Outcomes following long-term response to immune checkpoint inhibitors in patients with advanced melanoma.

person Eleanor Handel The Crown Princess Mary Cancer Centre, Westmead, NSW, Australia info_outline Eleanor Handel, Janet McKeown, Joe Wei, Roma Kankaria, Hannah Burnette, Aleigha Lawless, Juliane Czapla, Lea Jessica Albrecht, Joanna Mangana, Jolien Isabel Kessels, Clara Allayous, Christina Ann Boatwright, Margaret Ottaviano, Anna Malgorzata Czarnecka, Piotr Rutkowski, Serigne N Lo, Georgina V. Long, Alexander M. Menzies, Matteo S. Carlino

Authors person Eleanor Handel The Crown Princess Mary Cancer Centre, Westmead, NSW, Australia info_outline Eleanor Handel, Janet McKeown, Joe Wei, Roma Kankaria, Hannah Burnette, Aleigha Lawless, Juliane Czapla, Lea Jessica Albrecht, Joanna Mangana, Jolien Isabel Kessels, Clara Allayous, Christina Ann Boatwright, Margaret Ottaviano, Anna Malgorzata Czarnecka, Piotr Rutkowski, Serigne N Lo, Georgina V. Long, Alexander M. Menzies, Matteo S. Carlino Organizations The Crown Princess Mary Cancer Centre, Westmead, NSW, Australia, Melanoma Institute Australia, Wollstonecraft, Australia, Vanderbilt-Ingram Cancer Center, Nashville, TN, Vanderbilt University Medical Center, Nashville, TN, Massachusetts General Hospital, Boston, MA, Department of Dermatology, University Hospital Essen, Germany, Essen, Germany, Department of Dermatology, University Hospital of Zurich, Zürich, Switzerland, Department of Medical Oncology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), Brussel, Belgium, APHP Hôpital Saint-Louis, Paris, France, Perlmutter Cancer Center, NYU Langone Health, New York, NY, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy, Italy, Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Mazowieckie, Poland, Maria Skłodowska-Curie National Institute of Oncology Center, Warsaw, Poland, Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia, Melanoma Institute Australia, The University of Sydney, Royal North Shore and Mater Hospitals, Sydney, NSW, Australia, Melanoma Institute Australia, Faculty of Medicine and Health, The University of Sydney, and Mater and Royal North Shore Hospitals, Sydney, NSW, Australia, Crown Princess Mary Cancer Centre, Sydney, NSW, Australia Abstract Disclosures Research Funding No funding sources reported Background: Immune checkpoint inhibitors (ICI) targeting PD-1 and CTLA-4 can achieve durable responses. Historically, therapies in advanced malignancies were considered palliative, however long-term results from ICI melanoma studies suggest cure may be possible for some patients (pts). Despite clinical trial data, little is known about the risk, character, and clinical outcome of late recurrences after ICI. Methods: ICI treated pts with advanced melanoma who had a long-term disease control, defined as not requiring a subsequent line of systemic therapy within 3 years, were retrospectively identified at 11 centres. Those who had progressive disease managed with local therapies were included if no new systemic therapy was commenced within the 3 years. Demographics, disease characteristics, treatment, toxicity, recurrence patterns, management and outcomes were collected. Results: 567 pts were identified, with a median follow up of 7 years since start of therapy. At ICI commencement, 41% and 17% had M1c or M1d disease respectively, 26% had an elevated LDH, 33% were BRAF mutant and 24% had received prior therapy. The ICIs received were anti-PD-1 +/- an investigational agent (59.3%), anti-PD-1 plus anti-CTLA-4 (35.8%), or an anti-CTLA-4 (5%). The median duration of therapy was 18 months, with 31% of pts stopping due to toxicity. 63 pts (11.1%) had oligo-progression within 3 years from ICI start. 53 pts (9.3%) had progression after 3 years, with median time to progression of 16.3 months. Subsequent late progression was more common in those who had oligo-progression within 3 years of treatment compared to those who had not (14/63, 22% vs 39/504, 7.7%, P<0.001). The risk of late progression was lower in those who achieved a complete response (CR) compared to those without a CR (23/369, 6.2% vs 30/198, 15.2%, P<0.001). The landmark 5 year PFS was 95% compared to 89% in those with or without a CR respectively. Duration of therapy, treatment cessation due to toxicity, or corticosteroid use were not associated with the risk of late progression. Most late progression occurred within year 3 to 5 (38/53, 72%). 15 pts who progressed after 3 years were managed with local therapy alone. In progressors retreated with PD-1 alone as the next subsequent therapy, 14 of 26 (54%) responded (7 CR, 7 PR). In the total cohort, there were 31 (5.5%) deaths, 7 (1.2%) from melanoma. Of the pts with a CR, 14 (3.7%) died, only 1 (0.3%) from melanoma. Of the 53 pts who progressed after 3 years, 10 (19%) died, 7 (13%) from melanoma. Conclusions: In this population of pts with advanced melanoma with long term disease control from ICI, the risk of subsequent disease progression and death was low (1.2%). Predictors for late progression after 3 years were a non-CR best response and prior progression within 3 years. This and other data suggest a significant proportion of long-term ICI responders are likely cured, and may inform frequency and duration of follow up.