Management of Immune-Related Adverse Events and Kinetics of Response With Ipilimumab

Weber, Jeffrey S.; Kähler, Katharina C.; Hauschild, Axel

doi:10.1200/jco.2012.41.6750

Cited by 1,415Cancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesCutaneous Melanoma Detection and Management

Management of Immune-Related Adverse Events and Kinetics of Response With Ipilimumab

Weber, Jeffrey S., Kähler, Katharina C., Hauschild, Axel·2012·Journal of Clinical Oncology

DOI 10.1200/jco.2012.41.6750

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Abstract

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.

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Fundamental Mechanisms of Regulated Cell Death and Implications for Heart Disease
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Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper
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“ICBs generate atypical types of tumor responses [15] and have a specific toxicity profile which is challenging the historical oncologists’ practices [16].”
Background
Nivolumab in Resected and Unresectable Metastatic Melanoma: Characteristics of Immune-Related Adverse Events and Association with Outcomes
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Self-citation
Immune checkpoint inhibition for hypermutant glioblastoma multiforme resulting from germline biallelic mismatch repair deficiency
Bouffet, E., Larouche, V., Campbell, B. B., Merico, D., de Borja, R., Aronson, M., Durno, C., Krueger, J., Cabric, V., Ramaswamy, V., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.66.6552 · Cited by 857 · see citing works
Management of toxicities of immune checkpoint inhibitors
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“the first few weeks on treatment whereas diarrhea and colitis tend to occur between weeks 5 and 10, liver toxicity from week 7 to 14 and hypophysitis after 6 weeks.[28] Most ipilimumab-related irAEs occur during the induction period.”
BackgroundInfluential
Society for immunotherapy of cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events
Brahmer, J. R., Abu-Sbeih, H., Ascierto, P. A., Brufsky, J., Cappelli, L. C., Cortazar, F. B., Gerber, D. E., Hamad, L., Hansen, E., Johnson, D. B., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-002435 · Cited by 917 · see citing works
Treatment of the Immune-Related Adverse Effects of Immune Checkpoint Inhibitors
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Randomized, double-blind, phase III trial of ipilimumab versus placebo in asymptomatic or minimally symptomatic patients with metastatic chemotherapy-naive castration-resistant prostate cancer
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Incidence of Programmed Cell Death 1 Inhibitor–Related Pneumonitis in Patients With Advanced Cancer
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Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody
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Cancer immunotherapy—immune checkpoint blockade and associated endocrinopathies.
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Toxicities of Immunotherapy for the Practitioner
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Self-citation
Ipilimumab Therapy in Patients With Advanced Melanoma and Preexisting Autoimmune Disorders
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., et al. (2016) · JAMA Oncology · doi:10.1001/jamaoncol.2015.4368 · Cited by 642 · see citing works
Evolving synergistic combinations of targeted immunotherapies to combat cancer
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Dermatologic Reactions to Immune Checkpoint Inhibitors
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“immune checkpoint inhibitors [2, 4, 5, 7, 11], and this does not appear to be dose dependent [10, 20, 21].”
Background
Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy
Tang, T., Huang, X., Zhang, G., Hong, Z., Bai, X., & Liang, T. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00449-4 · Cited by 613 · see citing works
Resistance to PD1/PDL1 checkpoint inhibition
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Management of Immunotherapy-Related Toxicities, Version 1.2019, NCCN Clinical Practice Guidelines in Oncology
