PMID- 32667663 OWN - NLM STAT- MEDLINE DCOM- 20210219 LR - 20210716 IS - 2168-6084 (Electronic) IS - 2168-6068 (Print) IS - 2168-6068 (Linking) VI - 156 IP - 9 DP - 2020 Sep 1 TI - Association of Anti-Programmed Cell Death 1 Antibody Treatment With Risk of Recurrence of Toxic Effects After Immune-Related Adverse Events of Ipilimumab in Patients With Metastatic Melanoma. PG - 982-986 LID - 10.1001/jamadermatol.2020.2149 [doi] AB - IMPORTANCE: Since 2011, many patients with metastatic melanoma have been treated with ipilimumab therapy and have developed severe immune-related adverse events (AEs). Because several immune therapies are now available to treat metastatic melanoma, a better knowledge of mechanisms and recurrence risks of immune-related AEs is needed before reintroduction of immunotherapies. OBJECTIVES: To evaluate the risk of a recurrence of immune toxic effects associated with anti-programmed cell death 1 antibody (anti-PD-1) therapy after discontinuation of ipilimumab monotherapy because of severe AEs. DESIGN, SETTINGS, AND PARTICIPANTS: This cohort study conducted at 19 French melanoma referral centers included patients with metastatic melanoma who experienced severe immune-related AEs after ipilimumab therapy and then were treated with anti-PD-1 therapy between February 1, 2013, and December 31, 2016. The study cutoff was June 1, 2017. Statistical analysis was performed from June 1, 2016, to August 31, 2017. EXPOSURES: Monotherapy with at least 1 cycle of ipilimumab that was associated with a grade 3 or 4 immune-related AE and subsequent treatment with at least 1 cycle of an anti-PD-1 (nivolumab or pembrolizumab) therapy. MAIN OUTCOMES AND MEASURES: The primary outcome was the rate of immune-related AEs associated with anti-PD-1 therapy. Secondary outcomes were characteristics of ipilimumab-related and anti-PD-1 immune-related AEs and overall response rate and overall survival associated with anti-PD-1 therapy. RESULTS: Of 56 patients with metastatic melanoma included in the study, all of whom experienced severe immune-related AEs after ipilimumab therapy (31 [55%] male; mean [SD] age, 64 [14.9] years), 20 (36%) experienced at least 1 immune-related AE associated with pembrolizumab (6 of 20 [30%]) or nivolumab (14 of 20 [70%]) therapy. A total of 12 patients (21%) experienced grade 3 or 4 immune-related AEs, and among these patients, 4 (33%) presented with the same immune-related AE as with ipilimumab therapy. Severe immune-related AEs were resolved with use of systemic corticosteroids (7 [58%]) and/or anti-tumor necrosis factor (1 [8%]), and no grade 5 toxic effects were reported. Five patients discontinued anti-PD-1 therapy because of immune-related AEs. The overall response rate was 43%, with a median overall survival of 21 months (interquartile range, 18 to ongoing). CONCLUSIONS AND RELEVANCE: The findings suggest that anti-PD-1 therapy may be associated with reduced risk of toxic effects and improved survival among patients who have experienced severe toxic effects after ipilimumab therapy. FAU - Brunot, Angelique AU - Brunot A AD - Department of Oncology, Comprehensive Cancer Center Eugene Marquis, Rennes, France. FAU - Grob, Jean-Jacques AU - Grob JJ AD - Department of Dermatology, University Hospital, Marseille, France. FAU - Jeudy, Geraldine AU - Jeudy G AD - Department of Dermatology, University Hospital, Dijon, France. FAU - Grange, Florent AU - Grange F AD - Department of Dermatology, University Hospital, Reims, France. FAU - Guillot, Bernard AU - Guillot B AD - Department of Dermatology, University Hospital, Montpellier, France. FAU - Kramkimel, Nora AU - Kramkimel N AD - Department of Dermatology, University Hospital, APHP Cochin, France. FAU - Mortier, Laurent AU - Mortier L AD - Department of Dermatology, University Hospital, Lille, France. FAU - Le Corre, Yannick AU - Le Corre Y AD - Department of Dermatology, University Hospital, Angers, France. FAU - Aubin, Francois F AU - Aubin FF AD - Department of Dermatology, University Hospital, Besancon, France. FAU - Mansard, Sandrine AU - Mansard S AD - Department of Dermatology, University