Why is it different Why is it important Dr Avinash Gupta Consultant in Medical Oncology Melanoma Team Christie NHS Foundation Trust The Era of Immunotherapy Cancer Type Approved Immunotherapy ID: 910341
Download Presentation The PPT/PDF document "Immuno-Oncology Adverse Event Management" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Immuno-Oncology Adverse Event Management Why is it different? Why is it important?
Dr Avinash Gupta
Consultant in Medical Oncology
Melanoma Team – Christie NHS Foundation Trust
Slide2The Era of ImmunotherapyCancer TypeApproved Immunotherapy DrugMelanoma
Ipilimumab
,
Nivolumab, PembrolizumabLung cancerNivolumab, PembrolizumabRenal cancerNivolumabUrothelial cancerNivolumab, Pembrolizumab, Atezolizumab, Avelumab, DurvalumabHodgkins’s lymphomaNivolumab, PembrolizumabHead & Neck cancerNivolumabMerkel cell cancerAvelumab
CTLA-4 inhibitor PD-1 inhibitor PDL-1 inhibitor
Generally administered intravenously every 2-3 weeks
Slide3CTLA4
CD28
B7
T-cell proliferation,
differentiation
and survival
T - cell
APC
Signal 1
Signal 2
MHC
TCR
Ag
B
T - cell
APC
Signal 1
Signal 2
MHC
TCR
Ag
CTLA4
CD28
B7
A
T - cell
APC
Signal 1
Signal 2
MHC
TCR
Ag
C
T-cell downregulation
and functional
inactivation
Restoration of
T-cell proliferation,
differentiation and survival
Ipilimumab
CD28
CTLA4
B7
Figure 1.
A: Activation of T-cells requires 2 signals; presentation of antigen to TCR by MHC and interaction between co-stimulatory molecule B7 and CD28. B: T-cell activation
upregulates
CTLA4, which binds to B7 with greater affinity than CD28 and blocks signal 2, thus down-regulating the T-cell. C: Anti-CTLA4 antibodies bind and block CTLA4, thus allowing resumption of signal 2 and restoration of T-cell activation.
APC – Antigen Presenting Cell, MHC – Major Histocompatibility Complex, TCR – T-cell receptor, Ag – Antigen, B7 – peripheral membrane protein, CTLA4 – Cytotoxic T Lymphocyte Antigen 4, CD – Cluster of Differentiation
Mechanism
of action of
ipilimumab
Slide4B7
Resting
T - cell
Antigen Presenting cell
Co-stimulatory signal
MHC
TCR
Ag
CD28
PD-1
PDL-1/PDL-2
Inhibitory signal
Tumour cell
PDL-1
PD-1
Inhibitory signals
B7
Active
T - cell
Antigen Presenting cell
Co-stimulatory signal
MHC
TCR
Ag
B
CD28
PD-1
PDL-1/PDL-2
Inhibitory signal
Tumour cell
PDL-1
PD-1
Inhibitory signals
PD-1 / PDL-1 inhibitors
PD-1 / PDL-1 inhibitors
A
Mechanism of action of PD1/PDL1 inhibitors
Slide5Patients with unresectable Stage III or Stage IV melanoma
Overall Survival with Combined
Nivolumab
and Ipilimumab in Advanced MelanomaWolchok, NEJM, 2017; 377: 1345-1356BENEFIT
Slide6Overall Survival with Combined Nivolumab and Ipilimumab
in Advanced Melanoma
Wolchok
, NEJM, 2017; 377: 1345-1356RISK
Slide7Time to onset of grade 3-4 toxicity
ESMO
Clinical Practice Guidelines for
management of toxicities from immunotherapy.Ann Oncol. 2017;28(suppl_4):iv119-iv142. doi:10.1093/annonc/mdx225
Slide8Current Patient Pathway for AEs
Patient/Carer
Patient/Carer
Primary and Community Care
24 Hour Advice Lines
Urgent Care
ED/AMU
Acute Oncology Services
Key points
111 and 999 Services
Slide9Christie - Acute Oncology Service
Specially trained AO nurses with clinical experience
Accredited triage scoring system
Liaise with relevant medical, nursing & research teamsProvide advice to GPs alsoaccess to patient notes, calls documented & notes updatedIf URGENT & cannot admit to OAU– info & guidance provided to A&E staff & AO staff notifiedEach hospital has it’s ownAO consultant & nurses Outpatient clinicsEmergency referrals from other hospitals/outreach sitesA consultant led & delivered serviceWorking collaboratively with oncologists
Daily OAU ward round for all patients
Slide1024 Hour Advice Lines
