LAUSR

Patients with glioblastoma (GBM) have a poor prognosis following an extensive resection, radiotherapy (RT) and concomitant/adjuvant temozolomide (TMZ). Once GBM progresses after SOC, lomustine is the standard second-line treatment, while rechallenge with TMZ may be employed in selected patients with methylated promoter of MGMT, and bevacizumab is reserved for patients with extensive edema and need for steroids. New treatment modalities have been investigated at first recurrence, including alternating electric fields (TTFields) or antibody direct against epidermal growth factor receptor (EGFR), such as depatuximab mafodontin (ABT-414, Depatux-M), that have shown some activity in terms of disease control and progression-free survival (PFS). In September 2018, a 38 year-old man developed reduced strength in left upper limb and daily focal seizures. MRI showed an enhancing right fronto-temporal lesion which was subtotally removed with a diagnosis of glioblastoma (IDH 1/2 wild type, MGMT methylated - 40%, EGFR amplified, EGFRvIII positive). As the patient had a poor KPS (50), in October 2018 a hypofractionated RT (DFT 40 Gy/15 fractions) with concomitant TMZ (140 mg/day) was performed, followed by adjuvant standard TMZ (340 mg/day); however, chemotherapy was stopped after 3 cycles due to local progression on MRI coupled with strength worsening, increased seizure frequency, and need for steroids. Pseudoprogression was ruled out due to tumor growth out of the field of RT. Based on the high level of methylation of the MGMT promoter and EGFR amplification, a combined treatment with metronomic TMZ (100 mg/day continuously) plus Depatux-M (1.25 mg/kg every 2 weeks) was started (February 2019), but a brain MRI performed after 3 months of treatment displayed no significant changes on both MRI and neurological status. At this time point (May 2019) TTFields treatment was added. An initial decrease of tumor size was observed on MRI after 5 months, while a reduction of tumor size more than 90% has been progressively achieved after 1 year of treatment (April 2020). Moreover, a seizure-free status was observed without changing the antiepileptic medication. The patient developed a grade 3 ocular side effect (CTCAE version 5.0) with photophobia, blurred vision, foreign body sensation in the eyes after 6 months of treatment, which improved after dose delays and dose reduction of Depatux-M. The patient is still alive, and free of progression after 30 months and 25 months from diagnosis and first recurrence, respectively. To our knowledge, this is the first report of a recurrent GBM with a significant and long-lasting neuroradiological response following a combined treatment with TTFields, Depatux-M, and intensified schedule of TMZ. A synergistic effect of TTFields with compounds interfering with the microtubular system should be further investigated.