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Management Of Immune-related Adverse Events And Kinetics Of Response With Ipilimumab.

J. Weber, K. Kähler, A. Hauschild
Published 2012 · Medicine

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Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152)-ipilimumab and tremelimumab-have been investigated in metastatic melanoma and other cancers and have shown promising results. Recently, ipilimumab was approved by the US Food and Drug Administration for the treatment of metastatic melanoma. We review the literature on managing the adverse effects and kinetics of tumor regression with ipilimumab and provide guidelines on their management. During treatment with these antibodies, a unique set of adverse effects may occur, called immune-related adverse events (irAEs). These include rashes, which may rarely progress to life-threatening toxic epidermal necrolysis, and colitis, characterized by a mild to moderate, but occasionally also severe and persistent diarrhea. Hypophysitis, hepatitis, pancreatitis, iridocyclitis, lymphadenopathy, neuropathies, and nephritis have also been reported with ipilimumab. Early recognition of irAEs and initiation of treatment are critical to reduce the risk of sequelae. Interestingly, irAEs correlated with treatment response in some studies. Unique kinetics of response have been observed with CTLA-4 blockade with at least four patterns: (1) response in baseline lesions by week 12, with no new lesions seen; (2) stable disease, followed by a slow, steady decline in total tumor burden; (3) regression of tumor after initial increase in total tumor burden; and (4) reduction in total tumor burden during or after the appearance of new lesion(s) after week 12. We provide a detailed description of irAEs and recommendations for practicing oncologists who are managing them, along with the unusual kinetics of response associated with ipilimumab therapy.
This paper references
10.1056/NEJMoa1003466
Improved survival with ipilimumab in patients with metastatic melanoma.
F. S. Hodi (2010)
Correlation of clinical and immunological data in a metastatic melanoma patient with heterogeneous tumor responses to ipilimumab therapy.
J. Yuan (2010)
10.1146/ANNUREV.IMMUNOL.23.021704.115611
The B7 family revisited.
R. Greenwald (2005)
10.1200/JCO.2007.25.18_SUPPL.8525
Kinetics of response to ipilimumab (MDX-010) in patients with stage III/IV melanoma
O. Hamid (2007)
10.1097/COC.0b013e318209cda9
Patient Responses to Ipilimumab, a Novel Immunopotentiator for Metastatic Melanoma: How Different are these From Conventional Treatment Responses?
G. Pennock (2012)
10.1158/1078-0432.CCR-09-1024
A Randomized, Double-Blind, Placebo-Controlled, Phase II Study Comparing the Tolerability and Efficacy of Ipilimumab Administered with or without Prophylactic Budesonide in Patients with Unresectable Stage III or IV Melanoma
J. Weber (2009)
10.1097/01.CJI.0000178913.41256.06
Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer.
J. Blansfield (2005)
10.1073/pnas.0830997100
Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients
F. S. Hodi (2003)
10.1016/J.COI.2006.01.011
Principles and use of anti-CTLA4 antibody in human cancer immunotherapy.
K. Peggs (2006)
10.1097/00002371-200411000-00008
Cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma: a new cause of uveitis.
M. Robinson (2004)
10.1016/S1470-2045(09)70334-1
Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study.
J. Wolchok (2010)
10.1158/1078-0432.CCR-11-1823
CTLA-4 Blockade with Ipilimumab: Long-term Follow-up of 177 Patients with Metastatic Melanoma
P. A. Prieto (2012)
10.1200/JCO.2005.06.205
Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4.
P. Attia (2005)
10.1200/JCO.2008.19.2435
Phase I/II trial of tremelimumab in patients with metastatic melanoma.
L. Camacho (2009)
10.1016/1074-7613(95)90125-6
Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4.
E. Tivol (1995)
10.1200/JCO.2005.04.5716
Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4.
