Immunotherapy and Cancer - PowerPoint Presentation

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Immunotherapy and Cancer

New treatments and new challengesLaura Cove-SmithMedical Oncology ConsultantThe Christie NHS Foundation TrustManchester University NHS Foundation Trust

Session plan

Introduction to immunotherapyKey changes in palliative treatment for advanced cancers (particularly lung/melanoma)Why recognising toxicity is importantKey toxicities

Case studies

Do I really need to know about it ?

Immunotherapy is the future of cancer treatment…..or so we think!Immunotherapy is becoming standard of care - superseding chemotherapy (lung, melanoma, renal, bladder)Lung 5 year survival has been 5% for > 20 yearsNow 20-25% 5 year survival being seen with immunotherapy

MelanomaPreviously 20% at 5yrs but now 50% live for 5

yrs

!

Thought to be much more tolerable/safer than chemotherapy

But as they are used more widely we realise that may not beDifferent toxicity – autoimmune problemsUnderestimated in trials as early trials only measured standard chemotherapy toxicity like neutropenia, nausea, vomiting Oncologist are having to rapidly learn to deal with new toxicitiesNot much experience of managing it, little consensus, unchartered waters…

Do I really need to know about it ?

How are they given?

30min IV infusionEvery 2-3 weeksNow looking at less often 4-6 weeklyContinuous for 2 years (at the moment) due to NICE approval through Cancer Drugs FundPS 0-1 (may patients don’t fit criteria)

Slower to work Can get pseudoprogression

/tumour flare

How do they work?

Anti-cancer immune defences in the body – T lymphocytes Cells express proteins on their surface – T cells interact with the proteins and recognise if cells are damaged/infected/cancerous and initiate a cascade of immune events that leads to cell death

Cancer evade these mechanisms by exploiting the natural control mechanisms that protect the body from autoimmunity

What toxicities do we see?

Pneumonitis

Colitis

Thyroiditis

Hepatitis

Skin toxicity

(including eyes and mms)

Nephritis

Neuropathies

Hypophysitis

Myocarditis

Most patient tolerate well and get very little

toxicity

If toxicity occurs it can be difficult to reverse but immediate treatment is high dose steroids

When does toxicity occur?

pneumonitis

thyroidtitis

Toxicity can occur at any time

even months after

the treatment is stopped

Grading system for immunotherapy side effects

Grade 1 (mild) – interrupt treatment/continue with close monitoring and may not need treat with steroidsGrade 2 (moderate) – PO steroids (1mg/kg pred)/interrupt treatmentGrade 3/4 (hospitalised/life threatening) –

IV methyl pred (2mg/kg) + PPI +PJP prophylaxis In no improvement in 3 days of IV methyl pred needs escalation – infliximab for colitis/pneumonitis/skin (not for liver tox – MMF)

We rarely retreat if G3/4 toxicity

Interactive real life case: no. 1

55 year old man with stage 4 indolent lymphomaPrevious antibody therapies and chemotherapyCycle 1 of palliative therapy with nivolumabDay 10 presented with mild conjunctivitis

What would you do?

What would you say to the patient?

What did we do?

Referred to opthalmology as OP given prednisolone eye dropsSpecialist nurse asked to contact patient in 48hrs

What did we do?

Referred to opthalmology as OP given prednisolone eye dropsSpecialist nurse asked to contact patient in 48hrs Day 12 – admitted with mucositis, widespread macular rash and worsening eye toxicity (exudate, visual loss, photophobia)

How would you manage this?

Skin Toxicity

Mild (Grade 1)

Localised macular/

Papular

eruption

Asymptomatic

Management Plan:

Daily monitoring

Anti-histamines

Localised rash

: Topical steroidal based cream (

Dermovate

cream

bd

)

Extensive or symptomatic rash

: prednisolone 0.5- 1mg/kg od x 3 days-max. 60mg/day

*+ PPI

Withold

treatment until ≤ grade 1

Management Plan:

Admit patient

Discontinue immunotherapy permanently

Contact local dermatology team for advice/biopsy

Commence IV hydration

High-dose IV corticosteroid therapy (

eg

, methylprednisolone 2 mg/kg

od +PPI

Regular

ob’s

and fluid balance

Anti-histamines-hydroxyzine 25mg

qds

max. 100mg daily

Topical emollient cream-

cetraben

*Consider prophylactic antibiotics

Management Plan:

Regular monitoring

Consider anti-histamines

Continue immunotherapy

Moderate

(Grade 2)

Rash affecting ≤ 50% skin surface

Itchy

Affecting ADL’s/sleep

Severe or Life-Threatening

(Grade 3 + 4)

Is defined as

any

of the following:

>50% skin surface

generalised

exfoliative

ulcerative

bullous dermatitis

*

ANTIBIOTIC PROPHYLAXIS:

Patients on steroid doses >Prednisolone 50mg/OD should be started on

antiotic

prophylaxis

Septrin960 mg/BD/ 3 times a week

Fluconazole 50 mg/OD

Aciclovir

200mg/QDS

UKONS guidelines – available on internet

https://www.nwcscnsenate.nhs.uk/files/9815/2759/2181/UKONS_AO_management_guidelines_-_Rev._March_2020.pdf

Development of TEN

Started on 1g methylprednisolone IVStarted on acyclovir, co-trimoxazole and fluconazole & Tazocin Eyes, mouth and rash continued to worsenHad regular

opthamology and dermatology inputTopical care advised and implemented by MAU nursesBegan to blister then desquamate

Skin biopsy at Salford

Transferred to DermatologySkin biopsy was typical of toxic epidermal necrolysis - TEN (full thickness epidermal/epithelial necrosis)Prophylactic antimicrobials stopped due to concern they were contributing to TEN

Respiratory Failure

6 weeks after initial presentation – he became acutely hypoxicWhat could be going on?

Respiratory Failure

6 weeks after initial presentation – he became acutely hypoxicWhat could be going on?Bronchscopy showed exudative damage of the mucus membranes in keeping with TEN of the airwaysCT more likely infection than pneumonitis?Grew aspergillus – treated with antifungalsDied 8 weeks after presentation

This is VERY RARE - most

patient tolerate well and get very little

toxicity

If toxicity occurs it can be difficult to reverse but immediate treatment is high dose steroids

Late effects?

Long lasting life changing acute eventsLate effects – unknown as yet

Where to get help?

UKONS guidelines available through google

!

https://www.ukons.org/resources/

Christie hotline

Christie Portal

Summary

Immunotherapy is changing practice and outcomes in many cancersGiven continuouslyMay take time to work but in selected patient we are seeing long term responseGenerally tolerated well but toxicity different and can be severeDon’t dismiss subtle new symptoms