CoChat
Sign Up
Cited by 642Cancer Immunotherapy and BiomarkersCutaneous Melanoma Detection and ManagementImmunotherapy and Immune Responses

Ipilimumab Therapy in Patients With Advanced Melanoma and Preexisting Autoimmune Disorders

Johnson, Douglas B., Sullivan, Ryan J., Ott, Patrick A., Carlino, Matteo S., Khushalani, Nikhil I., Ye, Fei, Guminski, Alexander, Puzanov, Igor +13 more·2016·JAMA Oncology
DOI 10.1001/jamaoncol.2015.4368
Open this paper in CoChat — free account

Abstract

IMPORTANCE: Ipilimumab and other immune therapies are effective treatment options for patients with advanced melanoma but cause frequent immune-related toxic effects. Autoimmune diseases are common, and the safety and efficacy of ipilimumab therapy in patients with preexisting autoimmune disorders is not known. OBJECTIVE: To determine the safety and efficacy of ipilimumab therapy in patients with advanced melanoma with preexisting autoimmune disorders. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of patients with advanced melanoma and preexisting autoimmune disorders who received ipilimumab at 9 academic tertiary referral centers from January 1, 2012, through August 1, 2015. The data analysis was performed on August 24, 2015. EXPOSURE: Ipilimumab therapy. MAIN OUTCOMES AND MEASURES: Safety, in terms of frequency of autoimmune flares and conventional immune-related adverse events (irAEs), and efficacy, in terms of response rates and overall survival, were evaluated descriptively. RESULTS: Of the 30 patients who received ipilimumab (17 [57%] male; median [range] age, 59.5 [30-80] y), 6 had rheumatoid arthritis, 5 had psoriasis, 6 had inflammatory bowel disease, 2 had systemic lupus erythematosus, 2 had multiple sclerosis, 2 had autoimmune thyroiditis, and 7 had other conditions. Thirteen patients (43%) were receiving immunosuppressive therapy at the time of initiation of ipilimumab therapy, most commonly low-dose prednisone or hydroxychloroquine. With ipilimumab treatment, 8 patients (27%) experienced exacerbations of their autoimmune condition necessitating systemic treatment; all were managed with corticosteroids. Conventional grade 3 to 5 irAEs occurred in 10 patients (33%) and were reversible with corticosteroids or with infliximab therapy in 2 cases. One patient with baseline psoriasis died of presumed immune-related colitis after a 1-week delay prior to reporting symptoms. Fifteen patients (50%) had neither autoimmune disease flares nor irAEs. Six patients experienced an objective response (20%), including 1 with a durable complete response. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the largest series of patients with preexisting autoimmune disease treated with immune checkpoint inhibitors. Ipilimumab was clinically active and was associated with exacerbations of autoimmune disease and conventional ipilimumab-induced irAEs that were readily manageable with standard therapies when started in a timely fashion. Ipilimumab therapy may be considered in this setting with vigilant clinical monitoring.

Integrity signals

Registry

Crossref · 10.1001/jamaoncol.2015.4368

Cites

30 of 30 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The incidence of endocrine events varies by the type of ICI used.

    “Incidence of endocrine events varies based on type of ICI used (see Figure 2).38”

    From Endocrine toxicities of immune checkpoint inhibitors (2021) · cites this paper as [38]

  • Thyroid events occur in about 10% of patients on anti-PD-1/PD-L1 monotherapy, up to 15-20% on combination PD-1/CTLA-4 blockade, and only 5% on ipilimumab monotherapy.

    “Thyroid events occur in approximately 10% of patients treated with anti-PD-1/PD-L1 monotherapy, and up to 15-20% of those treated with combination PD-1/CTLA-4 blockade (as opposed to only 5% of those treated with ipilimumab monotherapy).9,38”

    From Endocrine toxicities of immune checkpoint inhibitors (2021) · cites this paper as [38]

  • Hypophysitis or hypopituitarism occurs in up to 10% of patients receiving anti-CTLA-4 based therapy, including ipilimumab monotherapy and slightly more commonly combination CTLA-4/PD-1 blockade.

    “hypophysitis or hypopituitarism occurs in up to 10% of patients who receive anti-CTLA-4 based therapy (either with ipilimumab monotherapy, and slightly more commonly with combination CTLA-4/PD-1 blockade).38”

    From Endocrine toxicities of immune checkpoint inhibitors (2021) · cites this paper as [38]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Johnson, D. B., Sullivan, R. J., Ott, P. A., Carlino, M. S., Khushalani, N. I., Ye, F., Guminski, A., Puzanov, I., Lawrence, D. P., Buchbinder, E. I., Mudigonda, T., Spencer, K., Bender, C., Lee, J., Kaufman, H. L., Menzies, A. M., Hassel, J. C., Mehnert, J. M., Sosman, J. A., Long, G. V., & Clark, J. I.
Affiliations
  • Vanderbilt University Medical Center (US)
  • Massachusetts General Hospital (US)
  • Dana-Farber Cancer Institute (US)
  • The University of Sydney (AU)
  • Roswell Park Comprehensive Cancer Center (US)
  • Rutgers Cancer Institute (US)
  • University Hospital Heidelberg (DE)
  • Westmead Hospital (AU)
  • Loyola University Medical Center (US)
Corresponding author
Johnson, Douglas B.
ORCID
Venue
JAMA Oncology
Publisher
American Medical Association (AMA)
Published
2016-02-01
Volume
2
Issue
2
Pages
234
ISSN
2374-2437 (ISSN-L)
DOI
10.1001/jamaoncol.2015.4368
OpenAlex
W2193769500
Cited by
642
References
30
Citations by year
2026: 13 · 2025: 29 · 2024: 49 · 2023: 44 · 2022: 64 · 2021: 73 · 2020: 94 · 2019: 93 · 2018: 65 · 2017: 68 · 2016: 47 · 2013: 1
FWCI
26.20
Type
journal article
Language
en
Open access
closed
Locations
  • JAMA Oncology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (K12 CA 0906525, K12CA090625)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
ipilimumab, advanced melanoma, immune-related adverse events, immune-related colitis, immune-related pneumonitis, immune-related hepatitis, immune-related endocrinopathy, immune-related dermatitis, immune checkpoint inhibitors, immunosuppressive therapy, rheumatoid arthritis, psoriasis, inflammatory bowel disease, systemic lupus erythematosus
MeSH terms
Ipilimumab, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antineoplastic Agents, Autoimmune Diseases, Female, Humans, Male, Melanoma, Middle Aged, Retrospective Studies, Risk Factors, Skin Neoplasms, Time Factors, Autoimmunity, Treatment Outcome, Risk Assessment, Patient Selection, Tertiary Care Centers

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review