Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2023 Jul:187:25-35.
doi: 10.1016/j.ejca.2023.03.020. Epub 2023 Mar 23.

Discontinuation of anti-PD1 in advanced melanoma: an observational retrospective study from the Italian Melanoma Intergroup

Marco Rubatto  1 , Paolo Fava  2 , Ignazio Stanganelli  3 , Simone Ribero  2 , Jacopo Pigozzo  4 , Anna Maria Di Giacomo  5 , Laura Ridolfi  6 , Maria Chiara Tronconi  7 , Claudia Trojaniello  8 , Melissa Bersanelli  9 , Mattia Garutti  10 , Alice Indini  11 , Ivana De Risi  12 , Michele De Tursi  13 , Barbara Merelli  14 , Francesca Morgese  15 , Marcella Occelli  16 , Gian Carlo Antonini Cappellini  17 , Stefano Poletto  18 , Dahlia Fedele  19 , Sonia Brugnara  20 , Michela Frisinghelli  20 , Luigi Formisano  21 , Raffaele Conca  22 , Marco Tucci  23 , Michelangelo Russillo  24 , Luca Ceroni  25 , Paola Queirolo  26 , Giada Targato  27 , Sabino Strippoli  12 , Mario Mandalà  28 , Michele Guida  12 , Pietro Quaglino  2
Affiliations
Observational Study

Discontinuation of anti-PD1 in advanced melanoma: an observational retrospective study from the Italian Melanoma Intergroup

Marco Rubatto et al. Eur J Cancer. 2023 Jul.

Abstract

Background: Immunotherapy has improved the survival of patients with stage IV melanoma. In responders, clinical benefits may be long-lasting and persist even after treatment discontinuation. The optimal duration of anti-PD1 (anti-Programmed cell death-1) therapy in metastatic melanoma patients remains to be elucidated. Moreover, limited data are available on clinical outcomes of patients that discontinued anti-PD1 immunotherapy in a real-life setting. The aim of this study was to evaluate the progression-free survival (PFS) in patients with metastatic melanoma who interrupted anti-PD-1 treatment in the in the absence of disease progression.

Methods: We retrospectively reviewed patients with advanced/metastatic melanoma treated with anti-PD1 immunotherapy at 23 Italian Melanoma Intergroup (IMI) centres. The study investigated the risk of relapse in patients who stopped anti-PD1 therapy due to CR (Complete response), treatment-related toxicity, or by their own choice after a long period of treatment. Clinical and biological factors associated with or without recurrence were evaluated.

Results: The study population included 237 patients. The median age of patients was 68.9 years (standard deviation: 13; range 33-95). The median time on treatment was 33 months (standard deviation: 18, 7; range 1-98). Among the 237 patients, 128 (54%) interrupted the anti-PD1 for CR, 74 patients (31.2%) for adverse events (37 patients in CR, 27 patients in partial response (PR), ten patients in stable disease (SD), and 35 patients (14.8%) by their own choice (12 patients in CR, 17 patients in PR, and 6 patients in SD). After a mean follow-up of 21 months (range 1-81), PFS after anti-PD1 discontinuation was 85.7%. Thirty-four patients (14.3%) developed disease progression after a median of 12 months (range 1-35): ten patients (29.4%) after discontinuation in CR, 17 patients (50%) after discontinuation for treatment-related toxicity (seven in CR, five in PR, five in SD), and seven (20.6%) after discontinuation due to the patient's decision (two in CR, four in PR, one in SD). Only 7.8% of patients who interrupted in CR (10/128), along with 23% of patients who interrupted for limiting toxicity (17/74) and 20% of patients who interrupted by their own choice (7/35), developed recurrence. Regarding patients who discontinued therapy because of CR, we observed a negative association between recurrence and site of primary melanoma, especially mucosal sites (p = <0.05, HR (Hazard ratio) 15.57 IC (confidence interval) 95% 2.64-91.73). Moreover, M1b patients who achieved a CR showed a lower number of relapses (p = <0.05, HR 3.84 IC 95% 1.40-8.48).

Conclusions: This study shows in a real-life setting that, with anti-PD-1 therapy, long-lasting responses, can be maintained after anti-PD1 interruption. In 70.6% of cases, recurrences were observed among patients who did not obtain a CR at treatment discontinuation.

Keywords: Discontinuation of immunotherapy; Metastatic melanoma therapy; Real-life study.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marco Rubatto: nothing to declare, Paolo Fava: nothing to declare, Ignazio Stanganelli: nothing to declare, Simone Ribero: nothing to declare, Jacopo Pigozzo Advisory board BMS, MSD, Novartis, Anna Maria Di Giacomo: has served as a consultant and/or advisor to Incyte, Pierre Fabre, Glaxo Smith Kline, Bristol-Myers Squibb, Merck Sharp Dohme, Immunocore, SunPharma and Sanofi and has received compensated educational activities from Bristol-Myers Squibb, Merck Sharp Dohme, Pierre Fabre and Sanofi, Laura Ridolfi: nothing to declare, Maria Chiara Tronconi: nothing to declare, Claudia Trojaniello: sanofi, Melissa Bersanelli: nothing to declare, Mattia Garutti honoraria or consultation fees from Novartis, Eli Lilly, Pierre Fabre and Roche, and travel fees from Daichii Sankyo, all outside the submitted work, Alice Indini: nothing to declare, Ivana De Risi: nothing to declare, Michele De Tursi: nothing to declare, Barbara Merelli: nothing to declare, Francesca Morgese: nothing to declare, Marcella Occelli: nothing to declare, Gian Carlo Antonini Cappellini: nothing to declare, Stefano Poletto: nothing to declare, Dahlia Fedele: nothing to declare, Sonia Brugnara: nothing to declare, Michela Frisinghelli: nothing to declare, Luigi Formisano: LF has received research funding from Lilly outside the submitted work. LF is on the Advisory Board for Janssen-Cilag, Sanofi, MSD and BMS, Raffaele Conca: nothing to declare, Marco Tucci: nothing to declare, Michelangelo Russillo: nothing to declare, Luca Ceroni: nothing to declare, Paola Queirolo: nothing to declare, Giada Targato: nothing to declare, Sabino Strippoli: nothing to declare, Mario Mandalà: Advisory board and lectures for: MSD, BMS, Novartis, Pierre Fabre, Sanofi, Sun Pharma Research grant: Novartis, Michele Guida: nothing to declare, Pietro Quaglino: nothing to declare.

Publication types