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Development of immuno-oncology drugs — from CTLA4 to PD1 to the next generations
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In situ activation of platelets with checkpoint inhibitors for post-surgical cancer immunotherapy
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Immune Modulation in Cancer with Antibodies
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New drugs, new toxicities: severe side effects of modern targeted and immunotherapy of cancer and their management
on behalf of the Intensive Care in Hematological and Oncological Patients (iCHOP) Collaborative Group, Kroschinsky, F., Stölzel, F., von Bonin, S., Beutel, G., Kochanek, M., Kiehl, M. G., & Schellongowski, P. (2017) · Critical Care · doi:10.1186/s13054-017-1678-1 · Cited by 505 · see citing works
“Symptoms appear, on average, after 9 weeks of treatment [18].”
BackgroundInfluential
Dexamethasone-induced immunosuppression: mechanisms and implications for immunotherapy
Giles, A. J., Hutchinson, M.-K. N. D., Sonnemann, H. M., Jung, J., Fecci, P. E., Ratnam, N. M., Zhang, W., Song, H., Bailey, R., Davis, D. L., et al. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0371-5 · Cited by 498 · see citing works
“Corticosteroids are also first-line agents against immune-related adverse events (irAEs) that may develop during or following immunotherapy, particularly checkpoint blockade [6, 7].”
Background
Comprehensive Meta-analysis of Key Immune-Related Adverse Events from CTLA-4 and PD-1/PD-L1 Inhibitors in Cancer Patients
de Velasco, G., Je, Y., Bossé, D., Awad, M. M., Ott, P. A., Moreira, R. B., Schutz, F. A. B., Joaquim Bellmunt, B., Sonpavde, G., Hodi, F. S., et al. (2017) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-16-0237 · Cited by 491 · see citing works
Ipilimumab-Induced Hypophysitis: A Detailed Longitudinal Analysis in a Large Cohort of Patients With Metastatic Melanoma
Faje, A. T., Sullivan, R. J., Lawrence, D. P., Tritos, N. A., Fadden, R. M., Klibanski, A., & Nachtigall, L. B. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-2306 · Cited by 482 · see citing works
Immune checkpoint inhibitor–related dermatologic adverse events
Geisler, A. N., Phillips, G. S., M.S, D. M. B., Wu, J., Leung, D. Y. M., Moy, A. P., Kern, J. A., & Lacouture, M. E. (2020) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2020.03.132 · Cited by 490 · see citing works
Phase II Study of the MEK1/MEK2 Inhibitor Trametinib in Patients With Metastatic BRAF -Mutant Cutaneous Melanoma Previously Treated With or Without a BRAF Inhibitor
Kim, K. B., Kefford, R. F., Pavlick, A. C., Infante, J. R., Ribas, A., Sosman, J. A., Fecher, L. A., Millward, M., McArthur, G. A., Hwu, P., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2012.43.5966 · Cited by 475 · see citing works
Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1
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The Price of Tumor Control: An Analysis of Rare Side Effects of Anti-CTLA-4 Therapy in Metastatic Melanoma from the Ipilimumab Network
Voskens, C., Goldinger, S. M., Loquai, C., Robert, C., Kaehler, K. C., Berking, C., Bergmann, T., Bockmeyer, C. L., Eigentler, T., Fluck, M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053745 · Cited by 463 · see citing works
Self-citation
Recent Advances in Hyperthermia Therapy‐Based Synergistic Immunotherapy
Chang, M., Hou, Z., Wang, M., Li, C., & Lin, J. (2020) · Advanced Materials · doi:10.1002/adma.202004788 · Cited by 452 · see citing works
Patterns of onset and resolution of immune‐related adverse events of special interest with ipilimumab
Weber, J. S., Dummer, R., de Pril, V., Lebbé, C., Hodi, F. S., & for the MDX010‐20 Investigators (2013) · Cancer · doi:10.1002/cncr.27969 · Cited by 447 · see citing works
Self-citation
Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study
Kelley, R. K., Sangro, B., Harris, W. P., Ikeda, M., Okusaka, T., Kang, Y., Qin, S., Tai, D. W.-M., Lim, H. Y., Yau, T. C. C., et al. (2021) · Journal of Clinical Oncology · doi:10.1200/jco.20.03555 · Cited by 450 · see citing works
“incorporating higher doses of anti-CTLA-4 improved efficacy but were also associated with increased anti-CTLA-4 dose-dependent toxicity.(7-11) Collective evidence indicates that prolonged or multiple exposures to CTLA-4 inhibitors may not be required for effective antitumor responses.”
