Moderate Colitis Not Requiring Intravenous Steroids Is Associated with Improved Survival in Stage IV Melanoma after Anti-CTLA4 Monotherapy, But Not Combination Therapy.

Autor: Anstadt EJ; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA., Chu B; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Yegya-Raman N; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA., Han X; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA., Doucette A; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA., Poirier K; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA., Mohiuddin JJ; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA., Maity A; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA., Facciabene A; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA., Amaravadi RK; Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Karakousis GC; Division of Endocrine and Oncologic Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA., Cohen JV; Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Mitchell TC; Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Schuchter LM; Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Lukens JN; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA.
Jazyk: angličtina
Zdroj: The oncologist [Oncologist] 2022 Sep 02; Vol. 27 (9), pp. 799-808.
DOI: 10.1093/oncolo/oyac108
Abstrakt: Background: For patients with melanoma, gastrointestinal immune-related adverse events are common after receipt of anti-CTLA4 therapy. These present difficult decision points regarding whether to discontinue therapy. Detailing the situations in which colitis might predict for improved survival and how this is affected by discontinuation or resumption of therapy can help guide clinical decision-making.
Materials and Methods: Patients with stage IV melanoma receiving anti-CTLA4 therapy from 2008 to 2019 were analyzed. Immune-related colitis treated with ≥50 mg prednisone or equivalent daily or secondary immunosuppression was included. Moderate colitis was defined as receipt of oral glucocorticoids only; severe colitis was defined as requiring intravenous glucocorticoids or secondary immunosuppression. The primary outcome was overall survival (OS).
Results: In total, 171 patients received monotherapy, and 91 received dual checkpoint therapy. In the monotherapy group, 25 patients developed colitis and a nonsignificant trend toward improved OS was observed in this group. Notably, when colitis was categorized as none, moderate or severe, OS was significantly improved for moderate colitis only. This survival difference was not present after dual checkpoint therapy. There were no differences in known prognostic variables between groups, and on multivariable analysis neither completion of all ipilimumab cycles nor resumption of immunotherapy correlated with OS, while the development of moderate colitis did significantly affect OS.
Conclusion: This single-institution retrospective series suggests moderate colitis correlates with improved OS for patients with stage IV melanoma treated with single-agent anti-CTLA4, but not dual agent, and that this is true regardless of whether the immune-checkpoint blockade is permanently discontinued.
(© The Author(s) 2022. Published by Oxford University Press.)
Databáze: MEDLINE