Safety and efficacy of anti-PD-1 in patients with baseline cardiac, renal, or hepatic dysfunction

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.

Journal for immunotherapy of cancer. 2016 Oct 18*** epublish ***

Bridgette A Kanz, Megan H Pollack, Romany Johnpulle, Igor Puzanov, Leora Horn, Alicia Morgans, Jeffrey A Sosman, Suthee Rapisuwon, R Martin Conry, Zeynep Eroglu, Douglas B Johnson

Departments of Pharmaceutical Services, Vanderbilt Ingram Cancer Center, 2220 Pierce Avenue, Nashville, TN 37232 USA., Departments of Medicine, Vanderbilt Ingram Cancer Center, 777 PRB, 2220 Pierce Ave., Nashville, TN 37232 USA., Department of Medicine, Roswell Park Cancer Institute, Elm @ Carlton Streets, Buffalo, NY 14263 USA., Department of Oncology, Georgetown Lombardi Cancer Center, 3970 Reservoir Road NW, Washington, DC 20007 USA., Department of Medicine, University of Alabama at Birmingham, 1824 6th Avenue S, Birmingham, AL 35233 USA., Department of Cutaneous Oncology, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612 USA.