RARE-21. A DESCRIPTIVE REPORT OF PATIENTS WITH RARE CENTRAL NERVOUS SYSTEM (CNS) CANCERS ON AN NCI-CONNECT CANCER MOONSHOT IMMUNE CHECKPOINT INHIBITOR TRIAL Free

There is increasing interest in the use of immunotherapy in rare CNS tumors, but limited experiences in the clinical evaluation of imaging findings and treatment toxicity in these patients. A phase II clinical trial of Nivolumab, a PD-1 inhibitor, in eleven rare CNS tumors was developed by NCI-Connect program. The purpose of this report is to describe both patient-reported outcome (PRO) and standardized assessment of these patients treatment toxicities and correlate with imaging findings.

Patients were evaluated using standardized CTCAE (version 4.0) for toxicity grading and M.D. Anderson Symptom Inventory-Brain/Spine Tumor Module (MDASI-BT/SP) for PRO scoring. The item change scores (>1 point) in individual symptoms, overall symptom burden, and interference from symptoms were calculated at the time of imaging changes and classified as improved, stable or worsened.

Of thirteen patients, male (n=10), median age 43 (24–74), brain location (n=10), spine location (n=4), the most common diagnosis was Ependymoma (n=4). An average of 4 cycles of nivolumab was received, with three grade 3 or higher adverse events: one grade 3 colitis and two grade 3 lymphopenia. Radiographic disease progression was declared in all, confirmed by pathological diagnosis in 8/13. Per MDASI-BT/SP, mean symptom severity was stable in all cases; interference score was worse in 3/8 cases. Significant worsening in disease-related symptoms included walking (50%) and pain (25%). Autonomic function worsened in 2/3 spine patients; concentration/memory and seizures worsened in 60% and 20% respectively in brain tumor patients.

Nivolumab was well tolerated with no CNS specific adverse events. MRI changes were not associated with change in symptom burden, but was associated with significant worsening in patient-reported interference, specifically in walking, pain, seizures, cognitive or autonomic symptoms. Evaluation of cardinal symptoms associated with progression on immunotherapy may be meaningful diagnostic adjuncts in patients with rare CNS tumors.