Background
Is autoimmunity the Achilles' heel of cancer immunotherapy?
June, C. H., Warshauer, J. T., & Bluestone, J. A. (2017) · Nature Medicine · doi:10.1038/nm.4321 · Cited by 445 · see citing works
Adverse Events Associated with Immune Checkpoint Blockade in Patients with Cancer: A Systematic Review of Case Reports
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“The most common irAEs in data pooled from clinical trials include hypophysitis, colitis, hepatitis, pneumonitis, and rash [16].”
Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial
Maio, M., Scherpereel, A., Calabrò, L., Aerts, J. G. J. V., Cedrés, S., Bearz, A., Nackaerts, K., Fennell, D. A., Kowalski, D. M., Tsao, A. S., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30446-1 · Cited by 422 · see citing works
Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor
Belum, V. R., Benhuri, B., Postow, M. A., Hellmann, M. D., Lesokhin, A. M., Segal, N. H., Motzer, R. J., Wu, S., Busam, K. J., Wolchok, J. D., et al. (2016) · European Journal of Cancer · doi:10.1016/j.ejca.2016.02.010 · Cited by 418 · see citing works
Endocrine Side Effects Induced by Immune Checkpoint Inhibitors
Corsello, S. M., Barnabei, A., Marchetti, P., De Vecchis, L., Salvatori, R., & Torino, F. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-4075 · Cited by 403 · see citing works
Immune checkpoint inhibitors in clinical practice: update on management of immune-related toxicities.
Villadolid, J. J., & Amin, A. (2015) · PubMed Central · doi:10.3978/j.issn.2218-6751.2015.06.06 · Cited by 413 · see citing works
Managing Immune Checkpoint-Blocking Antibody Side Effects
Postow, M. A. (2015) · American Society of Clinical Oncology Educational Book · doi:10.14694/edbook_am.2015.35.76 · Cited by 401 · see citing works
Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy
Eigentler, T., Hassel, J. C., Berking, C., Aberle, J., Bachmann, O. P., Grünwald, V., Kähler, K. C., Loquai, C., Reinmuth, N., Steins, M. B., et al. (2016) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.02.003 · Cited by 405 · see citing works
“In refractory cases, therapy must be permanently discontinued [33], and immunosuppressive treatment should be escalated.”
BackgroundSelf-citation
Rheumatic and Musculoskeletal Immune‐Related Adverse Events Due to Immune Checkpoint Inhibitors: A Systematic Review of the Literature
Cappelli, L. C., Gutierrez, A. K., Bingham, C. O., & Shah, A. A. (2016) · Arthritis Care & Research · doi:10.1002/acr.23177 · Cited by 404 · see citing works
Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab
Cappelli, L. C., Gutierrez, A. K., Baer, A. N., Albayda, J., Manno, R., Haque, U. J., Lipson, E. J., Bleich, K. B., Shah, A. A., Naidoo, J., et al. (2016) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2016-209595 · Cited by 397 · see citing works
A cancer vaccine-mediated postoperative immunotherapy for recurrent and metastatic tumors
Wang, T., Wang, D., Yu, H., Feng, B., Zhou, F., Zhang, H., Zhou, L., Jiao, S., & Li, Y. (2018) · Nature Communications · doi:10.1038/s41467-018-03915-4 · Cited by 394 · see citing works
Circulating Cytokines Predict Immune-Related Toxicity in Melanoma Patients Receiving Anti-PD-1–Based Immunotherapy
Lim, S. Y., Lee, J. H., Gide, T. N., Menzies, A. M., Guminski, A., Carlino, M. S., Breen, E. J., Yang, J. Y. H., Ghazanfar, S., Kefford, R. F., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-2795 · Cited by 381 · see citing works
“events (irAEs, reviewed in (9)), despite grade III/IV irAEs occurring in over 50% of patients 14 treated with combination immune checkpoint inhibitors (10, 11).”
Background
Lessons learned from the blockade of immune checkpoints in cancer immunotherapy
Li, X., Shao, C., Shi, Y., & Han, W. (2018) · Journal of Hematology & Oncology · doi:10.1186/s13045-018-0578-4 · Cited by 385 · see citing works
Interleukin-6 blockade abrogates immunotherapy toxicity and promotes tumor immunity
Hailemichael, Y., Johnson, D. H., Abdel‐Wahab, N., Foo, W. C., Bentebibel, S.-E., Daher, M., Haymaker, C., Wani, K., Saberian, C., Ogata, D., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.04.004 · Cited by 365 · see citing works
Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial
Calabrò, L., Morra, A., Fonsatti, E., Cutaia, O., Amato, G., Giannarelli, D., Giacomo, A. M. D., Danielli, R., Altomonte, M., Mutti, L., et al. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70381-4 · Cited by 353 · see citing works
Clinical Pharmacokinetics and Pharmacodynamics of Immune Checkpoint Inhibitors
Centanni, M., Moes, D. J. A. R., Trocóniz, I. F., Ciccolini, J., & van Hasselt, J. G. C. (2019) · Clinical Pharmacokinetics · doi:10.1007/s40262-019-00748-2 · Cited by 358 · see citing works
Profiling Preexisting Antibodies in Patients Treated With Anti–PD-1 Therapy for Advanced Non–Small Cell Lung Cancer
Toi, Y., Sugawara, S., Sugisaka, J., Ono, H., Kawashima, Y., Aiba, T., Kawana, S., Saito, R., Aso, M., Tsurumi, K., et al. (2019) · JAMA Oncology · doi:10.1001/jamaoncol.2018.5860 · Cited by 352 · see citing works
Cancer Immunotherapy with Anti-CTLA-4 Monoclonal Antibodies Induces an Inflammatory Bowel Disease
Marthey, L., Mateus, C., Mussini, C., Nachury, M., Nancey, S., Grange, F., Zallot, C., Peyrin‐Biroulet, L., Rahier, J., de Beauregard, M. B., et al. (2016) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjv227 · Cited by 341 · see citing works
CHECKPOINT INHIBITOR IMMUNE THERAPY: Systemic Indications and Ophthalmic Side Effects
Dalvin, L. A., Shields, C. L., Orloff, M., Sato, T., & Shields, J. A. (2018) · Retina · doi:10.1097/iae.0000000000002181 · Cited by 336 · see citing works
Safety and Efficacy of Re-treating with Immunotherapy after Immune-Related Adverse Events in Patients with NSCLC
Santini, F. C., Rizvi, H., Plodkowski, A. J., Ni, A., Lacouture, M. E., Gambarin-Gelwan, M., Wilkins, O., Panora, E., Halpenny, D. F., Long, N. M., et al. (2018) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-17-0755 · Cited by 331 · see citing works
Combined immune checkpoint blockade (anti-PD-1/anti-CTLA-4): Evaluation and management of adverse drug reactions
Hassel, J. C., Heinzerling, L., Aberle, J., Bähr, O., Eigentler, T., Grimm, M., Grünwald, V., Leipe, J., Reinmuth, N., Tietze, J. K., et al. (2017) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2017.05.003 · Cited by 331 · see citing works
Immunotherapy and hypophysitis: clinical presentation, treatment, and biologic insights
Faje, A. (2016) · Pituitary · doi:10.1007/s11102-015-0671-4 · Cited by 326 · see citing works
“pletion of Ipi therapy with or without temporary interruption may be safely tolerated in some patients with less severe cases of hypophysitis [16, 17, 54].”
Background
Experience in daily practice with ipilimumab for the treatment of patients with metastatic melanoma: an early increase in lymphocyte and eosinophil counts is associated with improved survival
Delyon, J., Mateus, C., Lefeuvre, D., Lanoy, E., Zitvogel, L., Chaput, N., Roy, S., Eggermont, A. M. M., Routier, E., & Robert, C. (2013) · Annals of Oncology · doi:10.1093/annonc/mdt027 · Cited by 318 · see citing works
Phase II Study of Autologous Monocyte-Derived mRNA Electroporated Dendritic Cells (TriMixDC-MEL) Plus Ipilimumab in Patients With Pretreated Advanced Melanoma
Wilgenhof, S., Corthals, J., Heirman, C., van Baren, N., Lucas, S., Kvistborg, P., Thielemans, K., & Neyns, B. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.63.4121 · Cited by 312 · see citing works
“All immune-related AEs were managed using established treatment algorithms.(25) Grade 1 to 2 dermatitis (diffuse itching, erythema) was the most frequent AE and was reported by 64% of patients.”
Method
Mechanisms and therapeutic potentials of cancer immunotherapy in combination with radiotherapy and/or chemotherapy
Yu, W., Sun, G., Li, J., Jiang, X., & Wang, X. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.02.048 · Cited by 309 · see citing works
Development of ipilimumab: a novel immunotherapeutic approach for the treatment of advanced melanoma
Wolchok, J. D., Hodi, F. S., Weber, J. S., Allison, J. P., Urba, W. J., Robert, C., O'Day, S. J., Hoos, A., Humphrey, R. W., Berman, D. M., et al. (2013) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12180 · Cited by 302 · see citing works
Self-citation
Association of Immune-Related Adverse Events with Clinical Benefit in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Nivolumab
