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Immunotherapy and Heme/Onc Emergencies for Emergency Medicine

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A primer on Immunotherapy, SVC Syndrome, and Blast Crisis for Emergency Medicine resident physicians. Delivered May 15, 2019. #EMconf

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Immunotherapy and Heme/Onc Emergencies for Emergency Medicine

  1. 1. David A. Marcus, MD @EMIMDoc – EMIMDoc.org Zucker-NSLIJ #Emconf @PJI May 15, 2019
  2. 2.  Review presentation, evaluation and management of Heme/Onc emergencies  Learners:  EM Residents of all years  Rotating senior medical students
  3. 3. Cancer Emergencies Hemostasis RBC’s WBC’s Mass Effects Med Effects
  4. 4. Found at: https://lancasteronline.com/navigating-cancer-s-emotional-impact/article_e68d2734-78da-11e5-8070-0f45f800abd5.html
  5. 5.  Immunotherapy - NEW  SVC Syndrome  Blast Crisis  Covered Previously  Neutropenic Fever  Hyperviscosity Syndrome  Tumor Lysis Syndrome  CordCompression
  6. 6.  57 year old F with long smoking history states that she has been feeling tired lately. Noticed she appears flushed sometimes.  Has been having worsening DOE and states people have told her that she looks differently, something about her facial features.
  7. 7. Not Really, this is her… https://casereports.bmj.com/content/2018/bcr-2018-225220
  8. 8.  Classically:  Dyspnea, Facial Swelling, Upper Extremity Swelling.  Stokes’ Sign  Pemberton Sign  Sx worse with bending over (Bendopnea)  Less commonly:  Cough, chest pain  Eventually:  Plethora, severe upper swelling, JVD, Cyanosis https://emergencymedicinecases.com/episode-33-oncologic-emergencies/ https://annals.org/aim/fullarticle/710037/pemberton-sign
  9. 9.  Classically:  Dyspnea, Facial Swelling, Upper Extremity Swelling.  Stokes’ Sign  Pemberton Sign  Sx worse with bending over (Bendopnea)  Less commonly:  Cough, chest pain  Eventually:  Plethora, severe upper swelling, JVD, Cyanosis https://emergencymedicinecases.com/episode-33-oncologic-emergencies/ https://annals.org/aim/fullarticle/710037/pemberton-sign
  10. 10.  Classically:  Dyspnea, Facial Swelling, Upper Extremity Swelling.  Stokes’ Sign  Pemberton Sign  Sx worse with bending over (Bendopnea)  Less commonly:  Cough, chest pain  Eventually:  Plethora, severe upper swelling, JVD, Cyanosis https://emergencymedicinecases.com/episode-33-oncologic-emergencies/ https://annals.org/aim/fullarticle/710037/pemberton-sign
  11. 11. Most Commonly  Lung CA (especially apical)  Other:  Goiter, pericardial constriction, primary thrombosis, aneurysm, indwelling catheter,  other mechanical obstructions Mimics  CHF  Tamponade
  12. 12.  Management  Emergent Rad-Onc consult  Chemo  Stenting  Anticoagulation if indicated  AW management if needed  Prognosis  25% survival at 1 year
  13. 13.  61 year old M with h/o CML, HTN, DM, CAD/stent who p/w LUQ abd pain and chills x 2 days. She is ill appearing but in NAD. Has LUQ tenderness, no guarding. Generalized body tenderness.  TriageVitals: HR 92, BP 160/89, RR 14,T 101.0  What is your work up?  What is the likely management and dispo?
  14. 14.  WBC 42  Blasts 30%  H/H: 8/24  Platelets: 105  Urines: +Nitrite,WBC 10-25k, +LE  What is the likely management and dispo?  Broad spectrum antibiotics, IV Fluids  Heme/Onc consult  Admit for Blast Crisis
  15. 15. Making the diagnosis  ElevatedWBC, Blasts > 20%  Pancytopenia, functionally neutropenic  May present septic or with non specific sx  Bone pains often present  May present with stroke, MI,VTE symptoms  Sometimes: Priapism, bowel infarctions, limb ischemia, renal insufficiency
  16. 16.  Broad spectrum antibiotics  IV fluids  Use caution with PRBC  May hemorrhage, may need platelets  Leukostasis (often withWBC > 50) may require Leukophoresis  Emergent Heme/Onc Consult  MICU?
  17. 17.  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 streaking. 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?
  18. 18. EnhancedT-Cell Function IncreasedTumor Cell Death CAR-T
  19. 19.  Ipilimumab (Yervoy)  Nivolimumab (Opdivo)  Pembrolizumab (Keytruda)  Avelumab (Bavencio)  Durvalumab (Imfinzi)
