Review
. 2015 Jun; 166(5):412-24.
doi: 10.1016/j.trsl.2015.06.005.

Immune-mediated adverse events of anticytotoxic T lymphocyte-associated antigen 4 antibody therapy in metastatic melanoma

Shannon K Quirk 1 Anna K Shure 1 Devendra K Agrawal 2 
Affiliations
  • PMID: 26118951
  •     100 References
  •     16 citations

Abstract

Ipilimumab, an antibody that blocks cytotoxic T lymphocyte-associated antigen 4 (CTLA-4; CD152), was approved by the Food and Drug Administration in 2011 for the treatment of unresectable stage III or IV malignant melanoma. Although the addition of this particular immunotherapy has broadened treatment options, immune-related adverse events (irAEs) are associated with ipilimumab therapy, including dermatologic effects, colitis and diarrhea, endocrine effects, hepatotoxicity, ocular effects, renal effects, neurologic effects, and others. In this article, a critical evaluation of the underlying mechanisms of irAEs associated with anti-CTLA-4 therapy is presented. Additionally, potentially beneficial effects of combinational therapies to alleviate ipilimumab-induced irAEs in malignant melanoma are discussed. Future research is warranted to elucidate the efficacy of such combination therapies and specific biomarkers that would help to predict a clinical response to ipilimumab in patients with malignant melanoma.

Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade.
Yoshiko Iwai, Masayoshi Ishida, +3 authors, Nagahiro Minato.
Proc Natl Acad Sci U S A, 2002 Sep 10; 99(19). PMID: 12218188    Free PMC article.
Highly Cited.
Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4.
Peter Attia, Giao Q Phan, +14 authors, Steven A Rosenberg.
J Clin Oncol, 2005 Aug 10; 23(25). PMID: 16087944    Free PMC article.
Highly Cited.
Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer.
Joseph A Blansfield, Kimberly E Beck, +9 authors, Richard M Sherry.
J Immunother, 2005 Oct 15; 28(6). PMID: 16224277    Free PMC article.
Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4.
Kimberly E Beck, Joseph A Blansfield, +12 authors, James C Yang.
J Clin Oncol, 2006 May 20; 24(15). PMID: 16710025    Free PMC article.
Highly Cited.
Intrapatient dose escalation of anti-CTLA-4 antibody in patients with metastatic melanoma.
Ajay V Maker, James C Yang, +11 authors, Steven A Rosenberg.
J Immunother, 2006 Jun 27; 29(4). PMID: 16799341    Free PMC article.
Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis.
James C Yang, Marybeth Hughes, +10 authors, Steven A Rosenberg.
J Immunother, 2007 Dec 01; 30(8). PMID: 18049334    Free PMC article.
Highly Cited.
Anti-CTLA4 monoclonal antibody induced sarcoidosis in a metastatic melanoma patient.
A Eckert, A Schoeffler, +3 authors, L Thomas.
Dermatology, 2008 Oct 04; 218(1). PMID: 18832811
Immune-mediated red cell aplasia after anti-CTLA-4 immunotherapy for metastatic melanoma.
Ilyssa O Gordon, Takisha Wade, +2 authors, Thomas F Gajewski.
Cancer Immunol Immunother, 2008 Dec 05; 58(8). PMID: 19052742
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.
Anna Maria Di Giacomo, Riccardo Danielli, +8 authors, Michele Maio.
Cancer Immunol Immunother, 2009 Jan 14; 58(8). PMID: 19139884
Inflammatory enteric neuropathy with severe constipation after ipilimumab treatment for melanoma: a case report.
Shailender Bhatia, Bertrand R Huber, Melissa P Upton, John A Thompson.
J Immunother, 2009 Feb 25; 32(2). PMID: 19238020
Neutropenia in a patient treated with ipilimumab (anti-CTLA-4 antibody).
Mojtaba Akhtari, Edmund K Waller, +4 authors, Martha L Arellano.
J Immunother, 2009 Feb 27; 32(3). PMID: 19242368
Melan-A-specific cytotoxic T cells are associated with tumor regression and autoimmunity following treatment with anti-CTLA-4.
Oliver Klein, Lisa M Ebert, +11 authors, Jonathan Cebon.
Clin Cancer Res, 2009 Mar 26; 15(7). PMID: 19318477
Anti-CTLA4 antibody-induced lupus nephritis.
Fouad Fadel, Khalil El Karoui, Bertrand Knebelmann.
N Engl J Med, 2009 Jul 10; 361(2). PMID: 19587352
Phase II trial of tremelimumab (CP-675,206) in patients with advanced refractory or relapsed melanoma.
John M Kirkwood, Paul Lorigan, +7 authors, Cecile A Bulanhagui.
Clin Cancer Res, 2010 Jan 21; 16(3). PMID: 20086001
Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study.
S J O'Day, M Maio, +13 authors, J D Wolchok.
Ann Oncol, 2010 Feb 12; 21(8). PMID: 20147741
Highly Cited.
Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates.
Julie R Brahmer, Charles G Drake, +17 authors, Suzanne L Topalian.
J Clin Oncol, 2010 Jun 03; 28(19). PMID: 20516446    Free PMC article.
Highly Cited.
Improved survival with ipilimumab in patients with metastatic melanoma.
F Stephen Hodi, Steven J O'Day, +26 authors, Walter J Urba.
N Engl J Med, 2010 Jun 08; 363(8). PMID: 20525992    Free PMC article.
Highly Cited.
Treatment and side effect management of CTLA-4 antibody therapy in metastatic melanoma.
Katharina C Kähler, Axel Hauschild.
J Dtsch Dermatol Ges, 2010 Nov 19; 9(4). PMID: 21083648
Review.
Blockade of cytotoxic T-lymphocyte antigen-4 by ipilimumab results in dysregulation of gastrointestinal immunity in patients with advanced melanoma.
David Berman, Susan M Parker, +5 authors, Hanlin L Wang.
Cancer Immun, 2010 Nov 26; 10. PMID: 21090563    Free PMC article.
Ipilimumab experience in heavily pretreated patients with melanoma in an expanded access program at the University Hospital of Siena (Italy).
Anna Maria Di Giacomo, Riccardo Danielli, +10 authors, Michele Maio.
Cancer Immunol Immunother, 2010 Dec 21; 60(4). PMID: 21170646
Drug-induced graves disease from CTLA-4 receptor suppression.
Gary Borodic, David M Hinkle, Yihong Cia.
Ophthalmic Plast Reconstr Surg, 2011 Jan 19; 27(4). PMID: 21242854
Anti-CTLA-4 antibody-induced Guillain-Barré syndrome in a melanoma patient.
S Wilgenhof, B Neyns.
Ann Oncol, 2011 Mar 02; 22(4). PMID: 21357649
Ipilimumab plus dacarbazine for previously untreated metastatic melanoma.
Caroline Robert, Luc Thomas, +21 authors, Jedd D Wolchok.
N Engl J Med, 2011 Jun 07; 364(26). PMID: 21639810
Highly Cited.
Ipilimumab: an anti-CTLA-4 antibody for metastatic melanoma.
Evan J Lipson, Charles G Drake.
Clin Cancer Res, 2011 Sep 09; 17(22). PMID: 21900389    Free PMC article.
Highly Cited. Review.
Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab.
Jianda Yuan, Matthew Adamow, +16 authors, Sacha Gnjatic.