Toi, Y., Sugawara, S., Kawashima, Y., Aiba, T., Kawana, S., Saito, R., Tsurumi, K., Suzuki, K., Shimizu, H., Sugisaka, J., et al. (2018) · The Oncologist · doi:10.1634/theoncologist.2017-0384 · Cited by 294 · see citing works
“However, T-cell activation can cause immune-related adverse events (irAEs), such as skin reactions, thyroid dysfunction, pneumonitis, and hepatitis, that do not occur with conventional cytotoxic anticancer agents [9], indicating the need for a different approach in managing adverse events from nivolumab.”
Background
Immune-related toxicities of checkpoint inhibitors: mechanisms and mitigation strategies
Sullivan, R. J., & Weber, J. S. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00259-5 · Cited by 303 · see citing works
Self-citation
The Spectrum of Serious Infections Among Patients Receiving Immune Checkpoint Blockade for the Treatment of Melanoma
Castillo, M. D., Romero, F. A. R., Argüello, E., Kyi, C., Postow, M. A., & Redelman‐Sidi, G. (2016) · Clinical Infectious Diseases · doi:10.1093/cid/ciw539 · Cited by 292 · see citing works
“These toxicities affect a variety of organ systems including skin (rash), gastrointestinal tract (colitis), pancreas (pancreatitis), liver (hepatitis), endocrine (hypophysitis, thyroiditis), lung (pneumonitis), and kidneys (nephritis) [11, 12].”
Background
Endocrine-related adverse events associated with immune checkpoint blockade and expert insights on their management
Sznol, M., Postow, M. A., Davies, M. J., Pavlick, A. C., Plimack, E. R., Shaheen, M. F., Veloski, C., & Robert, C. (2017) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2017.06.002 · Cited by 290 · see citing works
Pooled Analysis Safety Profile of Nivolumab and Ipilimumab Combination Therapy in Patients With Advanced Melanoma
Sznol, M., Ferrucci, P. F., Hogg, D., Atkins, M. B., Wolter, P., Guidoboni, M., Lebbé, C., Kirkwood, J. M., Schachter, J., Daniels, G. A., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.72.1167 · Cited by 289 · see citing works
Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma
Liao, B., Shroff, S., Kamiya-Matsuoka, C., & Tummala, S. (2014) · Neuro-Oncology · doi:10.1093/neuonc/nou001 · Cited by 288 · see citing works
Hepatotoxicity of immune checkpoint inhibitors: a histology study of seven cases in comparison with autoimmune hepatitis and idiosyncratic drug-induced liver injury
Zen, Y., & Yeh, M. M. (2018) · Modern Pathology · doi:10.1038/s41379-018-0013-y · Cited by 289 · see citing works
“Therefore, the side effects of checkpoint inhibitors are often referred to as “immune-mediated adverse events” in order to distinguish them from usual idiosyncratic drug-induced organ damage [16].”
Background
Long-term follow-up of ipilimumab-induced hypophysitis, a common adverse event of the anti-CTLA-4 antibody in melanoma
Albarel, F., Gaudy‐Marqueste, C., Castinetti, F., Carré, T., Morange, I., Conte‐Devolx, B., Grob, J., & Brue, T. C. (2014) · European Journal of Endocrinology · doi:10.1530/eje-14-0845 · Cited by 286 · see citing works
Adverse Events Following Cancer Immunotherapy: Obstacles and Opportunities
Pauken, K. E., Dougan, M., Rose, N. R., Lichtman, A. H., & Sharpe, A. H. (2019) · Trends in Immunology · doi:10.1016/j.it.2019.04.002 · Cited by 280 · see citing works
Immunotherapy in melanoma: Recent advances and future directions
Franklin, C., Livingstone, E., Roesch, A., Schilling, B., & Schadendorf, D. (2016) · European Journal of Surgical Oncology · doi:10.1016/j.ejso.2016.07.145 · Cited by 277 · see citing works
Cancer-treatment-induced neurotoxicity—focus on newer treatments
Stone, J. B., & DeAngelis, L. M. (2015) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.152 · Cited by 276 · see citing works
Systemic High-Dose Corticosteroid Treatment Does Not Improve the Outcome of Ipilimumab-Related Hypophysitis: A Retrospective Cohort Study
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Systematic review: colitis associated with anti‐ CTLA ‐4 therapy
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Review Article Immune-Mediated Adverse Events Associated with Ipilimumab CTLA-4 Blockade Therapy: The Underlying Mechanisms and Clinical Management
Tarhini, A. A. (2013)

