Small-Cell Lung Cancer with Positive Anti-NMDAR and Anti-AMPAR Antibodies Paraneoplastic Limbic Encephalitis.

We report the case of a 66-year-old woman, with paraneoplastic limbic encephalitis, treated 6 months earlier for bladder neoplasia. The patient presented to the emergency room with rapidly increasing symptoms, noninfectious cerebral spinal fluid associated with positive anti-NMDAR (as well as in serum) and positive AMPAR antibodies in the serum. Four months later, the patient was diagnosed with a small-cell lung cancer for which chemotherapy and radiotherapy was commenced. Simultaneously, endoscopic surgical treatment was undertaken for an in situ relapse of the bladder neoplasm. After the completion of 3 cycles of chemotherapy her neurological status temporarily worsened. The cerebral MRI did not show signs of encephalitis such as increased T2/FLAIR signal intensity in the mesial temporal lobes and limbic systems. No specific treatment was prescribed. Limbic encephalitis can be associated with malignant tumors such as lung carcinoma. Several cases reported in the literature have shown cognitive improvement after tumoral therapy. Regarding our experience, significant progress was achieved through immuno-modulatory treatment. A transitory deterioration of the cognitive process was perceived during the chemotherapy sessions.

First clinical results of a personalized immunotherapeutic vaccine against recurrent, incompletely resected, treatment-resistant glioblastoma multiforme (GBM) tumors, based on combined allo- and auto-immune tumor reactivity.

Glioblastoma multiforme (GBM) patients have a poor prognosis. After tumor recurrence statistics suggest an imminent death within 1-4.5 months. Supportive preclinical data, from a rat model, provided the rational for a prototype clinical vaccine preparation, named Gliovac (or ERC 1671) composed of autologous antigens, derived from the patient's surgically removed tumor tissue, which is administered together with allogeneic antigens from glioma tissue resected from other GBM patients. We now report the first results of the Gliovac treatment for treatment-resistant GBM patients. Nine (9) recurrent GBM patients, after standard of care treatment, including surgery radio- and chemotherapy temozolomide, and for US patients, also bevacizumab (Avastin™), were treated under a compassionate use/hospital exemption protocol. Gliovac was given intradermally, together with human GM-CSF (Leukine(®)), and preceded by a regimen of regulatory T cell-depleting, low-dose cyclophosphamide. Gliovac administration in patients that have failed standard of care therapies showed minimal toxicity and enhanced overall survival (OS). Six-month (26 weeks) survival for the nine Gliovac patients was 100% versus 33% in control group. At week 40, the published overall survival was 10% if recurrent, reoperated patients were not treated. In the Gliovac treated group, the survival at 40 weeks was 77%. Our data suggest that Gliovac has low toxicity and a promising efficacy. A phase II trial has recently been initiated in recurrent, bevacizumab naïve GBM patients (NCT01903330).