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Various toxicities: 2 case reports In a study a 28-year-old woman and a 66-year-old man developed liver-dysfunction, erythema nodosum, high fever, interstitial pneumonia or rebound of melanoma due to ipilimumab, dabrafenib and trametinib (1 patient) or dabrafenib and trametinib (1 patient) [routes not stated; not all outcomes stated]. Patient 1: The 28-year-old woman was diagnosed with BRAFV600E mutated melanoma on the lateral chest. She presented with multiple metastases, and therefore started receiving ipilimumab 3 mg/Kg every 3 weeks. On day 49 of ipilimumab (following third-administration) she developed grade 3 liver-dysfunction. Ipilimumab was discontinued. However, the melanoma progressed (detected by increase in BRAFv600E level increase and a CT-scan finding). Of note, elevated LDH (due to ipilimumab) contributed to the onset of liver-dysfunction. Following ipilimumab discontinuation, the LDH normalised as the liver function improved on day 217. Melanoma therapy was started with dabrafenib 300mg daily and trametinib 2 mg/day on day 252 of ipilimumab. However, on day 49 she developed grade 2 high fever, grade 3 liver dysfunction and grade 2 erythema nodosum. Therefore, dabrafenib and trametinib was tapered and withdrawn on day 49. A CT scan scan on day 91 revealed enlargement of the tumour, along with a rebound in BRAFV600E ctDNA levels. Pembrolizumab was started for the rebound in melanoma. The melanoma stabilised (noted on day 105 and 149 of pembrolizumab). Patient 2: The 66-year-old man was diagnosed with BRAFV600E-mutated melanoma on his chest. He presented with multiple metastases, and started receiving dabrafenib 300 mg/day and trametinib 2mg daily. On day 189 of treatment initiation, dabrafenib and trametinib were withdrawn due to drug-induced grade 2 interstitial pneumonia (which started on day 70 and progressed on day 147). Additionally, LDH level increased. On day 245 his BRAFV600E ctDNA levels increased. Due to tumour relapse, he again started receiving dabrafenib 300 mg/day and trametinib at 1.5 mg daily from day 273 (during which interstitial pneumonia improved to grade 1 and LDH level normalised). On day 277 ctDNA became undetectable. Additionally, LDH remained in normal range. Author comment: "However, it can be difficult to determine whether LDH elevation is caused by therapyrelated [adverse events]." "[A] CT scan. . . revealed enlargement of the tumour, along with a rebound in BRAFV600E ctDNA levels." Ashida A, et al. Circulating tumour DNA reflects tumour burden independently of adverse events caused by systemic therapies for melanoma. Acta DermatoVenereologica 99: 1184-1185, No. 12, 1 Nov 2019. Available from: URL: http:// 803439857 doi.org/10.2340/00015555-3279 - Japan

0114-9954/19/1783-0001/$14.95 Adis © 2019 Springer Nature Switzerland AG. All rights reserved

Reactions 14 Dec 2019 No. 1783