Effectiveness and Tolerability of Ipilimumab: Experiences From 198 Patients Included in a Named-Patient Program in Various Daily-Practice Settings and Multiple Institutions
Abstract
BACKGROUND: Ipilimumab is an approved anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody introducing immune responses in melanoma patients. Treatment experiences from named-patient programs support the evaluation of the efficacy and tolerability of new medicines under usual circumstances of health care practice. Here, the largest ever reported cohort treated with ipilimumab 3 mg/kg alone is described. METHODS: This report retrospectively analyzes data of 198 patients who were followed up in 15 hospital centers in Germany between April 2010 and March 2013. Patients had received prior therapy for unresectable stage III or IV melanoma before receiving ipilimumab (4 doses of 3 mg/kg every 21 d). Routine staging and tumor response evaluation procedures were applied. RESULTS: Of the patients, 119 received the planned 4-course therapy schedule; in further 79 patients, the number of doses was reduced mainly because of toxicity or fast progression. In all, 196 patients were eligible for evaluation of the efficacy of ipilimumab under routine care conditions. Median overall survival (OS) was 6.8 months [95% confidence interval, 5.6-10.3] from the start of therapy. OS differed significantly among patients who received 4 doses (n=119) and those receiving <4 doses (n=79) (14.2 vs. 2.0 mo; P<0.0001). The overall response rate (ORR) of 11% was in the same range as reported from previous clinical trials; and stable disease (SD) was observed in 11% resulting in a disease control rate (ORR+SD) of 22%. In 23 of the 79 patients with reduced dosing, dose omission was most probably caused by toxicity, whereas 56 patients had progressive disease before receiving all 4 treatment cycles. Immune-related adverse events (irAE) were reported in 30% of all treated patients, the occurrence of irAE correlated significantly with the probability of response to therapy and prolonged OS. CONCLUSION: In this named-patient program including heavily pretreated patients, the efficacy and tolerability of ipilimumab 3 mg/kg corresponds with findings from the confirmatory clinical trial.
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In patients treated with anti-CTLA-4 antibodies, the association between IRAEs and ICI efficacy has been less uniform.
“In patients treated with anti-CTLA-4 antibodies, this association has been less uniform [21–25].”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [21]
In that analysis, among responding patients, a higher proportion experienced any grade IRAEs compared to no IRAEs (p = .04).
“Among responding patients, a higher proportion experienced any grade IRAEs compared to no IRAEs (p = .04).”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [21]
In a retrospective analysis of 198 metastatic pretreated melanoma patients who received ipilimumab, 29.8% experienced IRAEs.
“In a retrospective analysis of 198 metastatic pre-treated melanoma patients who received ipilimumab 3 mg/kg every 3 weeks for 4 doses, 29.8% experienced IRAEs [21].”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [21]
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Background
- Authors
- Eigentler, T. K., Schlaak, M., Hassel, J. C., Loquai, C., Stoffels, I., Gutzmer, R., Pätzold, S., Mohr, P., Keller, U., Starz, H., Ulrich, J., Tsianakas, A., Kähler, K., Hauschild, A., Janssen, E., Schuler-Thurner, B., Weide, B., & Garbe, C.
- Affiliations
- University of Cologne (DE)
- University Hospital Cologne (DE)
- University Hospital Heidelberg (DE)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- University of Duisburg-Essen (DE)
- Medizinische Hochschule Hannover (DE)
- University Hospital Frankfurt (DE)
- Universitätsklinikum Tübingen (DE)
- University Hospital Augsburg (DE)
- University Hospital Münster (DE)
- Universitätsklinikum des Saarlandes (DE)
- Corresponding author
- Eigentler, Thomas K.
- Mohr, Peter
- Weide, Benjamin
- Garbe, Claus
- ORCID
- Venue
- Journal of Immunotherapy
- Published
- 2014-09
- Volume
- 37
- Issue
- 7
- Pages
- 374-381
- ISSN
- 1524-9557 (ISSN-L)
- OpenAlex
- W2312943839
- Cited by
- 23
- References
- 0
- Citations by year
- 2024: 2 · 2022: 1 · 2020: 5 · 2019: 3 · 2017: 5 · 2016: 3 · 2015: 4
- FWCI
- 1.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Immunotherapy (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- 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, melanoma, CTLA-4 blockade, immune checkpoint inhibitors, overall survival, immune-related adverse events, treatment efficacy, tolerability, dose reduction, real-world effectiveness, named patient program, disease control rate
- MeSH terms
- Ipilimumab, Antibodies, Monoclonal, Antineoplastic Agents, Female, Follow-Up Studies, Humans, Male, Melanoma, Neoplasm Metastasis, Neoplasm Staging, Retrospective Studies, Treatment Outcome
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