No abstract

BACKGROUND: Immune checkpoint blockade has shown significant antitumor responses and is approved for the treatment of multiple cancer types. Immune checkpoint inhibitors (ICI) are associated with a unique set of toxicities termed irAEs. This study seeks to review the incidence and clinical manifestations of patients who developed neuro-toxicity with ICIs. METHODS: An IRB approved retrospective study involved review of charts and institutional databases. We identified patients who developed neurotoxicity while on at least one of the following ICIs: anti-CTLA4, anti-PD1 or anti-PD-L1 over a 6 year period (1/1/2010-5/15/2016). RESULTS: We identified a total of 3,804 patients who were treated with one or more ICI during the period of review. Neuro-toxicity was observed in 99 patients (2.6%) affecting both central and peripheral nervous systems. 35 patients (34.7%) received more than one ICI. Median number of cycles prior to developing toxicity was 3 (1-29). Ten patients had more than 1 neuro-toxicity. The various neurologic phenotypes observed in patients included: Sensory neuropathy (34), encephalopathy (18), headache (16), aseptic meningitis (13), Myasthenia Gravis like syndrome (6), myopathy (6), autonomic neuropathy (5), aphasia syndromes (3), radiculopathy (2), brachial plexitis (2), mononeuritis multiplex (2), AIDP (1), and PRES (1). 58 patients required hospital admission and 2 required ICU level of care. A diagnosis of neuro-toxicity was based upon the temporal association with ICIs and appropriate workup including but not limited to neurologic consultation, lumbar puncture, and neuro-imaging. Patients were treated with drug holiday, observation, corticosteroids, plasmapheresis and/or IVIG. CONCLUSIONS: As ICI's are being used with increased frequency, treating oncologists should be aware of the varied manifestations of neuro-toxicity in order to ensure appropriate diagnosis, work up and treatment. Prompt treatment may relay a benefit in regards to outcome.

Newly diagnosed GBM patients experience challenges to maintain their health related QoL throughout the disease course. Disease-and treatmentrelated factors impact health related QoL. We sought to evaluate the trajectory of health related QoL in newly diagnosed glioblastoma patients treated with bevacizumab at diagnosis, through the disease course, and beyond progression. In this prospective single-center study, newly diagnosed subjects with GBM were treated with concurrent radiation and temozolomide plus bevacizumab followed by adjuvant temozolomide and bevacizumab. At progression, bevacizumab use was continued but chemotherapy could be changed per the treating neuro-oncologist recommendation. Health related QoL was evaluated using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) at time of study enrollment (before chemoradiation), after chemoradiation, and then every 6 mos until study discontinuation or subject demise. Higher scores on the FACT-Br correspond to better QoL. 68 newly diagnosed GBM patients were enrolled with a mean age of 55.4 yrs (sd=10.7 yrs). KPS ranged 70-100 with the following distribution: 70 (n=4), 80 (n=28), 90 (n=34), and 100 (n=2). FACT-Br scores were relatively maintained from baseline evaluation (mean=96.71, sd=17.64) to 20 months from baseline (mean=100.68, sd=22.12). Subjects who continued study participation 6 mos after the completion of chemoradiation were divided into two groups: subjects with (n=16) and without (n=35) tumor progression 6 mos after chemoradiation completion. Regardless of disease progression, both groups maintained QoL (with progression baseline (mean=98.06, sd=17.18) and 14 months from baseline (mean=91.80, sd 7.16) and without progression baseline (mean=96.34 sd=17.09) and 14 months from baseline (mean=96.75, sd=24.95)). Our observations of health related QoL throughout the disease course and beyond progression suggest that health related QoL can be maintained in GBM patients treated with bevacizumab. Continued evaluation of health related QoL throughout the disease course is warranted in the evaluation of novel treatment regimens in GBM.