Abdul Rafeh Naqash

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 4 mg/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 23 mg/L (range 0.1–238.5) at baseline to 109.3 mg/L (21.5–350.4) at the time of index irAE, followed by a decrease to 19.2 mg/L (0.25–149) after tocilizumab (p < 0.00001). 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

Hemophagocytic lymphohistiocytosis (HLH) secondary to Ehrlichia chaffeensis with bone marrow involvement

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.

Metastatic melanoma in a 95 years old patient responding to treatment with talimogene laherparepvec followed by nivolumab

Dear Editor, Hemophagocytic lymphohistiocytosis (HLH) is a rare lifethreatening clinical syndrome of hyper inflammation that leads to a dysregulated and ineffective immune activation [1]. Patients can often present similar to a sepsis-like syndrome with multi-organ dysfunction, and despite treatment, a high mortality rate is observed [2]. HLH is classified as primary or familial when a gene mutation is identified and secondary or sporadic in its absence. Common triggers for either entity include infections, the most common being Epstein-Barr virus, and immunodeficiency states like inherited syndromes, malignancy, autoimmune disorders, or HIV infection [1, 2]. Very little is known about Ehrlichia as an etiology for HLH. We present a rare case of secondary HLH due to Ehrlichia chaffeensis (E. chaffensis) with bone marrow involvement in a patient with HIV. A 66-year-old African American female with a history of HIV and noncompliance with anti-retroviral medications presented with septic shock requiring vasopressors. On admission, the temperature was 38.2 °C; heart rate was in the 140 s; examination was remarkable for lethargy and diffuse abdominal pain. A computed tomography scan of the abdomen/ pelvis was unrevealing. Complete blood count was notable for pancytopenia with a white cell count of 3.0 × 10/μl, platelet count of 22 × 10/μl, and hemoglobin of 12.2 g/dl. Metabolic profile demonstrated multi-organ dysfunction with serum creatinine elevated at 4.89 mg/dl and transaminitis with AST of 132 U/L and ALT of 518 U/L. Both CD-4 and CD-56 NK cells were 0.00/μl. HIV viral load was 8113 copies/ml. Serum triglycerides were elevated at 358 mg/dl. Ferritin was > 40,000 ng/ml. She was empirically started on broad spectrum antibiotics along with liposomal amphotericin-B. Due to her clinical presentation and the

Interleukin-6 as one of the potential mediators of immune-related adverse events in non-small cell lung cancer patients treated with immune checkpoint blockade: evidence from a case report

thrombosis and bile duct stenosis after stereotactic body radiation therapy for hepatocellular carcinoma. Hepatol Res. 2014;44:E278. [11] Nery F, Chevret S, Condat B, et al. Causes and consequences of portal vein thrombosis in 1,243 patients with cirrhosis: results of a longitudinal study. Hepatology. 2015;61:660–667. [12] Harding DJ, Perera MT, Chen F, et al. Portal vein thrombosis in cirrhosis: controversies and latest developments. World J Gastroenterol. 2015;21:6769. [13] Seppenwoolde Y, Wunderink W, Wunderink-van Veen SR, et al. Treatment precision of image-guided liver SBRT using implanted fiducial markers depends on marker-tumour distance. Phys Med Biol. 2011;56:5445. [14] Chan MKH, Lee V, Chiang CL, et al. Lipiodol versus diaphragm in 4D-CBCT-guided stereotactic radiotherapy of hepatocellular carcinomas. Strahlenther Onkol. 2016;192:92–101. [15] Szeto A, Chin L, Whelan P, et al. Image-guided radiation therapy using surgical clips for localization of colonic metastasis from thyroid cancer. Radiat Oncol. 2014;9:298. [16] Anantharaju A, Van Thiel DH. Liver transplantation for alcoholic liver disease. Alcohol Res Health. 2003;27:257–268.

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

both NRH and iMCD. Clinical features of Castleman’s disease are extremely heterogeneous, ranging from mild flu-like symptoms to vascular leak syndrome, organ failure and even death [6]. However, severe life-threatening hepatic presentations are exceedingly rare. To our knowledge, there are only two other case reports of NRH in patients with MCD [4,5]. Molina et al. describe a case of MCD who died after an acute UGB, possibly in the context of portal hypertension (even though esophageal varices were not found). He was initially treated with corticosteroids, which he did not tolerate, and were eventually suspended. Autopsy revealed features compatible with NRH [5]. Kiyuna et al. report a woman with NRH and MCD, treated with corticosteroids, with clinical improvement. Notably, she did not present signs of portal hypertension [4]. There is an additional case reported by Abarca et al. who, despite not having NRH, also presented MCD and portal hypertension, with a fatal result due to hepatorenal syndrome. This patient presented with UGB due to esophageal varices [2]. Our patient presented a more favorable outcome comparing to the other reports of MCD and concomitant portal hypertension. None of the other cases in the literature were treated with CHOP. Cytotoxic lymphoma based chemotheraphies are known to induce responses in severely ill iMCD patients [7], with long-term remissions reported in up to 25% of cases [8]. Newer therapies, such as siltuximab, an anti-interleukin 6 (IL-6) monoclonal antibody are now recommended [9,10], in light of the known association between Castleman’s disease and IL-6 [11]. Additionally, transgenic mice expressing high level of IL-6 have developed NRH, similar to human NRH [12]. Anti-IL6 therapy was not available at the time, and since the patient is currently stable, we have not medicated him further. In conclusion, we describe an unusual association of iMCD with non-cirrhotic portal hypertension due to NRH, with a good outcome after CHOP, which had not yet been reported as a treatment option for this unique constellation of conditions.

4A.03 Predictive Utility of c-reactive Protein (CRP) in Advanced Stage Lung Cancer Treated with Anti-Programmed Cell Death-1 (PD-1) Therapy: 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