Authors: Weber, J. S., Kähler, K. C., & Hauschild, A.
Affiliations: Moffitt Cancer Center (US)
ORCID: Weber, Jeffrey S.
Kähler, Katharina C.
Hauschild, Axel
Venue: Journal of Clinical Oncology
Publisher: American Society of Clinical Oncology (ASCO)
Published: 2012-07-20
Volume: 30
Issue: 21
Pages: 2691-2697
ISSN: 0732-183X (ISSN-L)
1527-7755
DOI: 10.1200/jco.2012.41.6750
OpenAlex: W2109653150
Cited by: 1,415
References: 33
Citations by year: 2026: 24 · 2025: 35 · 2024: 59 · 2023: 79 · 2022: 84 · 2021: 117 · 2020: 129 · 2019: 123 · 2018: 146 · 2017: 153 · 2016: 152 · 2015: 145 · 2014: 94 · 2013: 65 · 2012: 9
FWCI: 10.34
Type: journal article
Language: en
Open access: closed
Locations: Journal of Clinical Oncology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
Keywords: ipilimumab, immune-related adverse events, CTLA-4 blockade, metastatic melanoma, immune checkpoint inhibitors, toxic epidermal necrolysis, colitis, hypophysitis, hepatitis, iridocyclitis, neuropathy, nephritis, adverse event management
MeSH terms: Ipilimumab, Antibodies, Monoclonal, Antineoplastic Agents, Colitis, Drug Eruptions, Diarrhea, Humans, Liver, Lymphatic Diseases, Melanoma, Mucous Membrane, Pancreatitis, Peripheral Nervous System Diseases, Pituitary Gland, Skin, Skin Neoplasms, Stevens-Johnson Syndrome, Uveitis, Scleritis, Chemical and Drug Induced Liver Injury, CTLA-4 Antigen, Antibodies, Monoclonal, Humanized

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Management of Immune-Related Adverse Events and Kinetics of Response With Ipilimumab

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