Durable clinical benefit in metastatic renal cell carcinoma patients who discontinue PD-1/PD-L1 therapy for immune-related adverse events (irAEs)

The current standard of care for treatment of metastatic renal cell carcinoma (mRCC) patients is PD-1/PD-L1 inhibitors until progression or toxicity. Here we characterize the clinical outcomes for 19 mRCC patients who experienced an initial clinical response (any degree of tumor shrinkage), but after immune-related adverse events (irAEs) discontinued all systemic therapy. Clinical baseline characteristics, outcomes, and survival data were collected. The primary end-point was time to progression from the date of treatment cessation (TTP). Most patients had clear cell histology and received anti-PD-1/PD-L1 therapy as second-line or later treatment. Median time on PD-1/PD-L1 therapy was 5.5 months (range: 0.7-46.5) and median TTP was 18.4 months (95% CI:4.7-54.3) per Kaplan-Meier estimation. The irAEs included arthropathies, ophthalmopathies, myositis, pneumonitis, and diarrhea. We demonstrate that 68.4% of patients (n = 13) experienced durable clinical benefit off treatment (TTP of at least 6 months), with 36% (n = 7) of patients remaining off subsequent treatment for over a year after their last dose of anti-PD-1/PD-L1. Three patients with tumor growth found in a follow-up visit, underwent subsequent surgical intervention, and remain off systemic treatment. Nine patients (47.4%) have ongoing irAEs. Our results show that patients who benefitted clinically from anti-PD-1/PD-L1 therapy can experience sustained beneficial responses, not needing further therapies after the initial discontinuation of treatment due to irAEs. Investigation of biomarkers indicating sustained benefit to checkpoint blockers are needed.

Cancer immunology research. 2018 Feb 01 [Epub ahead of print]

Dylan J Martini, Lana Hamieh, Rana R McKay, Lauren C Harshman, Raphael Brandao, Craig K Norton, John A Steinharter, Katherine M Krajewski, Xin Gao, Fabio A Schutz, Bradley McGregor, Dominick Bosse, Aly-Khan Lalani, Guillermo de Velasco, M Dror Michaelson, David F McDermott, Toni K Choueiri

Emory University School of Medicine., Dana-Farber Cancer Institute, Harvard Medical School., University of California San Diego., Beth Israel Deaconess Medical Center, Harvard Medical School., BP - A Beneficencia Portuguesa de Sao Paulo., Hospital Universitario 12 De Octubre., Massachusetts General Hospital, Harvard Medical School., Dana-Farber Cancer Institute, Harvard Medical School .