Nodular Regenerative Hyperplasia Induced by Trastuzumab Emtansine: Role of Emtansine?

Lepelley, Marion; Allouchery, Marion; Long, Jérôme; Boucherle, Dorothée; Ranchoup, Yves; Marc’hadour, F. Le; Villier, Céline; Stürm, Nathalie

doi:10.5604/01.3001.0012.7207

Cited by 10 publications

(11 citation statements)

References 25 publications

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“…Transaminases elevation was present in every case of NRH, including ours. [7][8][9] The extent of the augmentation was variable but stayed below three times the normal upper limit. 7,8 Including our case, thrombocytopenia was present in half of the reported cases with the lowest reported value being 99 Â 10 9 /L.…”

Section: Discussionmentioning

confidence: 99%

“…16 The published cases of NRH caused by T-DM1 have reported clinical or radiographic signs of portal hypertension with either ascites or esophageal varices as overt signs of portal hypertension, which occurred after a median of 15 months after the initiation of T-DM1 (interval 2 to 26 months). [6][7][8][9] Only one patient (13%) presented an early presentation of NRH two months after T-DM1 therapy, while all other cases occurred after a minimum of 12 months. Therefore, NRH may be suspected after one year of T-DM1 treatment in patients with signs of portal hypertension without cirrhosis.…”

Section: Discussionmentioning

confidence: 99%

“…Cases of T-DM1-induced NRH in the literature. [6][7][8][9] Patient and age at presentation of NRH Manifestation of NRH During her treatment with T-DM1, the patient had progressive stellate angiomas. Multiple abdominal CT-scans were done during her treatment period, and they showed a stable hypodensity lesion in segment IV-A with a small element of steatosis without portal thrombosis nor hepatic metastasis.…”

Section: Case Reportmentioning

confidence: 99%

“…There was only one reported case where trastuzumab was reintroduced following the diagnosis of NRH and was continued for one month until metastatic progression. 9 In this case report, we present one case where trastuzumab was reintroduced without any complications for a long extent following T-DM1-associated NRH.…”

Section: Introductionmentioning

confidence: 95%

“…[3][4][5] There are seven T-DM1-induced nodular regenerative hyperplasia (NRH) cases described in the literature (Table 1). [6][7][8][9] NRH usually presents itself with a mild elevation of transaminases occurring over several months, followed by clinical signs of portal hypertension such as ascites, hypersplenism and variceal bleeding. 10 Mildly elevated transaminases usually do not require an interruption of therapy, but unaddressed NRH can lead to severe hepatic damage with one case of death from liver failure reported in the literature.…”

Section: Introductionmentioning

confidence: 99%

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Safety of trastuzumab after trastuzumab emtansine-induced nodular regenerative hyperplasia: A case report

Hassan

Correal

Vézina

et al. 2020

J Oncol Pharm Pract

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Introduction Trastuzumab emtansine is an antibody-drug conjugate targeting the human epidermal growth factor receptor 2 use in recurrent metastatic breast cancer. Cases of trastuzumab emtansine-induced nodular regenerative hyperplasia are often reported as overt noncirrhotic portal hypertension with ascites and variceal bleeding. Case report We report the case of a 61-year-old woman who present multiple stellate angiomas with gradual increased liver transaminases and reduced platelet count during a 27-months course on trastuzumab emtansine therapy for recurrent metastatic breast cancer. After the nodular regenerative hyperplasia was histologically confirmed, the trastuzumab emtansine was stopped. After two months, trastuzumab was restarted together with exemestane. During trastuzumab therapy, the patient had a normalization of liver transaminases, platelet count and a gradual improvement of her stellate angiomas. Trastuzumab was continued for 15 months without any reoccurrence of nodular regenerative hyperplasia. Management and outcome Nodular regenerative hyperplasia should be suspected after one year of trastuzumab emtansine treatment in patients with signs of portal hypertension without cirrhosis. Definitive cessation of trastuzumab emtansine is required after a diagnosis of nodular regenerative hyperplasia and complete resolution of symptoms generally takes several months. Discussion Based on fundamental studies, nodular regenerative hyperplasia is probably caused by the emtansine (DM1) part of the trastuzumab emtansine. It is still unclear if trastuzumab therapy can be reintroduced after nodular regenerative hyperplasia induced by trastuzumab emtansine, depriving the patient of a HER2-targeted therapy. Only one case reported having given trastuzumab in this situation over one month. In our case, trastuzumab was reintroduced without any complications for a long extent following TDM1-associated nodular regenerative hyperplasia.

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