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.
OBJECTIVE
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).


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.


CONCLUSIONS
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.
Troy Z. Horvat, Nelly G. Adel, Thu-Oanh Dang, Kaitlin M. Woo, Katherine S. Panageas, Parisa Momtaz, Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Memorial Sloan Kettering Cancer Center; Jedd D. Wolchok, Ludwig Institute for Cancer Research; and Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Weill Cornell Medical College, New York, NY.
Troy Z
TZ
Horvat
Troy Z. Horvat, Nelly G. Adel, Thu-Oanh Dang, Kaitlin M. Woo, Katherine S. Panageas, Parisa Momtaz, Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Memorial Sloan Kettering Cancer Center; Jedd D. Wolchok, Ludwig Institute for Cancer Research; and Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Weill Cornell Medical College, New York, NY.
Nelly G
NG
Adel
Troy Z. Horvat, Nelly G. Adel, Thu-Oanh Dang, Kaitlin M. Woo, Katherine S. Panageas, Parisa Momtaz, Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Memorial Sloan Kettering Cancer Center; Jedd D. Wolchok, Ludwig Institute for Cancer Research; and Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Weill Cornell Medical College, New York, NY.
Thu-Oanh
TO
Dang
Troy Z. Horvat, Nelly G. Adel, Thu-Oanh Dang, Kaitlin M. Woo, Katherine S. Panageas, Parisa Momtaz, Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Memorial Sloan Kettering Cancer Center; Jedd D. Wolchok, Ludwig Institute for Cancer Research; and Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Weill Cornell Medical College, New York, NY.
Parisa
P
Momtaz
Troy Z. Horvat, Nelly G. Adel, Thu-Oanh Dang, Kaitlin M. Woo, Katherine S. Panageas, Parisa Momtaz, Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Memorial Sloan Kettering Cancer Center; Jedd D. Wolchok, Ludwig Institute for Cancer Research; and Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Weill Cornell Medical College, New York, NY.
Michael A
MA
Postow
Troy Z. Horvat, Nelly G. Adel, Thu-Oanh Dang, Kaitlin M. Woo, Katherine S. Panageas, Parisa Momtaz, Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Memorial Sloan Kettering Cancer Center; Jedd D. Wolchok, Ludwig Institute for Cancer Research; and Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Weill Cornell Medical College, New York, NY.
Margaret K
MK
Callahan
Troy Z. Horvat, Nelly G. Adel, Thu-Oanh Dang, Kaitlin M. Woo, Katherine S. Panageas, Parisa Momtaz, Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Memorial Sloan Kettering Cancer Center; Jedd D. Wolchok, Ludwig Institute for Cancer Research; and Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Weill Cornell Medical College, New York, NY.
Richard D
RD
Carvajal
Troy Z. Horvat, Nelly G. Adel, Thu-Oanh Dang, Kaitlin M. Woo, Katherine S. Panageas, Parisa Momtaz, Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Memorial Sloan Kettering Cancer Center; Jedd D. Wolchok, Ludwig Institute for Cancer Research; and Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Weill Cornell Medical College, New York, NY.
Mark A
MA
Dickson
Troy Z. Horvat, Nelly G. Adel, Thu-Oanh Dang, Kaitlin M. Woo, Katherine S. Panageas, Parisa Momtaz, Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Memorial Sloan Kettering Cancer Center; Jedd D. Wolchok, Ludwig Institute for Cancer Research; and Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Weill Cornell Medical College, New York, NY.
Sandra P
SP
D'Angelo
Troy Z. Horvat, Nelly G. Adel, Thu-Oanh Dang, Kaitlin M. Woo, Katherine S. Panageas, Parisa Momtaz, Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Memorial Sloan Kettering Cancer Center; Jedd D. Wolchok, Ludwig Institute for Cancer Research; and Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Weill Cornell Medical College, New York, NY.
Kaitlin M
KM
Woo
Troy Z. Horvat, Nelly G. Adel, Thu-Oanh Dang, Kaitlin M. Woo, Katherine S. Panageas, Parisa Momtaz, Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Memorial Sloan Kettering Cancer Center; Jedd D. Wolchok, Ludwig Institute for Cancer Research; and Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Weill Cornell Medical College, New York, NY.
Katherine S
KS
Panageas
Troy Z. Horvat, Nelly G. Adel, Thu-Oanh Dang, Kaitlin M. Woo, Katherine S. Panageas, Parisa Momtaz, Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Memorial Sloan Kettering Cancer Center; Jedd D. Wolchok, Ludwig Institute for Cancer Research; and Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Weill Cornell Medical College, New York, NY.
Jedd D
JD
Wolchok
Troy Z. Horvat, Nelly G. Adel, Thu-Oanh Dang, Kaitlin M. Woo, Katherine S. Panageas, Parisa Momtaz, Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Memorial Sloan Kettering Cancer Center; Jedd D. Wolchok, Ludwig Institute for Cancer Research; and Michael A. Postow, Margaret K. Callahan, Richard D. Carvajal, Mark A. Dickson, Sandra P. D'Angelo, Jedd D. Wolchok, and Paul B. Chapman, Weill Cornell Medical College, New York, NY. chapmanp@mskcc.org.
Paul B
PB
Chapman
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D018572:Disease-Free Survival; D057915:Drug Substitution; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D008297:Male; D008499:Medical Records; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D009519:New York City; D012189:Retrospective Studies; D012307:Risk Factors; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D000074324:Ipilimumab; D014409:Tumor Necrosis Factor-alpha