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+Ms L, 46 yo
Medical history
Excision of 5 benign nevus (2011)
Family history
Father: Head and neck cancer
Social History
No alcohol or tobacco consumption Saleswoman
+ Toxicities of immunotherapy A case study Maria KFOURY Intern - - PowerPoint PPT Presentation
+ Toxicities of immunotherapy A case study Maria KFOURY Intern - - PowerPoint PPT Presentation
+ Toxicities of immunotherapy A case study Maria KFOURY Intern Medical Oncology + Ms L, 46 yo Medical history Excision of 5 benign nevus (2011) Family history Father: Head and neck cancer Social History No alcohol or
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+History of present illness
October 2015 December 2015 January 2016 Discovery of left axillary lymphadenopathy Biopsy CAP CT Head MRI : No lesions Melanoma metastasis, NRAS mutation BRAF WT
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CAP CT 04/01/16
Left axillary lymphadenopathy 10 x 5,2 cm No pulmonary, visceral or bone lesions
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+Multi-disciplinary Consultation Meeting 12/01/16
Aggressive melanoma stage III C No surgery :
Inflammatory skin Fast growing
PS 0 Systemic therapy Nivolumab + Ipilimumab
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+History of present illness
18 Jan 16 8 Feb 16 29 Fev 16 C1 C3 : no injection C2 Nivolumab 3 mg/ kg Ipilimumab 1 mg / kg well tolerated 15 Feb 16 Head CT Impaired vision Headache Vitiligo
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Head CT 29/02/16
Enlargement of the pituitary gland volume measured at 9 mm
(versus 6 mm) : evocative of hypophysitis
No brain or meningeal lesion
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+Assessment of hypophysitis
Hormonal tests
TSH, T3, T4 normal Cortisol normal FSH, LH normal
Endocrinologist’s advice :
Intravenous corticosteroids bolus of 1 mg / kg / day for 3 days Followed by oral corticosteroids 1 mg / kg / day : 100 mg/ day
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+History of present illness
Improvement of impaired vision and headaches C3 21/03/2016:
Nivolumab 3 mg/ kg + Ipilimumab 1 mg / kg
Discovery of a hepatitis :
Cytolysis: ALAT 100 N, ASAT 50 N Cholestasis : GGT 3 N, Bilirubine N TP 82%, Factor V normal Grade 4 Grade 3
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+Assessment of Hepatitis
No new medications Liver US 25/03/16 :
Homogenous hepatomegaly, no focal lesion, bile duct
dilatation, vesicular microlithiasis
Auto-immune assessment Bacterial analysis Viral serology: HIV
, HAV , HBV , HCV
PCR CMV
, EBV , HSV Negative
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+Assessment of Hepatitis
Immune-mediated hepatitis under corticosteroids No sign of hepatic failure Hepatologist’s advice :
Maintain of corticosteroids Monitoring of liver function tests and hemostasis No hepatotoxic medications If increase in cytolysis: liver biopsy
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+Immune-related adverse effects : Ipilimumab
Weber J et al, JCO 2012
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+History of present illness
21 Mar 16 M4 Assessment No blurry vision Improvement of hepatitis CAP CT Head MRI C3 Nivolumab Ipilimumab 11 Apr 16
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CAP CT 11/04/16
Decrease of left axillary lymphadenopathy by 54%
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Head MRI 11/04/16
Enlargement of the pituitary gland measured at 7 mm, no
bulging into the sellar diaphragm
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+History of present illness
21 Mar 16 11 Apr 16 17 May 16 Left axillary lymphadenectomy
1N+/7N of 4 cm
C3 Nivolumab Ipilimumab M4 Assessment Multi-disciplinary consultation meeting :
Cessation of immunotherapy (cytolysis grade 4). Continuation of corticosteroids
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+History of present illness
21 Mar 16 M7 assessment Clinical exam : normal Biological tests: normal CAP CT : no lesions Head MRI : Decrease of the
pituitary gland’s volume
18 Jul 16 17 May 16 C3 Nivolumab Ipilimumab Left axillary lymphadenectomy
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+History of present illness
21 Mar 16 External radiation therapy axillary area
50 Gy in 25 fractions
17 May 16 Sept – Nov 16 M11 assessment Clinical exam : normal Biological tests: normal CAP CT, Head MRI :stable
C3 Nivolumab Ipilimumab
Left axillary lymphadenectom y
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CAP CT 07/11/16
No suspicious lesion
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+Conclusion
Persistance of a complete response 9 month after the 3rd and last injection of Nivolumab and Ipilimumab for a stage III melanoma
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Restrospective study 2011-2013 298 patients with melanoma included Ipililumab 3 mg/ kg 103 patients (35%) required corticosteroid 29 (10%) required anti-TNFα therapy
Immune-Related Adverse Events, Need for Systemic Immunosuppression, and Effects on Survival and Time to Treatment Failure in Patients With Melanoma Treated With Ipilimumab at Memorial Sloan Kettering Cancer Center
Horvat T et al, JCO 2015
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