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. 2015 Oct 1;33(28):3193-8.
doi: 10.1200/JCO.2015.60.8448. Epub 2015 Aug 17.

Immune-Related Adverse Events, Need for Systemic Immunosuppression, and Effects on Survival and Time to Treatment Failure in Patients With Melanoma Treated With Ipilimumab at Memorial Sloan Kettering Cancer Center

Troy Z Horvat  1 , Nelly G Adel  1 , Thu-Oanh Dang  1 , Parisa Momtaz  1 , Michael A Postow  1 , Margaret K Callahan  1 , Richard D Carvajal  1 , Mark A Dickson  1 , Sandra P D'Angelo  1 , Kaitlin M Woo  1 , Katherine S Panageas  1 , Jedd D Wolchok  1 , Paul B Chapman  2
Affiliations

Immune-Related Adverse Events, Need for Systemic Immunosuppression, and Effects on Survival and Time to Treatment Failure in Patients With Melanoma Treated With Ipilimumab at Memorial Sloan Kettering Cancer Center

Troy Z Horvat et al. J Clin Oncol. .

Abstract

Purpose: Ipilimumab is a standard treatment for metastatic melanoma, but immune-related adverse events (irAEs) are common and can be severe. We reviewed our large, contemporary experience with ipilimumab treatment outside of clinical trials to determine the frequency of use of systemic corticosteroid or anti-tumor necrosis factor α (anti-TNFα) therapy and the effect of these therapies on overall survival (OS) and time to treatment failure (TTF).

Patients and methods: We reviewed retrospectively the medical records of patients with melanoma who had received treatment between April 2011 and July 2013 with ipilimumab at the standard dose of 3 mg/kg. We collected data on patient demographics, previous and subsequent treatments, number of ipilimumab doses, irAEs and how they were treated, and overall survival.

Results: Of the 298 patients, 254 (85%) experienced an irAE of any grade. Fifty-six patients (19%) discontinued therapy because of an irAE, most commonly diarrhea. Overall, 103 patients (35%) required systemic corticosteroid treatment for an irAE; 29 (10%) also required anti-TNFα therapy. Defining TTF as either starting a new treatment or death, estimated median TTF was 5.7 months. Twelve percent of patients experienced long-term disease control without receiving additional antimelanoma therapy. OS and TTF were not affected by the occurrence of irAEs or the need for systemic corticosteroids.

Conclusion: IrAEs are common in patients treated with ipilimumab. In our experience, approximately one-third of ipilimumab-treated patients required systemic corticosteroids, and almost one-third of those required further immune suppression with anti-TNFα therapy. Practitioners and patients should be prepared to treat irAEs and should understand that such treatment does not affect OS or TTF.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Incidence of immune-related adverse events (irAEs) by dose of ipilimumab. y-axis indicates the proportion of patients experiencing an irAE of any grade after each of the ipilimumab (Ipi) infusions.
Fig 2.
Fig 2.
Overall survival (OS) and time to treatment failure (TTF) in 298 patients treated with ipilimumab. (A) OS was defined as time from first dose of ipilimumab until death. (B) TTF was defined as time from first dose of ipilimumab until first dose of a subsequent therapy or death, whichever came first. Dashed lines indicate 95% CIs. Black dots represent censored patients.
Fig 3.
Fig 3.
Landmark of correlates of overall survival (OS) and time to treatment failure (TTF) in patients treated with ipilimumab. OS shown after landmark analysis and stratifying by whether patients (A) had immune-related adverse event (irAE) or (B) required systemic corticosteroids. TTF shown after landmark analysis and stratifying by whether patients (C) had irAE or (D) required systemic corticosteroids. Black dots represent censored patients.
See this image and copyright information in PMC

Comment in

  • Reply to A. Indini et al.
    Horvat TZ, Adel NG, Dang TO, Momtaz P, Postow MA, Callahan MK, Carvajal RD, Dickson MA, D'Angelo SP, Woo KM, Panageas KS, Wolchok JD, Chapman PB. Horvat TZ, et al. J Clin Oncol. 2016 Mar 20;34(9):1018-9. doi: 10.1200/JCO.2015.65.7007. Epub 2016 Jan 19. J Clin Oncol. 2016. PMID: 26786917 No abstract available.
  • Immune Suppression and Response to Ipilimumab: Assessing Risk-to-Benefit Ratio.
    Indini A, Di Nicola M, Del Vecchio M, De Braud F. Indini A, et al. J Clin Oncol. 2016 Mar 20;34(9):1017-8. doi: 10.1200/JCO.2015.65.0028. Epub 2016 Jan 19. J Clin Oncol. 2016. PMID: 26786928 No abstract available.

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