PRES Secondary to the LenvatinibPembrolizumab Combination in a Patient with Serous Endometrial Adenocarcinoma

Antoine Salambo Mabila-; Anne Landais; Donald Accrombessi; Arcel Woga Nitcheu; Rodrigue Domingo; Martial Zossou; Ezechiel Ntakirutimana; Philippe Ntalaja; Webert Lafrance; Annie Lannuzel

PRES Secondary to the LenvatinibPembrolizumab Combination in a Patient with Serous Endometrial Adenocarcinoma

by Antoine Salambo Mabila^1-3*, Anne Landais¹, Donald Accrombessi¹, Arcel Woga Nitcheu¹, Rodrigue Domingo¹, Martial Zossou¹, Ezechiel Ntakirutimana¹, Philippe Ntalaja², Webert Lafrance⁴, Annie Lannuzel¹

¹Neurology Department/ CHU Guadeloupe

²Department of Neurology, Neuropsycho-pathological Center, University of Kinshasa (DRC), Congo

³Medical School, Notre-Dame University of KASAYI/DRC, Congo

⁴Oncology Department / CHU Guadeloupe

*Corresponding author: Antoine Salambo Mabila, Neuropsychopathological Center (CNPP), University of Kinshasa/ DRC, Congo

Received Date: 04 September, 2023

Accepted Date: 08 September, 2023

Published Date: 11 September, 2023

Citation: Salambo Mabila AS, Landais A, Accrombessi D, Nitcheu AW, Domingo R, et al. (2023) Pres Secondary to the LenvatinibPembrolizumab Combination in a Patient with Serous Endometrial Adenocarcinoma. Int J Cerebrovasc Dis Stroke 6: 162. https://doi.org/10.29011/2688-8734.100162

Summary

The combination of Lenvatinib and Pembrolizumab has benefited from Early Access Authorization in France since March 2022 in the treatment of advanced or recurrent endometrialc ancer.

We present a case of PRES secondary to the combination of Lenvatinib and Pembrolizumab int he treatment of an invasive endometrial serous adenocarcinoma.

A 66-year-old woman with serous endometrial adenocarcinoma diagnosed two years earlier in the context of peritoneal carcinomatosis, with dissociated response after 6 courses of CARBOPLATIN TAXOL, was put on second-line treatment with LENVATINIB and PEMBROLIZUMAB. The patient presented, five days after the third course, headaches of rapidly increasing intensity. Cerebral imaging was performed revealing T2 hypersignals, bilateral, subcortical, posterior, asymmetrical, and predominant on the right without ADC restriction, in favor of a PRES, motivating the discontinuation of the two incriminated molecules. The evolution was marked by the regression of clinical and radiological signs. The patient subsequently underwent a Pet scan, which revealed progressive disease with uterine, peritoneal, hepatic, adrenal, lymph node and pulmonary lesions, indicating the use of third-line CAELYX.

Our case highlights the importance of considering this new therapeutic combination (Lenvatiniba nd Pembrolizumab) as likely to be associated with PRES. Rigorous neurological clinical monitoring and the use of brain imaging in the face of signs suggestive of PRES are necessaryi n patients benefiting from this treatment.

Keywords: PRES; Lenvatinib-Pembrolizumab combination; Endometrial adenocarcinoma

Introduction

Posterior reversible encephalopathy syndrome (PRES) is a neurological disorder of (sub) acute onset characterized by varied neurological symptoms [1]. PRES is associated with a wide range of clinical presentations, including headache, focal neurological deficits, seizures, visual disturbances, and encephalopathy. The severity and acuity of clinical symptoms vary, although they usually occur with a rapid onset [2]. On average, approximately 40% of all patients diagnosed with PRES require intensive care monitoring and treatment due to serious complications such as status epilepticus, cerebral ischemia, intracerebral hemorrhage, or intracranial hypertension [1].

Several risk factors associated with PRES have been identified. PRES is associated with a multitude of diverse clinical entities, the most common of which are eclampsia, hypertension, and immunosuppressive therapy. Activation/disruption of the immune system has recently been considered a critical initial step in the pathogenesis of PRES and plays a central role in disease development [3,4]. Because PRES is reversible and easily treated by controlling blood pressure and stopping the offending immunosuppressive agent or decreasing the dose, it should be recognized quickly [4]. Immunosuppressive or cytotoxic drugs, such as Cyclosporin A, Tacrolimus/FK-506, Methotrexate, Sirolimus, Lenvatinib are implicated in the occurrence of PRES [3]. Some of these drugs are used in the management of endometrial cancer. In September 2019, the combination of Pembrolizumab (200 mg intravenously [IV] every 3 weeks) and Lenvatinib (20 mg orally [po] daily) received accelerated approval from the FDA for the treatment of cancer of advanced endometrium that had progressed on prior systemic therapy [5,6].

In France, the Early Access Authorization was granted on March 17, 2022 to the specialty LENVIMA (Lenvatinib) in the indication “in combination with Pembrolizumab, is indicated for the treatment of adult patients with cancer of the advanced or recurrent endometrium, whose disease progresses during or following previous platinum-based chemotherapy received at any stage and who are not eligible for curative surgery or radiotherapy” [7].

PRES is one of the various side effects of LENVATINIB known before the authorization of the combination. PEMBROLIZUMAB has been implicated in the occurrence of autoimmune encephalitis for several years [8]. There is evidence of a link between PRES and humanized monoclonal antibody monotherapy, after a single dose, with onset usually within weeks of treatment [9]. Here we report a case of advanced endometrial cancer with neurological manifestations of PRES caused by the combination of LENVATINIB and PEMBROLIZUMAB. The patient has given informed consent for the publication of this case report, including the images.

Case Presentation

66-year-old patient with serous endometrial adenocarcinoma diagnosed in March 2021 in the context of peritoneal carcinomatosis. She initially received chemotherapy with 4 courses of CARBOPLATIN TAXOL between April and June 2022. Two additional courses were recommended following a Multidisciplinary Gynecology-Oncology Consultation Meeting and were carried out between July and August 2022. A dissociated response was noted, motivating the switch to second-line treatment with LENVATINIB and PEMBROLIZUMAB. Three cures were carried out from November 18 to December 29, 2022. From January 3, 2023, the patient presented with rapidly increasing headaches.

A cerebral CT scan, then a cerebral MRI were performed, finding areas of edema of the subcortical parieto-occipital white matter, predominantly on the right side, with a mass effect, in T1 hypointensity, with hyperintensity in FLAIR and hyperintensity in diffusion-weighted (DWI) without restriction of apparent coefficient diffusion (ADC), in favor of a PRES.

Figure 1: FLAIR and ADC from January 19, 2023.

She is transferred to the Neurology department. This was an awake patient, Glasgow 15, without neurological deficit, with a headache of 10/10 on the visual analogue scale. Blood work showed no significant alterations. Treatment with LENVATINIB and PEMBROLIZUMAB was stopped. It was noted a progressive regression of headaches with disappearance on the tenth day of hospitalization. Control cerebral MRIs were performed respectively on the seventh day after the onset of signs and two months later with regression of the lesions’extent.

Figure 2: FLAIR and ADC from january 26, 2023.