Immunotherapy discontinuation in metastatic melanoma: Lessons from real-life clinical experience

Nethanel Asher*, Noa Israeli-Weller, Ronnie Shapira-Frommer, Guy Ben-Betzalel, Jacob Schachter, Tomer Meirson, Gal Markel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Immunotherapy has revolutionized outcomes for melanoma patients, by significantly prolonging survival and probably even curing a fraction of metastatic patients. In daily practice, treatment for responding patients is often discontinued due to treatment-limiting toxicity, or electively, following a major tumor response. To date, the criteria for a safe stop and the optimal duration of treatment remain unclear. Patients and methods: This is a real-world single-site cohort of 106 advanced melanoma patients who were treated with immunotherapy and who discontinued treatments in the absence of disease progression. Here, we describe their long-term outcomes, and analyze the differential characteristics between patients who ultimately experienced progression and those who remained in unmaintained durable response. Results: Patients were treated with anti-PD-1 monotherapy (81%) or in combination with ipilimumab (19%) for a median of 15.2 m (range, 0.7–42.3 m). Upon discontinuation, 75.5% had achieved a complete response (CR). After a median follow-up of 20.8 m (range, 6–58) from discontinuation, 32% experienced disease progression. Median time to progression was 8.5 m (range, 1.5–37). Response to re-induction with anti-PD-1 was observed in 47%. On multivariate analysis, achieving a non-CR response, immunotherapy given in advanced line, and shorter treatment duration were significantly associated with lesser progression-free survival. Conclusions: This is one of the few reports on real-world melanoma patients who discontinued immunotherapy while responding to treatment. This study reveals the key factors to bear in mind when considering an elective treatment cessation. Specifically, patients with non-CR as best response and patients treated in an advanced-line setting should be treated for longer periods, and elective discontinuation should not take place prior to 18 m.

Original languageEnglish
Article number3074
JournalCancers
Volume13
Issue number12
DOIs
StatePublished - 2 Jun 2021

Funding

FundersFunder number
Biond Biologicals
Medison
Samueli Foundation
Israel Science Foundation3495/19

    Keywords

    • Complete response
    • Immunotherapy
    • Melanoma
    • Treatment discontinuation

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