Case Presentation: Immune related adverse events Dr. Ronwyn van - PowerPoint PPT Presentation

Case Presentation: Immune related adverse events Dr. Ronwyn van Eeden Medical Oncologist �

Some principles… • irAEs are generally manageable and low grade • Can also cause severe morbidity & mortality • Vigilance and immediate aggressive management can be life saving �

The Good, The Bad & The Ugly Aka: Immunotherapy Aka: irAEs Vitiligo Colitis Pneumonitis

Case 1 Vitiligo

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 �

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… �

Lung Metastases �

PET image �

Complete response �

Vitiligo �

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OS benefit in melanoma patients with Vitiligo Teulings H, Limpens J, Jansen S et al. J � Clin Oncol 2015; 33:773 – 81

Case 2 Colitis �

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 �

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 �

Response �

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irAE • 4 days of loose stools - >4/day • Associated abdominal pain • 6 Jan 2015 - Admitted for colitis (+/- 9 weeks after last dose) �

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 of lymphocytes, plasma cells and scattered eosinophil leucocytes �

Colonoscopy �

Immunosuppressive Therapy • 4 weeks later • Infliximab initiated (450mg) 9 Feb 2015 • Responded in 72 hours �

• 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% �

Follow up • Last CT - Ongoing partial response - Axillary lesion – not seen - Renal upper pole mass – small residual nodule 11x6mm - NIL else visible �

Case 3 Skin Rash & Pneumonitis �

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 �

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

Skin Rash – Aug 2016 Occurred after C1 �

Grade 3/4

Treatment • Long hospital stay – high dose corticosteroids • PR after initial dose • Continued on Nivo alone • Restarted treatment Nov 2016 (3m later) �

Response Nov 2016 Aug 2016 �

Response Nov 2016 Aug 2016 �

June 2018 No. of cycles: 37 Months after onset: 22m Non specific sx Unwell No SOB No resp distress Decreased sats �

Kinetics of Onset and Resolution of PD-1/PD-L1 Treatment- Related AEs 8 Endocrine* Approximate Proportion 7 Hepatic* Pulmonary* 6 of Patients (%) Renal* 5 *Any grade. 4 3 2 1 0 0 1 2 3 4 0 0 0 0 Median Time (Wks) Weber JS, et al. J Clin Oncol. 2017;35:785-792.

Radiology CR - Mar 2018 Pneumonitis - June 2018 �

Pneumonitis �

Normal lung – Mar 2018 Pneumonitis – June 2018 �

Treatment • Long hospital stay • Hi-flo O2 • High dose corticosteroids • Eventually deceased – Oct 2018 (3m after onset of pneumonitis) �

Conclusion Prompt Early Proactive Vigilant Appropriate recognition Monitoring follow up and reporting Management �

Always remember… �