Drug-Induced Aseptic Meningitis Associated With Intrathecal Trastuzumab

Abstract

To report a case of drug-induced aseptic meningitis (DIAM) in a patient receiving intrathecal trastuzumab (ITT) for leptomeningeal carcinomatosis (LC) secondary to HER-2/neu positive breast cancer. Case Summary: A 43-year-old female with stage IV breast cancer presented with headache, parasthesias, and aphasia. Brain imaging suggested leptomeningeal enhancement. Adenocarcinoma cells were found on cerebrospinal fluid analysis, and infectious etiologies were excluded. The patient received 30 mg of ITT via Ommaya reservoir and suffered sudden neurologic deterioration within 2 hours. Given the sudden onset of clinical deterioration after ITT administration, it was determined that the patient had suffered from DIAM. The patient suffered progressive neurologic decline and was unable to care for herself any further. Discussion: Treatment for LC remains challenging due to limited clinical experience and the challenging location of the disease. ITT has been used in multiple reports without adverse events. A temporal relationship existed between ITT administration and significant neurologic deterioration, possibly related to DIAM. Our patient was not exposed to any more common causative agents of DIAM. Reasons for her lack of recovery are likely multifactorial. Symptoms of DIAM may have in part been exacerbated by progressive LC; however, prior to ITT, symptoms had shown slow but persistent progression rather than significant, acute changes in severity. Retrial of the offending agent was not attempted due to patient risk; thus, a cause-and-effect relationship cannot be established. This event is a "possible" drug-induced adverse event scoring 2 on the Naranjo algorithm. Conclusions: Use of ITT for LC has been frequently reported in recent literature with substantial efficacy and lack of adverse events. This is the first published report of any significant adverse event associated with ITT. Clinicians need to be aware of the possibility of DIAM with ITT and explore options to prevent or manage this severe complication.

Intrathecal Therapy Options for Meningeal Carcinomatosis

“…These occurred in 5% of cases [17]. Independently from one another, Freyer et al and Pappa et al reported the occurrence of drug-induced aseptic meningitis, probably induced by trastuzumab [16,21]. Following the diagnosis of drug-induced aseptic meningitis, Freyer et al discontinued treatment with intrathecal trastuzumab in a 43-year-old patient.…”

“…Vier Studien beschäftigen sich mit der Verwendung von IT Trastuzumab bei HER2-positiven Mammakarzinomen als Primärtumor [15,16,17,21] [15,17]. In der Metaanalyse wurden in 87,9% der Fälle keine schwerwiegenden unerwünschten Ereignisse verzeichnet.…”

“…1 zu entnehmen. [13,17,21,22]. Vier Studien machten keine weitere Angabe zu dem verwendeten Applikationsverfahren [12,15,19,23].…”

Intrathecal Trastuzumab as a Potential Cause of Drug-Induced Aseptic Meningitis

“…6 Interestingly, we found another case of drug-induced aseptic meningitis attributed to IT trastuzumab. 7 However, in the previous case, it was decided to stop IT trastuzumab and the patient suffered progressive neurologic decline. 7 Remarkably, both cases have a similar drug-induced aseptic meningitis potentially associated with IT trastuzumab.…”

“…7 However, in the previous case, it was decided to stop IT trastuzumab and the patient suffered progressive neurologic decline. 7 Remarkably, both cases have a similar drug-induced aseptic meningitis potentially associated with IT trastuzumab. However, we decided to resume the treatment due to the riskbenefit ratio and the lack of other therapeutic alternatives.…”