Hospital, Clermont-Ferrand, France. FAU - Lebbe, Celeste AU - Lebbe C AD - Department of Dermatology, University Hospital, Assistance Publique Hopitaux Parsiens, Saint-Louis, France. FAU - Blom, Astrid AU - Blom A AD - Department of Dermatology, University Hospital, A. Pare Hospital, France. FAU - Montaudie, Henri AU - Montaudie H AD - Department of Dermatology, University Hospital, Nice, France. FAU - Giacchero, Damien AU - Giacchero D AD - Department of Dermatology, Comprehensive Cancer Center Lacassagne, Nice, France. FAU - Prey, Sorilla AU - Prey S AD - Department of Dermatology, University Hospital, Bordeaux, France. FAU - Legoupil, Delphine AU - Legoupil D AD - Department of Dermatology, University Hospital, Brest, France. FAU - Guyot, Alexis AU - Guyot A AD - Department of Dermatology, University Hospital, Avicenne, France. FAU - Amini-Adle, Mona AU - Amini-Adle M AD - Department of Dermatology, University Hospital, Lyon, France. FAU - Granel-Brocard, Florence AU - Granel-Brocard F AD - Department of Dermatology, University Hospital, Nancy, France. FAU - Meyer, Nicolas AU - Meyer N AD - Department of Dermatology, University Hospital, Toulouse, France. FAU - Dinulescu, Monica AU - Dinulescu M AD - Department of Dermatology, University Hospital, Rennes, France. FAU - Edeline, Julien AU - Edeline J AD - Department of Oncology, Comprehensive Cancer Center Eugene Marquis, Rennes, France. FAU - Campillo-Gimenez, Boris AU - Campillo-Gimenez B AD - Department of Oncology, Comprehensive Cancer Center Eugene Marquis, Rennes, France. FAU - Lesimple, Thierry AU - Lesimple T AD - Department of Oncology, Comprehensive Cancer Center Eugene Marquis, Rennes, France. LA - eng PT - Journal Article PL - United States TA - JAMA Dermatol JT - JAMA dermatology JID - 101589530 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (CTLA-4 Antigen) RN - 0 (CTLA4 protein, human) RN - 0 (Immune Checkpoint Inhibitors) RN - 0 (Ipilimumab) RN - 0 (PDCD1 protein, human) RN - 0 (Programmed Cell Death 1 Receptor) RN - 31YO63LBSN (Nivolumab) RN - DPT0O3T46P (pembrolizumab) SB - IM MH - Aged MH - Antibodies, Monoclonal, Humanized/administration & dosage/adverse effects MH - Brain Neoplasms/*drug therapy/immunology/mortality/secondary MH - CTLA-4 Antigen/antagonists & inhibitors/immunology MH - Drug-Related Side Effects and Adverse Reactions/diagnosis/*epidemiology/immunology/prevention & control MH - Female MH - Follow-Up Studies MH - Humans MH - Immune Checkpoint Inhibitors/administration & dosage/*adverse effects MH - Ipilimumab/administration & dosage/adverse effects MH - Kaplan-Meier Estimate MH - Male MH - Melanoma/*drug therapy/immunology/mortality/secondary MH - Middle Aged MH - Nivolumab/administration & dosage/adverse effects MH - Programmed Cell Death 1 Receptor/*antagonists & inhibitors/immunology MH - Recurrence MH - Response Evaluation Criteria in Solid Tumors MH - Retrospective Studies MH - Severity of Illness Index MH - Skin Neoplasms/*drug therapy/immunology/mortality/pathology PMC - PMC7364335 COIS- Conflict of Interest Disclosures: Dr Lebbe reported serving on the speaker's bureau for Roche, Novartis, Bristol-Myers Squibb, and Amgen; receiving research funding from Roche and Bristol-Myers Squibb; serving as an advisory board member for Roche, Amgen, Bristol-Myers Squibb, MSD, and Novartis; and receiving honoraria from Amgen, Bristol-Myers Squibb, Incyte, MSD, Novartis, Pfizer, Pierre Fabre, and Roche. Dr Edeline reported serving as an advisory board member for Bristol-Myers Squibb. Dr Lesimple reported serving on the speaker's bureau for and receiving honoraria from MSD, Novartis, Pierre Fabre, and Roche, and receiving research funding from Roche. No other disclosures were reported. EDAT- 2020/07/16 06:00 MHDA- 2021/02/20 06:00 PMCR- 2021/07/15 CRDT- 2020/07/16 06:00 PHST- 2020/07/16 06:00 [pubmed] PHST- 2021/02/20 06:00 [medline] PHST- 2020/07/16 06:00 [entrez] PHST- 2021/07/15 00:00 [pmc-release] AID - 2768255 [pii] AID - doi200041 [pii] AID - 10.1001/jamadermatol.2020.2149 [doi] PST - ppublish SO - JAMA Dermatol. 2020 Sep 1;156(9):982-986. doi: 10.1001/jamadermatol.2020.2149.