Kimberly E. Beck (2006)
10.1200/JCO.2006.24.18_SUPPL.2510
Phase II trial of extended dose anti-CTLA-4 antibody ipilimumab (formerly MDX-010) with a multi-peptide vaccine for resected stages IIIC and IV melanoma.
J. Weber (2006)
10.1200/jco.2009.27.15_suppl.9034
Association between immune-related adverse events (irAEs) and disease control or overall survival in patients (pts) with advanced melanoma treated with 10 mg/kg ipilimumab in three phase II clinical trials.
J. Lutzky (2009)
10.1007/s10620-008-0641-z
Cytotoxic T-Lymphocyte-Associated Antigen 4 Antibody-Induced Colitis and Its Management with Infliximab
R. Johnston (2008)
10.1126/science.270.5238.985
Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4
P. Waterhouse (1995)
10.1073/pnas.1533209100
Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma
G. Phan (2003)
The heterogeneity of the kinetics of response to ipilimumab in metastatic melanoma: patient cases.
Y. Saenger (2008)
10.1200/jco.2009.27.15_suppl.9041
Effect of ipilimumab at 10 mg/kg on disease control in patients (pts) with M1c-stage melanoma in relation to baseline lactate dehydrogenase (LDH) levels.
M. Smylie (2009)
10.1093/annonc/mdq013
Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study.
S. O’Day (2010)
10.1200/JCO.2008.19.8853
Activity of bosutinib, dasatinib, and nilotinib against 18 imatinib-resistant BCR/ABL mutants.
Sara Redaelli (2009)
10.1056/NEJMoa1104621
Ipilimumab plus dacarbazine for previously untreated metastatic melanoma.
C. Robert (2011)
10.1097/CJI.0b013e318193a206
Inflammatory enteric neuropathy with severe constipation after ipilimumab treatment for melanoma: a case report.
S. Bhatia (2009)
10.1053/j.seminoncol.2010.09.015
Development of ipilimumab: contribution to a new paradigm for cancer immunotherapy.
A. Hoos (2010)
10.1007/s00262-008-0642-y
Therapeutic efficacy of ipilimumab, an anti-CTLA-4 monoclonal antibody, in patients with metastatic melanoma unresponsive to prior systemic treatments: clinical and immunological evidence from three patient cases
A. D. Giacomo (2008)
10.1200/JCO.2008.26.15_SUPPL.LBA9011
Phase III, open-label, randomized, comparative study of tremelimumab (CP-675,206) and chemotherapy (temozolomide [TMZ] or dacarbazine [DTIC]) in patients with advanced melanoma
A. Ribas (2008)
10.1158/1078-0432.CCR-09-1624
Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-Related Response Criteria
J. Wolchok (2009)
10.1159/000161122
Anti-CTLA4 Monoclonal Antibody Induced Sarcoidosis in a Metastatic Melanoma Patient
A. Eckert (2008)
10.1158/1078-0432.CCR-07-0187
Prognostic Factors Related to Clinical Response in Patients with Metastatic Melanoma Treated by CTL-Associated Antigen-4 Blockade
Stephanie G Downey (2007)



This paper is referenced by
10.1056/NEJMCPC1302332
Case 21-2013
Ryan J. Sullivan (2013)
10.1111/his.14000
Immune‐related adverse reactions in the hepatobiliary system: second‐generation check‐point inhibitors highlight diverse histological changes
Y. Zen (2019)
10.1038/nrclinonc.2015.152
Cancer-treatment-induced neurotoxicity—focus on newer treatments
Jacqueline B Stone (2016)
10.1007/978-4-431-55031-0_18
Anti-CTLA-4 Ab
T. Tokudome (2016)
10.1093/annonc/mdv623
Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper.
