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

1. David A. Marcus, MD
@EMIMDoc – EMIMDoc.org
Zucker-NSLIJ #Emconf @PJI
May 15, 2019

2.  Review presentation, evaluation and
management of Heme/Onc emergencies
 Learners:
 EM Residents of all years
 Rotating senior medical students

3. Cancer Emergencies
Hemostasis
RBC’s
WBC’s
Mass Effects Med Effects

4. Found at: https://lancasteronline.com/navigating-cancer-s-emotional-impact/article_e68d2734-78da-11e5-8070-0f45f800abd5.html

5.  Immunotherapy - NEW
 SVC Syndrome
 Blast Crisis
 Covered Previously
 Neutropenic Fever
 Hyperviscosity Syndrome
 Tumor Lysis Syndrome
 CordCompression

7.  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.

8. Not Really, this is her…
https://casereports.bmj.com/content/2018/bcr-2018-225220

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.  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.  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

12. Most Commonly
 Lung CA (especially apical)
 Other:
 Goiter, pericardial constriction, primary thrombosis,
aneurysm, indwelling catheter,
 other mechanical obstructions
Mimics
 CHF
 Tamponade

13.  Management
 Emergent Rad-Onc consult
 Chemo
 Stenting
 Anticoagulation if indicated
 AW management if needed
 Prognosis
 25% survival at 1 year

15.  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?

16.  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

17. 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

18.  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?

20.  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?

24. EnhancedT-Cell Function
IncreasedTumor Cell Death
CAR-T

25.  Ipilimumab (Yervoy)
 Nivolimumab (Opdivo)
 Pembrolizumab (Keytruda)
 Avelumab (Bavencio)
 Durvalumab (Imfinzi)

26. 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

27. 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)

28. 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.

29. Based on: NationalCancer Institute's CommonTerminologyCriteria for Adverse Events (CTCAE), version 5

30. 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.

31.  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

33.  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

34. https://medium.com/@yx2017be/cancer-immunotherapy-and-car-t-cell-therapy-d4b772a5d2f5

35. 3 weeks
https://www.onclive.com/publications/oncology-live/2018/vol-19-no-12/car-tcell-therapy-the-sticker-price-is-just-for-openers

36.  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

37. Highly variable
 ABCs/Resuscitation
 Emergent Heme/Onc Consult
 Generally immunosuppressed – GiveAbx
 Possibly steroids
 Possibly Etoposide

38.  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

39. http://www.newstimes.co.uk/i-survived-and-so-did-i-mothers-raw-photos-show-what-its-like-to-have-breast-cancer-while-pregnant/

40.  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…

41. Based on: NationalCancer Institute's CommonTerminologyCriteria for Adverse Events (CTCAE), version 5

42. 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.

43. 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.