Aparna Madhukeshwar Hegde

Tocilizumab for the management of immune mediated adverse events secondary to PD-1 blockade

Background Immune checkpoint inhibitors are poised to revolutionize the management of a growing number of malignancies. Unfortunately, the management of steroid-refractory immune mediated adverse events is based on a paucity of randomized data and limited to single center experiences. Our initial experience with the IL-6 receptor antagonist tocilizumab showed clinical improvement in a wide variety of irAEs. As a result, we adopted the use of tocilizumab for the management of steroid refractory irAEs. Methods The character and clinical course of irAEs were abstracted from the medical record and analyzed. The dose of tocilizumab was 4u2009mg/kg given IV over one hour. C-reactive protein was drawn at first nivolumab infusion and at q two weeks (and with irAEs) thereafter. Clinical improvement was defined as either: documentation of resolution of symptoms or hospital discharge within seven days. Results Of the initial 87 patients that were treated with nivolumab, 34 required tocilizumab (39.1%). All patients were on corticosteroids. The majority (88.2%) were lung cancer patients. The index grade 3/4 irAE was pneumonitis in 35.3%, serum sickness/SIRS in 35.3%, cerebritis in 14.7% and one case each of hypophysitis, colitis, pancreatitis, hepatitis and immune mediated coagulopathy. Median time between first nivolumab and initiation of tocilizumab was 76 days (range 1–429). There was a statistically significant increase in C-reactive protein from a median of 23u2009mg/L (range 0.1–238.5) at baseline to 109.3u2009mg/L (21.5–350.4) at the time of index irAE, followed by a decrease to 19.2u2009mg/L (0.25–149) after tocilizumab (pu2009<u20090.00001). Clinical improvement was noted in 27/34 patients (79.4%). Some patients (52.9%) required a single dose, while 38.2% required two, 8.8% required three and 1 patient required four doses. Twenty-seven doses were given in the inpatient setting (49.1%). Median time to discharge was four days (range 1–27). Seventy-four percent of patients were discharged home. For the 53 doses of tocilizumab that were delivered when infliximab was an option, there was a cost savings of

Co-relation of overall survival with peripheral blood-based inflammatory biomarkers in advanced stage non-small cell lung cancer treated with anti-programmed cell death-1 therapy: results from a single institutional database

141,048.72 (WAC) during the 18 month study period. Conclusions Tocilizumab may be a therapeutic option for the management of steroid refractory irAEs secondary to immune checkpoint blockade. However, randomized trials are needed to better elucidate the relative efficacy and safety of these agents.

PS01.64: Effect of Anti-PD1 Therapy on the Incidence of Thromboembolic Events in Lung Cancer: Topic: Medical Oncology

Abdul Rafeh Naqash , Chipman Robert Geoffrey Stroud, Muhammad Umer Butt, Grace K. Dy, Aparna Hegde, Mahvish Muzaffar, Li V. Yang, Maida Hafiz, Cynthia R. Cherry and Paul R. Walker Division of Hematology/Oncology, East Carolina University, Greenville, NC, USA; Division of Cardiovascular Research, University of Kentucky Medical Center, Lexington, KY, USA; Department of Thoracic Oncology, Roswell Park Cancer Center, Buffalo, NY, USA; Department of Internal Medicine, East Carolina University, Greenville, NC, USA; Department of Thoracic Oncology, East Carolina University, Greenville, NC, USA

Sequence of stereotactic ablative radiotherapy and immune checkpoint blockade in the treatment of metastatic lung cancer.

Background: The development of programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) checkpoint inhibitors has changed the landscape of nonesmall cell lung cancer (NSCLC) therapy, with 2 approvals from the US Food and Drug Administration of PD-1 inhibitors for second-line therapy. Information regarding relapse patterns, however is limited. This study investigates the the incidence, timeframe, and clinical features of acquired resistance to anti-PD-1/PD-L1 therapy. Methods: We collected retrospective data on 37 NSCLC patients treated at the University of Chicago Cancer Center from 2011-2016 with either Nivolumab or Pembrolizumab monotherapy. Acquired resistance was defined as patients who achieved initial partial or complete response (PR/CR) measured by RECIST v1.1 criteria followed by progression after initial response. Results: From this cohort, median age was 68.2, 22/37 (59%) had adenocarcinoma histology, and 18/37 (48%) were males. All patients had a prior smoking history (average of 40 pack years). 35 patients were treated with nivolumab, 2 patients with pembrolizumab. PR and SD were achieved in 14 (37.8%) and 9 (24.3%) of patients, respectively (overall clinical benefit rate was 62%). Median PFS was 6.3 months, while median OS was not reached. Best median RECIST change in tumor size for all PR and SD treated patients was 22.5%. Of the patients with SD or PR, 7/23 (30.4%) acquired resistance. For these patients, all had an ECOG score of 1-2 and 5/7 had received 2 lines of prior therapy. Five patients had squamous histology, two patients had adenocarcinoma. The two adenocarcinoma patients both had KRAS mutations (A146T and G12C). There was a 20.5% increase in tumor size from best median RECIST response. Median PFS was 6.30 months (1.3 months e 8.7 months). All patients had progression of existing lesions, rather than new lesions. Conclusion: We observed 30.4% of patients who initially had a clinical benefit develop resistance to antiPD-1/PD-L1 therapy with a median PFS of 6.3 months (1.3 months e 8.7 months). These occurred in patients with squamous histology or KRAS-mutant adenocarcinoma histology. In all cases, this was characterized by progression of prior lesions, rather than new lesions. Further studies are needed to fully characterize patterns of relapse and molecular characteristics of these patients.