  20. 20. 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
  21. 21. Immune Related Adverse Events  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)
  22. 22. Recent study in theAnnals of EM (MD Anderson)  1026 visits by 628 pts on CI’s  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.
  23. 23. Based on: NationalCancer Institute's CommonTerminologyCriteria for Adverse Events (CTCAE), version 5
  24. 24. 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.
  25. 25.  68 year old F undergoing treatment for melanoma (Yervoy), found to have colitis.  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
  26. 26.  Tisagenlecleucel (Kymriah)  Axicabtageneciloleucel (Yescarta)  Llanfairpwllgwyngyllgogerychwyrndrobwllllan tysiliogogogoch (Welsalta) St Mary's Church in the Hollow of theWhite Hazel near a RapidWhirlpool and the Church of St.Tysilio near the Red Cave
  27. 27. https://medium.com/@yx2017be/cancer-immunotherapy-and-car-t-cell-therapy-d4b772a5d2f5
  28. 28. 3 weeks https://www.onclive.com/publications/oncology-live/2018/vol-19-no-12/car-tcell-therapy-the-sticker-price-is-just-for-openers
  29. 29.  Cytokine Release Syndrome (majority of pts get this; within 3 days; usually admitted for infusion anyway, 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
  30. 30. Highly variable  ABCs/Resuscitation  Emergent Heme/Onc Consult  Generally immunosuppressed – GiveAbx  Possibly steroids  Possibly Etoposide
  31. 31.  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
  32. 32. http://www.newstimes.co.uk/i-survived-and-so-did-i-mothers-raw-photos-show-what-its-like-to-have-breast-cancer-while-pregnant/
  33. 33.  Hematologic emergencies may be very subtle  Maintain a high index of suspicion  Send broad labs:  CBC + diff  CompVBG  CMP+Mg+Phos(+Uric Acid if indicated)  Get some advice…
  34. 34. Based on: NationalCancer Institute's CommonTerminologyCriteria for Adverse Events (CTCAE), version 5
  35. 35. 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.
  36. 36. Online Checkpoint Inhibitor Toolkit (Cancer Care Ontario): https://www.cancercareontario.ca/en/guidelines-advice/modality/immunotherapy/immune- therapy-toolkit Cited Works: • Azim, A. New OncologicTherapies Mean NewOncologic Emergencies: An Approach to Immunotherapy-RelatedAdverse Events. MedicalConcepts Case Series, CanadiEM.Accessed online May 10, 2019. https://canadiem.org/an-approach-to-immunotherapy- related-adverse-events/ • Ballard D,Vinson D. MedicallyClear: New Immunotherapy Revolutionizes Cancer Care but GuessWhere Adverse Events End Up? Emergency Medicine News: Sept 2018 – 40(9): 29.Accessed online May 10, 2019. https://journals.lww.com/em- news/pages/articleviewer.aspx?year=2018&issue=09000&article=00015&type=Fulltext#pdf-link • Brahmer et al. Management of Immune-Related Adverse Events in PatientsTreatedWith Immune Checkpoint InhibitorTherapy: American. Society of ClinicalOncology Clinical PracticeGuideline. J Clin Oncol. 2018 June 10; 36(17): 1714–1768. • Doyle C. Immunotherapy-RelatedToxicities May Be More CommonThan Originally Reported.TheASCO Post. December 25, 2018. Accessed online May 10, 2019. https://www.ascopost.com/issues/december-25-2018/immunotherapy-related-toxicities-may-be-more- common-than-originally-reported/ • Majzoub et al. Adverse Effects of Immune CheckpointTherapy in Cancer PatientsVisiting the Emergency Department of a Comprehensive Cancer Center.Ann Emerg Med. 2019;73:79-87. • Nixon et al. Current landscape of immunotherapy in the treatment of solid tumours, with future opportunities and challenges. Curr Oncol. 2018Oct; 25(5): e373–e384. • Palin et al. Immune-relatedAdverse Events in Cancer Patients.Academic Emergency Medicine. 2018;25:819–827 • Simmons D, Lang E (October 13, 2017)The Most Recent Oncologic Emergency:What Emergency Physicians Need to KnowAbout the PotentialComplications of Immune Checkpoint Inhibitors.Cureus 9(10): e1774. DOI 10.7759/cureus.1774 • Srivastava,A. Immunotherapy Complications in the Emergency Department: Be on the Lookout for theCheckpoints! AAEMCritical Care Medicine Section Report. Common Sense November/December 2018.

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