{
  "abstract": "Background Immune checkpoint inhibitors (ICIs) are the preferred systemic therapy for most patients with advanced Merkel cell carcinoma (MCC). However, the optimal duration of treatment for patients responding to ICI is unclear. Emerging data from retrospective analyses indicate a higher risk of MCC progression after ICI discontinuation, as compared with continuing ICI.Methods We performed a retrospective cohort study to evaluate the rate of progressive disease (PD) after treatment discontinuation in patients with advanced MCC who experienced objective responses to first-line ICI. We evaluated whether the risk of PD was associated with the reason for treatment discontinuation (elective vs due to toxicity) and depth of response (complete vs partial response (CR vs PR)).Results Among 105 responders, 58 discontinued ICI (median treatment duration: 12 months), and 47 continued ICI (median treatment duration: 20 months) at data cut-off. With a median follow-up of 34 months from ICI initiation, 33% of the entire cohort experienced disease progression at 2 years. 2 years after ICI initiation, 39% of patients who discontinued ICI had disease progression, compared with 14% of patients who continued ICI (HR=2.34 (95% CI: 1.07 to 5.12), p=0.034). Among patients who discontinued ICI, those with PR had a numerically higher rate of progression compared with patients with CR at 2 years after ICI discontinuation (56% vs 29%, respectively; HR=1.74 (95% CI: 0.72 to 4.20), p=0.22). Patients who discontinued due to toxicity had numerically higher rates of progression at 2 years (N=28) compared with patients who discontinued electively (N=30) (45% vs 31%, respectively; HR=2.08 (95% CI: 0.79 to 5.46), p=0.14). Among responders who stayed on ICI and had not progressed by 1 year, those who electively discontinued ICI had a high chance of remaining progression-free at 2 years (89%), similar to those who continued ICI (96%, p=0.59).Conclusions This study highlights the high progression risk following ICI discontinuation in advanced MCC, especially among patients with non-CRs or those discontinuing early. While elective discontinuation may be appropriate after durable CRs (response≥1 year), greater caution is warranted in other settings.",
  "authors": [
    {
      "affiliations": [
        "Department of Medicine, Division of Hematology/Oncology, University of Washington, Seattle, Washington, USA",
        "Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA"
      ],
      "name": "Lisa Tachiki"
    },
    {
      "affiliations": [
        "Department of Dermatology, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Yasman Moshiri"
    },
    {
      "affiliations": [
        "Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA"
      ],
      "name": "Daniel S Hippe"
    },
    {
      "affiliations": [
        "Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA"
      ],
      "name": "Emily Gong"
    },
    {
      "affiliations": [
        "Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA"
      ],
      "name": "Lauren Zawacki"
    },
    {
      "affiliations": [
        "Department of Dermatology, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Thomas Pulliam"
    },
    {
      "affiliations": [
        "Department of Dermatology, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Kristina Lachance"
    },
    {
      "affiliations": [
        "Department of Dermatology, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Candice Church"
    },
    {
      "affiliations": [
        "Department of Dermatology, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Alex Fu"
    },
    {
      "affiliations": [
        "Department of Dermatology, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Emily Huynh"
    },
    {
      "affiliations": [
        "Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA",
        "Department of Dermatology, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Allison J Remington"
    },
    {
      "affiliations": [
        "Department of Dermatology, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Nikhil Harikrishnan"
    },
    {
      "affiliations": [
        "Department of Dermatology, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Marika Bierma"
    },
    {
      "affiliations": [
        "Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA"
      ],
      "name": "Coley Doolittle-Amieva"
    },
    {
      "affiliations": [
        "Department of Dermatology, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Tomoko Akaike"
    },
    {
      "affiliations": [
        "Department of Dermatology, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Song Y Park"
    },
    {
      "affiliations": [
        "Department of Dermatology, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Nora A Alexander"
    },
    {
      "affiliations": [
        "Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA"
      ],
      "name": "Lisa Zaba"
    },
    {
      "affiliations": [
        "Department of Medicine, Division of Hematology/Oncology, University of Washington, Seattle, Washington, USA",
        "Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA"
      ],
      "name": "Shailender Bhatia"
    },
    {
      "affiliations": [
        "Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA",
        "Department of Dermatology, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Paul T Nghiem"
    }
  ],
  "title": "Risk of disease progression after discontinuing immunotherapy in 105 patients with Merkel cell carcinoma who responded to PD-1 pathway blockade",
  "uid": "4106030b-4318-544c-9cef-f9ee81f7621b"
}