. Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018 June 10; 36(17): 1714–1768.
- 30. References/Additional Reading • Brahmer et al. Management of Immune-RelatedAdverse Events in PatientsTreatedWith ImmuneCheckpoint InhibitorTherapy: American. Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018 June 10; 36(17): 1714–1768. • Doyle, C. Immunotherapy-RelatedToxicities May Be More CommonThan Originally Reported.TheASCO Post. Accessed online: August 10, 2019. https://www.ascopost.com/issues/december-25-2018/immunotherapy-related- toxicities-may-be-more-common-than-originally-reported/ • Kroschinsky, etal. New drugs, new toxicities: severe side effects of modern targeted and immunotherapy of cancer and their management. Crit Care. 2017Apr 14;21(1):89 • Majzoub et al. Adverse Effects of ImmuneCheckpointTherapy in Cancer PatientsVisiting the Emergency Department of a Comprehensive Cancer Center. Ann Emerg Med. 2019;73:79-87 • National Cancer Institute.CommonTerminology Criteria for Adverse Events (CTCAE) ,Version 5. November 27, 2017. Accessed online: https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_50 • Pallin, DJ, et al. Immune-relatedAdverse Events inCancer Patients.Academic Emergency Medicine. 2018;25:819–827. • Simmons D, Lang E (October 13, 2017)The Most RecentOncologic Emergency:What Emergency Physicians Need to Know About the Potential Complications of ImmuneCheckpoint Inhibitors. Cureus. 9(10): e1774. DOI 10.7759/cureus.1774 • Srivastava, A. Immunotherapy Complications in the Emergency Department: Be on the Lookout for theCheckpoints! Critical Care Section Update,AAEM. Published in: Common Sense; November, 2018.
Notas del editor
- Too much or too little of each, abnormalities of each. This talk will focus only on AE associated with immunotherapy
- Patients with known or suspected malignancy
- Take these patients seriously, high index of suspicion needed. You will miss important Dx otherwise. Can be subtle.
- Successful so far (though some mixed outcomes) and AE thought to be less common/less severe than traditional chemo Checkpoint: Metastatic Melanoma: > 50% increases in mean survival and 2 year survival NSCLC: Similar benefits Head and neck Squamous Cell CA Renal Cell Carcinoma Urothelial Carcinoma (bladder) Hodgkin’s Lymphoma CAR-T ALL Large B Cell Lymphoma Reference Landscape of Immunotherapy/Nixon article for numbers (Current Oncology 2018)
- Traditional chemo = nuking the body!
- Indiscriminate poisoning vs tailor made solutions
- Checkpoint inhibitors vs chimera
- 3 main mechanisms for CI’s Enhancing T cell activation (CD28/CTLA4) Preventing T cell inactivation (PD-1 (on CD8 cells) Inhibitors) – prevent binding to the inactivating ligand PD-L1 Preventing T cell inactivation(PD-L1 inhibitors) (inactivates the CD8 cells, can be upregulated by tumor cells; blocked by CI) – block the ligand itself
- Sweet's syndrome (SS), or acute febrile neutrophilic dermatosis is a skin disease characterized by the sudden onset of fever, an elevated white blood cell count, and tender, red, well-demarcated papules and plaques that show dense infiltrates by neutrophil granulocytes on histologic examination. Discuss relative frequencies – 3% - 30% - Several, including Hypophysitis, have been shown to be more common in practice than on validations.
- AND MOST IMPORTANTLY THE MGMT IS DIFFERENT.
- Based on: National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5 Grade 5 AE for all = DEATH! THESE MAY BE SUBACUTE OR EVEN DELAYED IN ONSET (WEEKS-MONTHS OUT)
- Checkpoint inhibitors vs chimera
- Why? Seems to have very good cure/remission rates – though high risk.
- Hemophagocytic lymphohistiocytosis (HLH) CRS – fever, hypotension, tachycardia, lab abnormalities (hypoK, renal insufficiency, CRP, procalcitonin), MAY MIMIC ANAPHYLAXIS
- Etoposide – arrests cells in late S phase or early G2 phase. Possibly via mitochondrial transport inhibition. Topoisomerase II Inhibitor
- Based on: National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5 Grade 5 AE for all = DEATH! THESE MAY BE SUBACUTE OR EVEN DELAYED IN ONSET (WEEKS-MONTHS OUT)