Jessica Hardin

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

PS01.36: Blood-Based Mutation Testing in Non–Small Cell Lung Carcinoma Patients Supports Individualized and Optimal Treatment: Topic: Medical Oncology

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.

OA03.05 Tocilizumab for the Management of Immune Mediated Adverse Events Secondary to PD-1 Blockade: Overall Survival Analysis: Topic: Medical Oncology

Background: As the molecular genotypes of NSCLC expands, the strategy of treatment changes. EGFR exon 19 deletions and 21 mutations have different optimal treatment approaches. EGFR T790M mutations can now be targeted and may be immunogenic epitopes. KRAS mutations have different platinum, taxane and pemetrexed sensitivities. ALK is the most prevalent driver mutation in young people under the age of 40 and is often pharmacogenomically platinum resistant. ALK has a very high predilection for central nervous system metastases which can now be targeted with tyrosine kinase inhibitors (TKI) with high CNS penetrance and effectiveness. BRAF V600E mutations benefit from dual BRAF and MEK TKIs as in melanoma. Tissue quantity and lengthy turnaround time for tissue-based mutation results greatly impact and delay the optimal individualization of treatment in NSCLC with ultimate outcomes greatly impacted if treatment with an actionable targeted TKI is not received. We sought mutation testing that would allow our institution to identify actionable mutations quickly and to insure an actionable mutation status was known on all patients. Methods: Our institution has been prospectively collecting blood samples from NSCLC patients from March 2016 and submitting them for testing on the commercially available GeneStrat platform. Patients were tested for EGFR, ALK, KRAS and BRAF mutations using previously-described ddPCR methods. Blood samples were drawn at either their diagnostic bronchosocpy or at their first consultation interaction. Results: Blood samples from 62 patients were collected and submitted for GeneStrat testing. Results were available within 72 hours of blood draw for all of patients. 12 out of 62 patients had actionable mutations; 1 patient (pt.) EGFR exon 19, 1 pt. with exon 19 and exon 20 T790M, 2 pts. EGFR exon 20 T790M, 1 pt. exon 21 L858R, 1 pt. BRAF V600E, 2 pts. KRAS G12C, 2 pts. KRAS G12D, 1 pt. KRAS G12V and 1 pt. EMLA4-ALK mutations were identified. If platinum doublet chemotherapy was arbitrarily given, the initial treatment for these patients would have been suboptimal, not individualized and delayed awaiting tissue actionable mutation results and possible repeated biopsy attempts. Conclusion: Blood-based mutation testing with GeneStrat optimized and individualized treatment in one out of five of our institution’s NSCLC patients without the need for repeat tissue biopsies.