S. Champiat (2016)
10.1097/CCO.0000000000000290
Dermatologic complications of anti-PD-1/PD-L1 immune checkpoint antibodies
V. Sibaud (2016)
10.1007/s10147-017-1108-z
Do all patients in the phase I oncology trials need to be hospitalized? Domestic but outstanding issues for globalization of drug development in Japan
A. Shimomura (2017)
Central nervous system toxicities of anti-cancer immune checkpoint blockade
Jonathan T. Blackmon (2016)
10.13097/archive-ouverte/unige:113401
Hypophysite induite par les anticorps monoclonaux anti-CTLA-4
Jaafar Jaafar (2019)
Expert opinion on pituitary complications in immunotherapy Opinion d ’ expert sur les complications hypophysaires de l ’ immunothérapie
Claire Brieta (2018)
10.1007/s11901-017-0381-7
Hepatotoxicity of New Antitumor Agents
Nelia Hernández (2017)
10.1001/jamaoncol.2018.5860
Profiling Preexisting Antibodies in Patients Treated With Anti–PD-1 Therapy for Advanced Non–Small Cell Lung Cancer
Yukihiro Toi (2018)
10.2217/mmt-2017-0015
Management of the cutaneous adverse effects of antimelanoma therapy.
R. Liu (2017)
10.4137/CMED.S22469
Immune Checkpoint Inhibitor Therapy Associated Hypophysitis
Moeber Mahzari (2015)
10.1158/2326-6066.CIR-14-0217
Survivorship in Immune Therapy: Assessing Chronic Immune Toxicities, Health Outcomes, and Functional Status among Long-term Ipilimumab Survivors at a Single Referral Center
D. Johnson (2015)
10.1016/j.lungcan.2015.02.007
Optimal management of immune-related toxicities associated with checkpoint inhibitors in lung cancer.
M. Howell (2015)
10.1111/ajco.13332
The role of immunosuppressive agents in the management of severe and refractory immune‐related adverse events
A. Wang (2020)
10.1136/bcr-2019-233519
CMV coinfection in treatment refractory immune checkpoint inhibitor colitis
Kevin B Harris (2020)
10.1136/jitc-2020-000648
Current challenges for assessing the long-term clinical benefit of cancer immunotherapy: a multi-stakeholder perspective
C. Quinn (2020)
10.1007/s00595-020-02048-w
Systemic inflammatory response and nutritional biomarkers as predictors of nivolumab efficacy for gastric cancer
T. Namikawa (2020)
10.1186/s12902-019-0335-x
Late-onset isolated adrenocorticotropic hormone deficiency caused by nivolumab: a case report
A. Takeno (2019)
Foreign body reaction triggered by CTLA-4 blockade 25 years after dermal filler injection , a case report
C. Bisschop ()
10.1146/annurev-med-092012-112807
Immune modulation in cancer with antibodies.
D. Page (2014)
Noninvasive Imaging of Cancer Immunotherapy
Omar Abousaway (2020)
10.1158/1078-0432.CCR-15-1136
Nivolumab in Resected and Unresectable Metastatic Melanoma: Characteristics of Immune-Related Adverse Events and Association with Outcomes
Morganna Freeman-Keller (2015)
10.1016/J.ANNDER.2013.01.442
Anomalies pigmentaires induites par les traitements anticancéreux. Deuxième partie : les thérapies ciblées
V. Sibaud (2013)
10.1007/978-3-030-04489-3
Clinical Ophthalmic Oncology
A. Singh (2019)
Kinetics of Appearance of Immune-Related Adverse Events
M. Postow (2015)
10.14694/EDBK_159084
Current State of Immune-Based Therapies for Glioblastoma.
M. Lim (2016)
Ipilimumab-associated halo-like inflammatory reactions around nevi during therapy for metastatic melanoma.
Dema T. Alniemi (2018)
10.1158/1078-0432.CCR-15-2569
Molecular Pathways: Immune Checkpoint Antibodies and their Toxicities
S. Cousin (2016)
10.3390/cancers12082314
Endocrine Adverse Events of Nivolumab in Non-Small Cell Lung Cancer Patients—Literature Review
M. Dudzińska (2020)
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