Ipilimumab/nivolumab

Abstract

A 47-year-old man developed demyelinating diseases during treatment with ipilimumab and nivolumab for malignant melanoma. The man, who had malignant melanoma, presented with an ulcerated melanoma of the occipital scalp. The molecular analysis showed a BRAF V6000E mutation, NRAS wild-type and KIT wild-type. He underwent left-sided neck dissection (level 2-4) without any signs of tumour spread. As per the American Joint Committee on Cancer (AJCC), the staging at diagnosis was IIc and switched to IIIc after sentinel lymph node biopsy. Hence, he started receiving combinatorial treatment arm with nivolumab 240mg, every 2 weeks and ipilimumab 1 mg/kg, every 6 weeks [routes not stated]. After 5 weeks of treatment, he developed evidence of cerebellar disease with pathologic heel-to-shin exam, gait ataxia and dysmetria. Over time, his symptoms worsened.Hence, the man's treatment was discontinued after 3 cycles of nivolumab and 2 cycles of ipilimumab. The brain MRI showed several spot-shaped periventricular, parenchymal and leptomeningeal contrast enhancements, indicative of parenchymal and predominantly leptomeningeal metastasis. The spine MRI was consistent with leptomeningeal metastasis with nodular enhancement tracking, along with the thoracic and cervical segments and conus terminalis. The CSF examination revealed mild elevation of protein level and a moderate elevation of lymphomononuclear pleocytosis. However, the tumour cells were absent. No melanoma cells were observed, and no signs of lymphoma were observed in a clonality analysis for T and B-cell receptors. The neuropathologic examination revealed white matter tissue with reactive gliosis and abruptly demarcated demyelinated areas, positive staining for myelin protein CNPase and MBP, dense macrophagocytic infiltrates and perivascular accentuated lymphocytic CD45+ infiltrates including CD3+ and CD20+ cells of low to moderate density. The tissue showed negative results for lymphoblastoid B or T-cells, clonality analysis and melanosomal antigens (Melan A and HMB45). Also, no IDH-1 R132H mutationspecific stainability, p53 accumulation or alpha-thalassemia/mental retardation syndrome X-linked (ATRX) loss were observed. His findings were considered pseudomeningeosis. Based on findings, a diagnosis of ipilimumab and nivolumab-induced demyelinating diseases was made. Hence, he received corticosteroid treatment, which resulted in prompt clinical improvement. Six weeks later, the CSF and MRI examination showed a near-complete remission. He did not receive any other tumour directed treatment. At the latest follow-up (on May 2020), no signs of tumour progression were observed. He remained progression-free for 22 months.