Metastatic uveal melanoma showing durable response to ipilimumab and nivolumab combination therapy after experiencing progression on anti-PD-1 therapy alone
- 3 years ago
J Immunother Cancer. 2018 Feb 12;6(1):13. doi: 10.1186/s40425-018-0322-1.
Our patient is a 72-year-old man with a history of Sweet’s syndrome, hypertension, hyperlipidemia, basal cell carcinoma and psoriasis. He presented with acute painless vision loss described as a rapidly progressing “curtain” over his left eye in December 2014. There was no history of trauma or other antecedent events to have caused retinal detachment. Emergent examination of the eye revealed an approximately 2-cm mass lesion and ultrasound confirmed a 1.2-cm dome-shaped lesion involving the ciliary body. Laboratory evaluations including complete blood counts, chemistries, and hepatic function tests were normal at that time. Brain MRI confirmed a left globe lesion tracking along the retina, but no evidence of other intracranial lesions and positron emission tomography/computed tomography (PET/CT) did not show any evidence of metastatic disease.
He underwent a curative-intent enucleation two months later with pathology confirming left ciliary body melanoma. Primary pathology showed ciliochoroidal malignant melanoma with no extra-scleral extension. The tumor had zones of necrosis and numerous areas with epithelioid and spindle melanoma cells. There were areas of necrosis within the tumor but no evidence of extra-scleral extension.
Unfortunately, his initial surveillance PET/CT scan six months after enucleation revealed diffuse liver metastases. Laboratory evaluations remained normal including his lactate dehydrogenase (LDH). MRI of the liver confirmed numerous enhancing lesions, with the largest measuring 3.8 cm in the anterior right lobe [Fig. 1a and b].
Liver biopsy confirmed this to be metastatic melanoma consistent with an ocular primary. Molecular profiling did not reveal actionable mutations in c-kit, Braf, or Ras, but did show a mutation in GNA11 (codon 626 A to T). He was treated with nivolumab 3 mg/kg every two weeks and completed four cycles prior to obtaining a restaging MRI. Unfortunately, this showed the progression of disease in the liver with the largest right lobe lesion now measuring 5.5 cm [Fig. 1c]. The patient also reported increasing vague abdominal fullness, intermittent nausea and his LDH was noted to be rising (333 U/L, upper limit of normal 220).
Later that month, following FDA approval, the patient was started on nivolumab 1 mg/kg with ipilimumab 3 mg/kg every three weeks. A restaging abdominal CT scan after two cycles of treatment showed overall stable disease in size and, his increasing abdominal symptoms were felt to be related to the liver disease as he continued to experience rise in his LDH (now 514); Following completion of therapy cycle four, his abdominal symptoms started to improve, and his LDH started to decrease falling from a peak of 993 to 420 U/L over three weeks [Fig. 2]. A restaging MRI, three weeks after cycle number four showed mixed response with some signal changes consistent with treatment effect but other lesions were conc
Our patient is a 72-year-old man with a history of Sweet’s syndrome, hypertension, hyperlipidemia, basal cell carcinoma and psoriasis. He presented with acute painless vision loss described as a rapidly progressing “curtain” over his left eye in December 2014. There was no history of trauma or other antecedent events to have caused retinal detachment. Emergent examination of the eye revealed an approximately 2-cm mass lesion and ultrasound confirmed a 1.2-cm dome-shaped lesion involving the ciliary body. Laboratory evaluations including complete blood counts, chemistries, and hepatic function tests were normal at that time. Brain MRI confirmed a left globe lesion tracking along the retina, but no evidence of other intracranial lesions and positron emission tomography/computed tomography (PET/CT) did not show any evidence of metastatic disease.
He underwent a curative-intent enucleation two months later with pathology confirming left ciliary body melanoma. Primary pathology showed ciliochoroidal malignant melanoma with no extra-scleral extension. The tumor had zones of necrosis and numerous areas with epithelioid and spindle melanoma cells. There were areas of necrosis within the tumor but no evidence of extra-scleral extension.
Unfortunately, his initial surveillance PET/CT scan six months after enucleation revealed diffuse liver metastases. Laboratory evaluations remained normal including his lactate dehydrogenase (LDH). MRI of the liver confirmed numerous enhancing lesions, with the largest measuring 3.8 cm in the anterior right lobe [Fig. 1a and b].
Liver biopsy confirmed this to be metastatic melanoma consistent with an ocular primary. Molecular profiling did not reveal actionable mutations in c-kit, Braf, or Ras, but did show a mutation in GNA11 (codon 626 A to T). He was treated with nivolumab 3 mg/kg every two weeks and completed four cycles prior to obtaining a restaging MRI. Unfortunately, this showed the progression of disease in the liver with the largest right lobe lesion now measuring 5.5 cm [Fig. 1c]. The patient also reported increasing vague abdominal fullness, intermittent nausea and his LDH was noted to be rising (333 U/L, upper limit of normal 220).
Later that month, following FDA approval, the patient was started on nivolumab 1 mg/kg with ipilimumab 3 mg/kg every three weeks. A restaging abdominal CT scan after two cycles of treatment showed overall stable disease in size and, his increasing abdominal symptoms were felt to be related to the liver disease as he continued to experience rise in his LDH (now 514); Following completion of therapy cycle four, his abdominal symptoms started to improve, and his LDH started to decrease falling from a peak of 993 to 420 U/L over three weeks [Fig. 2]. A restaging MRI, three weeks after cycle number four showed mixed response with some signal changes consistent with treatment effect but other lesions were conc