24 Hour Advice Lines - primary function to provide telephone assessment and triage for patients who are receiving or have received non surgical anti-cancer treatment
Also provide advice for professionals
Usually use the UKONS 24 Hour Triage Tool (a common language shared across boundaries)UKONS guidelines for managing immune-related toxicity being drafted…
Slide1124 Hour Advice Lines
24 Hour Advice Lines - primary function to provide telephone assessment and triage for patients who are receiving or have received non surgical anti-cancer treatment
Also provide advice for professionals
Usually use the UKONS 24 Hour Triage Tool (a common language shared across boundaries)UKONS guidelines for managing immune-related toxicity being drafted…
Slide12ESMO guidelines for managing
diarrhoea
/colitis
ESMO Clinical Practice Guidelines for management of toxicities from immunotherapy.Ann Oncol. 2017;28(suppl_4):iv119-iv142. doi:10.1093/annonc/mdx225
Slide13ESMO guidelines for managing pneumonitis
ESMO
Clinical Practice Guidelines for
management of toxicities from immunotherapy.Ann Oncol. 2017;28(suppl_4):iv119-iv142. doi:10.1093/annonc/mdx225
Slide14Patient presents unwell on/previously treated with immunotherapyTHINK IMMUNE – RELATED TOXICITYExclude possible infective causesDiarrhoea: viral/bacterial gastroenteritis, C. Diff, CMVSOB/Cough: LRTI, PCPArrange key investigationsFBC, U&Es, LFTs, TFTs, baseline cortisol (9am if possible, else random)Other pituitary axis bloods: ACTH, LH/FSH, prolactinAXR, CT
abdo
/pelvis,
sigmoidoscopy/colonoscopy (with biopsies to look for colitis and CMV infection)CXR, HRCT chest, PCP tests, Lung function tests, bronchoscopy + BALLiver screen, renal screen, etc…Have low threshold for starting high dose steroids (and taper slowly)Discuss with local Acute Oncology Service / Christie Hotline / Oncology SpR/Consultant on callKey Points
Slide15Increasing use of immunotherapy across multiple tumour typesSigns and symptoms of toxicity are different to chemotherapyirAEs occur even after finishing treatmentKey issuesExperience of managing toxicitiesEarly recognition and prompt management of immune-mediated toxicityAccess to 2nd line immunosuppressive drugs like infliximab
Summary
Slide16Additional slides
Slide17Hyper / Hypothyroidism
ESMO
Clinical Practice Guidelines for
management of toxicities from immunotherapy.Ann Oncol. 2017;28(suppl_4):iv119-iv142. doi:10.1093/annonc/mdx225
Slide18H
ypophysitis
ESMO
Clinical Practice Guidelines for management of toxicities from immunotherapy.Ann Oncol. 2017;28(suppl_4):iv119-iv142. doi:10.1093/annonc/mdx225
Slide19Immune-mediated hepatitis
ESMO
Clinical Practice Guidelines for
management of toxicities from immunotherapy.Ann Oncol. 2017;28(suppl_4):iv119-iv142. doi:10.1093/annonc/mdx225
Slide20Immune mediated nephritis
ESMO
Clinical Practice Guidelines for
management of toxicities from immunotherapy.Ann Oncol. 2017;28(suppl_4):iv119-iv142. doi:10.1093/annonc/mdx225
Slide21Peripheral
Neuro
-toxicity (1)
ESMO Clinical Practice Guidelines for management of toxicities from immunotherapy.Ann Oncol. 2017;28(suppl_4):iv119-iv142. doi:10.1093/annonc/mdx225
Slide22Peripheral
Neuro
-toxicity (2)
ESMO Clinical Practice Guidelines for management of toxicities from immunotherapy.Ann Oncol. 2017;28(suppl_4):iv119-iv142. doi:10.1093/annonc/mdx225
Slide23Central
Neuro
-toxicity
ESMO Clinical Practice Guidelines for management of toxicities from immunotherapy.Ann Oncol. 2017;28(suppl_4):iv119-iv142. doi:10.1093/annonc/mdx225
Slide24S
kin toxicity
ESMO
Clinical Practice Guidelines for management of toxicities from immunotherapy.Ann Oncol. 2017;28(suppl_4):iv119-iv142. doi:10.1093/annonc/mdx225
Slide25Arthralgia
ESMO
Clinical Practice Guidelines for
management of toxicities from immunotherapy.Ann Oncol. 2017;28(suppl_4):iv119-iv142. doi:10.1093/annonc/mdx225