Partial Splenic Embolization for Lenvatinib Therapy-associated Thrombocytopenia Among Patients With Hepatocellular Carcinoma

Abstract

Background: Lenvatinib, a newly developed oral multi-tyrosine kinase inhibitor, has amazing potential in the multidisciplinary treatment of advanced or metastatic hepatocellular carcinoma. Thrombocytopenia is a serious adverse event that causes drug dose reduction or withdrawal. Partial splenic embolization is currently being used as a non-surgical treatment for thrombocytopenia caused by various pharmacotherapies. Case Report: Partial splenic embolization was performed for three patients with hepatocellular carcinoma receiving lenvatinib therapy with/without transarterial chemoembolization. Partial splenic embolization was advantageous for various situations, including the induction of lenvatinib for patients with thrombocytopenia, application of lenvatinib after multiple transarterial chemoembolization using cisplatin and radiotherapy, and re-administration of lenvatinib after lenvatinib therapy-induced thrombocytopenia. In all cases, lenvatinib therapy was completed without need for cessation due to thrombocytopenia. Conclusion: We strongly recommend the new concept of combining partial splenic embolization and lenvatinib therapy for hepatocellular carcinoma.Multidisciplinary treatment, including molecular targeted therapy, is recommended for advanced or metastatic hepatocellular carcinoma (HCC) (1-4). Lenvatinib is a newly developed oral multi-tyrosine kinase inhibitor that can provide greater tumor regression and tumor necrosis compared to sorafenib (5-7). Since March 2018, lenvatinib has become available for use in the treatment of HCC in Japan and its use has been spreading globally (8-10). Lenvatinib is generally indicated for patients with good liver functional reserve, i.e. those with Child-Pugh score of 5 or 6 points (5, 6). Nonetheless, even for patients with advanced HCC who have chronic liver disease, lenvatinib was reported to have an acceptable safety profile (4, 9, 10). The phase III REFLECT trial comparing lenvatinib and sorafenib demonstrated different adverse events profiles. Accordingly, more than 5% patients in the lenvatinib group developed several grade three or more adverse events, including hypertension (23%), reduced appetite (5%), reduced weight (8%), protein urine (6%), reduced platelet count (5%), elevated aspartate aminotransferase (5%), and increased blood bilirubin (7%). ( 6) The lenvatinib group had fewer instances of palmar-plantar erythrodysesthesia (27%) than the sorafenib group (52%). Moreover, a systematic review and meta-analysis for lenvatinib cancer therapy demonstrated that thrombocytopenia (25.4%), hypertension (17.7%), and peripheral edema (15.5%) were the most frequent adverse events (grade ≥3) (11).Partial splenic embolization (PSE) has been developed as a non-surgical treatment for alterations in blood cell count, especially platelet count (12-14). However, hypersplenism due to liver cirrhosis has remained the main reason for application of PSE. Recently, indications for PSE have expanded to include coexisting hypersplenism in chemotherapy patients, pretreatment for...

Comparison of therapeutic outcomes of sorafenib and lenvatinib as primary treatments for hepatocellular carcinoma with a focus on molecular‐targeted agent sequential therapy: A propensity score‐matched analysis

“…Considering the selection of first‐line MTAs for u‐HCC, LEN might be preferable to SOR when tumor shrinkage is needed for controlling intrahepatic tumors, which are at a high risk of rupture or macrovascular invasion 26 . Moreover, LEN is expected to show a high possibility of downstaging u‐HCC with a high tumor burden, resulting in a switch to locoregional therapies such as conversion hepatectomy 27–29 . However, more studies are needed for investigating the therapeutic efficacy of conversion therapy using LEN.…”

“…26 Moreover, LEN is expected to show a high possibility of downstaging u-HCC with a high tumor burden, resulting in a switch to locoregional therapies such as conversion hepatectomy. [27][28][29] However, more studies are needed for investigating the therapeutic efficacy of conversion therapy using LEN.…”

Severe Thrombocytopenia Associated With Pembrolizumab in Patients With Non-small Cell Lung Cancer (NSCLC): A Case Report and Literature Review

“…When thrombocytopenia persists for several weeks, steroid or intravenous IgG may be necessary. The management by platelet transfusion is a main issue in patients with severe thrombocytopenia secondary to cytotoxic chemotherapy, whereas, systemic steroid and immunoglobulin administration is identified as a reasonable choice in those due to immunotherapy (9)(10)(11).…”

Multiple Splenic Artery Aneurysms: A Case Report and Review of the Literature

“…The prognosis of such patients may be poor when open surgery is abruptly performed. Partial embolization of splenic vessels is reportedly used to treat hypersplenism of thrombocytopenia, and partial splenic embolization is an effective method for improving the platelet count (2,(42)(43)(44)(45). Embolization is primarily performed in the inflow and outflow tracts of aneurysms, and it is not necessary to completely embolize the aneurysm sac.…”