title: Safety and efficacy of anti-PD-1 in patients with baseline cardiac, renal, or hepatic dysfunction.
abstract: Anti-PD-1 therapy is increasingly used in various advanced malignancies. Patients with baseline organ dysfunction are largely excluded from clinical trials. Therefore it is unclear whether anti-PD-1 therapy is safe or effective in this setting. Further, these patients are often not candidates for other anti-cancer therapies, highlighting their need for active treatment options.
  
  
  
  We performed a retrospective analysis of patients from multiple centers with advanced solid tumors and baseline organ dysfunction who received anti-PD-1 therapy. Organ dysfunction was defined as cardiac (left ventricular ejection fraction ≤45 %), renal (creatinine ≥2 mg/dL or GFR ≤30 ml/min) or hepatic dysfunction (evidence of cirrhosis on imaging or AST, ALT or bilirubin ≥3x ULN). We assessed change in organ dysfunction, immune related adverse events (irAEs), response rate, progression free survival (PFS) and overall survival (OS).
  
  
  
  We identified 27 patients eligible for inclusion with the following diseases: renal cell carcinoma (n= 8), melanoma (10), non-small cell lung cancer (3), small cell lung cancer (2) and urothelial bladder cancer (4). Baseline organ dysfunction included renal dysfunction (n= 17), hepatic dysfunction (7), cardiac dysfunction (11), including >1 organ dysfunction (8). Worsening organ dysfunction requiring hospitalization or dose delays occurred in 8 patients (30 %) although in most cases this was thought not-drug related and resolved with supportive care. Grade 3 irAEs occurred in 2 pts (7 %; hepatitis and colitis). Thirteen of 27 patients had ongoing treatment benefit (objective response or stable disease) at data collection (48 %). Eleven patients had primary progressive disease (41 %), 11 had stable disease (41 %), 4 had partial responses (15 %), and one had a complete response (4 %). Overall, median PFS was 168 days. Median OS was not reached.
  
  
  
  In our experience, anti-PD-1 agents in this group of patients with cardiac, hepatic or renal dysfunction were associated with tolerable irAEs and infrequent manageable worsening of organ dysfunction. Further, objective responses and prolonged PFS were observed in a number of patients. Thus, patients with baseline organ dysfunction may be considered for anti-PD-1 therapy with appropriate clinical monitoring.
authors: Departments of Pharmaceutical Services, Vanderbilt Ingram Cancer Center, 2220 Pierce Avenue, Nashville, TN 37232 USA.
authors: Bridgette A
authors: BA
authors: Kanz
authors: Departments of Pharmaceutical Services, Vanderbilt Ingram Cancer Center, 2220 Pierce Avenue, Nashville, TN 37232 USA.
authors: Megan H
authors: MH
authors: Pollack
authors: Departments of Medicine, Vanderbilt Ingram Cancer Center, 777 PRB, 2220 Pierce Ave., Nashville, TN 37232 USA.
authors: Romany
authors: R
authors: Johnpulle
authors: Department of Medicine, Roswell Park Cancer Institute, Elm @ Carlton Streets, Buffalo, NY 14263 USA.
authors: Igor
authors: I
authors: Puzanov
authors: Departments of Medicine, Vanderbilt Ingram Cancer Center, 777 PRB, 2220 Pierce Ave., Nashville, TN 37232 USA.
authors: Leora
authors: L
authors: Horn
authors: Departments of Medicine, Vanderbilt Ingram Cancer Center, 777 PRB, 2220 Pierce Ave., Nashville, TN 37232 USA.
authors: Alicia
authors: A
authors: Morgans
authors: Departments of Medicine, Vanderbilt Ingram Cancer Center, 777 PRB, 2220 Pierce Ave., Nashville, TN 37232 USA.
authors: Jeffrey A
authors: JA
authors: Sosman
authors: Department of Oncology, Georgetown Lombardi Cancer Center, 3970 Reservoir Road NW, Washington, DC 20007 USA.
authors: Suthee
authors: S
authors: Rapisuwon
authors: Department of Medicine, University of Alabama at Birmingham, 1824 6th Avenue S, Birmingham, AL 35233 USA.
authors: R Martin
authors: RM
authors: Conry
authors: Department of Cutaneous Oncology, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612 USA.
authors: Zeynep
authors: Z
authors: Eroglu
authors: Departments of Medicine, Vanderbilt Ingram Cancer Center, 777 PRB, 2220 Pierce Ave., Nashville, TN 37232 USA.
authors: Douglas B
authors: DB
authors: Johnson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000074322:Antineoplastic Agents, Immunological / Q000009:adverse effects* / Q000627:therapeutic use; D066126:Cardiotoxicity; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006334:Heart Function Tests; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007677:Kidney Function Tests; D008099:Liver / Q000187:drug effects* / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D009367:Neoplasm Staging; D009369:Neoplasms / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D000072078:Positron Emission Tomography Computed Tomography; D061026:Programmed Cell Death 1 Receptor / Q000008:administration & dosage*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000074322:Antineoplastic Agents, Immunological; D061026:Programmed Cell Death 1 Receptor
keywords: Anti-PD-1; Cardiac; Dysfunction; Hepatic; Melanoma; Nivolumab; Organ; Pembrolizumab; Renal