SLIDE 1 Case Presentation:
Immune related adverse events
Medical Oncologist
SLIDE 2 Some principles…
- irAEs are generally manageable and low
grade
- Can also cause severe morbidity & mortality
- Vigilance and immediate aggressive
management can be life saving
SLIDE 3 The Good, The Bad & The Ugly
Aka: Immunotherapy Vitiligo Colitis Aka: irAEs Pneumonitis
SLIDE 4
Case 1
Vitiligo
SLIDE 5 Case 1
- Diagnosed in 2009
- 32 yr Female
- Excision - lesion left upper back
- Breslow 0.7mm, Clark level 3, no ulceration
- Margins extended
- Stage 1A (T1N0M0)
- Observed
SLIDE 6 PD
- 2013 – back pain and leg pain
- Restaged – CT scan : Lung mets, pre –sacral
soft tissue pelvic mass
- Elsewhere: January 2013 – received DTIC 3m –
No response Ipilimumab (EAP) April 2013 x 4 cycles
CR – Still in remission…
SLIDE 7
Lung Metastases
SLIDE 8
PET image
SLIDE 9
Complete response
SLIDE 10
Vitiligo
SLIDE 11
SLIDE 12
SLIDE 13 OS benefit in melanoma patients with Vitiligo
Teulings H, Limpens J, Jansen S et al. J Clin Oncol 2015; 33:773–81
SLIDE 15
Case 2
March 2014 62yr Female Left Axilla: 50x41mm tumour Biopsy: Metastatic Melanoma BRAF Negative CT: Left Axillary node, Left subphrenic mass, Left & right renal mass Comorbidities: HT/DM/Dyslipidaemia
SLIDE 16
Treatment
May 2014 – Dacarbazine Jul 2014 - 4 cycles PD – Clinically in size of mass Sep 2014 – Ipilimumab (EAP) 4 Cycles (last dose 31/10/14) Very good PR
SLIDE 17
Response
SLIDE 18
SLIDE 19
SLIDE 20
SLIDE 21 irAE
- 4 days of loose stools - >4/day
- Associated abdominal pain
- 6 Jan 2015 - Admitted for colitis
(+/- 9 weeks after last dose)
SLIDE 22 Management
- Rehydration
- High dose Steroids
- Responded for short periods – relapsed
- Colonoscopy done + biopsy: 19 Jan 2015
Histology: ulceration, loss of mucosal tissue with inflamed granulation tissue with mixed inflammatory infiltrate (comprised
- f lymphocytes, plasma cells and scattered eosinophil leucocytes
SLIDE 23
Colonoscopy
SLIDE 24 Immunosuppressive Therapy
- 4 weeks later
- Infliximab initiated (450mg) 9 Feb 2015
- Responded in 72 hours
SLIDE 25
- Early initiation of diarrhea treatment
accoerding to guidelines has been shown to reduce bowel perforation and colectomy rates and serious GI irAEs by up to 50%
SLIDE 26 Follow up
- Last CT - Ongoing partial response
- Axillary lesion – not seen
- Renal upper pole mass – small residual nodule
11x6mm
SLIDE 28 Case 3
- Initial Dx – 2014 (Adeno)
- Rx – RUL/RML Lobectomy (Stage 1b - T2aN0)
- Adjuvant Carbo/Pac x4
- PD – July 2016 – lung nodules / axillary nodes
- Trial – BMS: CA209227 - Combo Ipi/Nivo
SLIDE 29 General Principles
- GI IrAEs - > CTLA-4 inhibitors
- Pneumonitis > PD-1 inhibitors
- > Grade 3 or 4 adverse events with CTLA-4
blockers
- Combination = more frequent & more toxicity
SLIDE 30
Skin Rash – Aug 2016
Occurred after C1
SLIDE 32 Treatment
- Long hospital stay – high dose corticosteroids
- PR after initial dose
- Continued on Nivo alone
- Restarted treatment Nov 2016 (3m later)
SLIDE 33
Response
Aug 2016 Nov 2016
SLIDE 34
Response
Aug 2016 Nov 2016
SLIDE 35 June 2018
Months after onset: 22m
Non specific sx Unwell No SOB No resp distress Decreased sats
SLIDE 36 Kinetics of Onset and Resolution of PD-1/PD-L1 Treatment- Related AEs
Weber JS, et al. J Clin Oncol. 2017;35:785-792.
*Any grade.
Median Time (Wks) Approximate Proportion
8 7 6 5 4 3 2 1 2 3 4 Endocrine* Hepatic* Pulmonary* Renal* 1
SLIDE 37 Radiology
CR - Mar 2018 Pneumonitis - June 2018
SLIDE 38
Pneumonitis
SLIDE 39
Normal lung – Mar 2018 Pneumonitis – June 2018
SLIDE 40 Treatment
- Long hospital stay
- Hi-flo O2
- High dose corticosteroids
- Eventually deceased – Oct 2018 (3m after onset of
pneumonitis)
SLIDE 41 Conclusion
Proactive Monitoring Early recognition and reporting Prompt Appropriate Management Vigilant follow up
SLIDE 42
Always remember…
