Hepatic cavernous hemangioma developed in non-small cell lung cancer patients after receiving Camrelizumab treatment: two case reports

Abstract

PurposeTo report two cases of hepatic cavernous hemangioma, a rare complication, in patients with locally advanced and advanced non-squamous non-small cell lung cancer (NSCLC) treated with PD-1 inhibitors. Additionally, to share clinical experiences related to the management of this condition.MethodsTwo patients with locally advanced and advanced non-squamous non-small cell lung cancer (NSCLC) were enrolled in our hospital. Following the NCCN guidelines and expert consensus, both patients received standard treatment with Camrelizumab (PD-1 inhibitor). Subsequent abdominal CT scans revealed hepatic focal lesions that did not exhibit typical characteristics of metastatic tumors. Therefore, further systematic investigation was conducted to study the hepatic focal lesions.Results(1) Ultrasound-guided percutaneous biopsy confirmed the diagnosis of hepatic cavernous hemangioma. A multidisciplinary consultation concluded that it was an adverse drug reaction to Camrelizumab. (2) Ten-gene testing for both patients did not reveal any driver gene mutations associated with lung cancer. Apart from the occurrence of hepatic cavernous hemangioma, there were no signs of disease progression or worsening. (3) Both patients had resolution of hepatic cavernous hemangioma after switching to alternative PD-1 inhibitors or discontinuing PD-1 inhibitor treatment. One patient experienced hemorrhage related to the hepatic hemangioma, which was managed with hemostasis and symptomatic treatment, resulting in improvement. (4) Clinical outcomes: The first patient achieved a progression-free survival (PFS) of 33 months in first-line treatment and had not reached the PFS endpoint in second-line treatment, with an overall survival exceeding 56 months. The second patient had not reached the PFS endpoint in first-line treatment, with an overall survival exceeding 31 months.ConclusionHepatic cavernous hemangioma is a rare and serious adverse reaction associated with PD-1 inhibitors. Camrelizumab may interact with the PD-1 molecule in a different manner compared to other PD-1 inhibitors, affecting the regulation of the VEGFR/ULBP2 signaling pathway. In future studies, next-generation sequencing may provide detailed molecular pathology information, which could help explain individual differences and provide a basis for the prevention or intervention of hepatic cavernous hemangioma.

Case report: A rare immune-related adverse effect: hepatic cavernous hemangioma induced by camrelizumab

“…The first and second cases reported RCCEP in the skin and anus, among other locations, which were not mentioned in the third case. Furthermore, the resolution of hepatic cavernous hemangiomas in the first and third cases after discontinuing camrelizumab underscores the potential reversibility of these effects, echoing findings from previous research (13,18).…”

“…Prior to this study (13), a solitary article identified just two instances of hepatic hemangioma related to camrelizumab In this study, we present the first account of six patients who developed hepatic hemangiomas after undergoing 5, 16, 12, 14, and 4 cycles of camrelizumab therapy, respectively. In Yonglong Yu's study (13), the number of therapy cycles reported shows similarities to those in our investigation.…”

“…Moreover, literature lacks reports of RCCEP or hemangioma induction by bevacizumab (14), trastuzumab (15,16), nimotuzumab (17), and chemotherapy, further complicating the assessment of these agents' roles in such pathologies. In the study conducted by Yonglong (13), it was observed that the hepatic cavernous hemangioma resolved upon the cessation of camrelizumab treatment or when patients were switched to alternative PD-1 inhibitors. This outcome suggests a direct correlation between the medication and its adverse effects.…”

“…Camrelizumab's unique, low-affinity interaction with VEGFR2's extracellular domain, functioning as an agonist, is pinpointed as a potential mechanism for capillary hemangioma induction (13,19). This interaction stimulates vascular endothelial cells, fostering hemangioma formation (13).…”

“…Previous study indicated that the RCCEP occurred mainly on the skin surface, oral cavity, and nasal cavity. Although there are case reported (13) on hepatic hemangioma, its documentation in the literature remains sparse. This case series presented 6 cases of patients who experienced hepatic hemangiomas after multiple cycles of therapy including camrelizumab.…”