Proc Natl Acad Sci U S A, 2011 Sep 22; 108(40). PMID: 21933959    Free PMC article.
Highly Cited.
Hemophilia A induced by ipilimumab.
Julie Delyon, Christine Mateus, Thierry Lambert.
N Engl J Med, 2011 Nov 04; 365(18). PMID: 22047582
Safety and clinical activity of ipilimumab in melanoma patients with brain metastases: retrospective analysis of data from a phase 2 trial.
Jeffrey S Weber, Asim Amin, +3 authors, Steven J O'Day.
Melanoma Res, 2011 Nov 05; 21(6). PMID: 22051508
Blockade of cytotoxic T-lymphocyte antigen-4 by ipilimumab is associated with a profound long-lasting depletion of Foxp3+ regulatory T cells: a mechanistic explanation for ipilimumab-induced severe enterocolitis?
S Nancey, G Boschetti, +7 authors, B Flourié.
Inflamm Bowel Dis, 2011 Nov 10; 18(8). PMID: 22069060
Ipilimumab-induced sarcoidosis in a patient with metastatic melanoma undergoing complete remission.
Wouter V Vogel, Aurelie Guislain, +3 authors, Christian U Blank.
J Clin Oncol, 2011 Nov 30; 30(2). PMID: 22124094
Posterior reversible encephalopathy syndrome during ipilimumab therapy for malignant melanoma.
Michela Maur, Chiara Tomasello, +3 authors, Pierfranco Conte.
J Clin Oncol, 2011 Dec 29; 30(6). PMID: 22203769
Severe meningo-radiculo-neuritis associated with ipilimumab.
Flavie Bompaire, Christine Mateus, +8 authors, Damien Ricard.
Invest New Drugs, 2012 Jan 11; 30(6). PMID: 22231551
Novel treatments for metastatic cutaneous melanoma and the management of emergent toxicities.
Charlotte Lemech, Hendrik-Tobias Arkenau.
Clin Med Insights Oncol, 2012 Jan 19; 6. PMID: 22253555    Free PMC article.
Hypophysitis induced by monoclonal antibodies to cytotoxic T lymphocyte antigen 4: challenges from a new cause of a rare disease.
Francesco Torino, Agnese Barnabei, +2 authors, Salvatore M Corsello.
Oncologist, 2012 Apr 06; 17(4). PMID: 22477725    Free PMC article.
Review.
Sarcoidosis in a patient with metastatic melanoma sequentially treated with anti-CTLA-4 monoclonal antibody and selective BRAF inhibitor.
Sofie Wilgenhof, Veerle Morlion, +6 authors, Bart Neyns.
Anticancer Res, 2012 Apr 12; 32(4). PMID: 22493370
Ipilimumab: a novel immunomodulating therapy causing autoimmune hypophysitis: a case report and review.
Agata Juszczak, Avinash Gupta, +2 authors, Ashley B Grossman.
Eur J Endocrinol, 2012 Apr 13; 167(1). PMID: 22495490
Review.
Management of immune-related adverse events and kinetics of response with ipilimumab.
Jeffrey S Weber, Katharina C Kähler, Axel Hauschild.
J Clin Oncol, 2012 May 23; 30(21). PMID: 22614989
Highly Cited. Review.
Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
Suzanne L Topalian, F Stephen Hodi, +27 authors, Mario Sznol.
N Engl J Med, 2012 Jun 05; 366(26). PMID: 22658127    Free PMC article.
Highly Cited.
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.
Julie R Brahmer, Scott S Tykodi, +23 authors, Jon M Wigginton.
N Engl J Med, 2012 Jun 05; 366(26). PMID: 22658128    Free PMC article.
Highly Cited.
Ipilimumab-induced immune-related renal failure--a case report.
Patrick M Forde, Kathy Rock, Graham Wilson, Kenneth J O'Byrne.
Anticancer Res, 2012 Oct 13; 32(10). PMID: 23060594
Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody.
Evan J Lipson, William H Sharfman, +10 authors, Suzanne L Topalian.
Clin Cancer Res, 2012 Nov 22; 19(2). PMID: 23169436    Free PMC article.
Highly Cited.
A severe case of ipilimumab-induced guillain-barré syndrome revealed by an occlusive enteric neuropathy: a differential diagnosis for ipilimumab-induced colitis.
Caroline Gaudy-Marqueste, Sandrine Monestier, +3 authors, Jean-Jacques Grob.
J Immunother, 2012 Dec 06; 36(1). PMID: 23211620
Elevated rates of transaminitis during ipilimumab therapy for metastatic melanoma.
Sebastian G Bernardo, Marina Moskalenko, +7 authors, Yvonne M Saenger.
Melanoma Res, 2012 Dec 25; 23(1). PMID: 23262440
Sarcoidosis complicating anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody biotherapy.
Claire Tissot, Ania Carsin, +2 authors, Gilles Devouassoux.
Eur Respir J, 2013 Jan 02; 41(1). PMID: 23277525
Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.
Antoni Ribas, Richard Kefford, +21 authors, Axel Hauschild.
J Clin Oncol, 2013 Jan 09; 31(5). PMID: 23295794    Free PMC article.
Highly Cited.
The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network.
Caroline J Voskens, Simone M Goldinger, +33 authors, Lucie M Heinzerling.
PLoS One, 2013 Jan 24; 8(1). PMID: 23341990    Free PMC article.
Highly Cited.
Ipilimumab associated hepatitis: imaging and clinicopathologic findings.
Kyung Won Kim, Nikhil H Ramaiya, +4 authors, Nageatte Ibrahim.
Invest New Drugs, 2013 Feb 15; 31(4). PMID: 23408334
Endocrine side effects induced by immune checkpoint inhibitors.
Salvatore Maria Corsello, Agnese Barnabei, +3 authors, Francesco Torino.
J Clin Endocrinol Metab, 2013 Mar 09; 98(4). PMID: 23471977
Highly Cited. Review.
Pruritus to anticancer agents targeting the EGFR, BRAF, and CTLA-4.
Alyssa Fischer, Alyx C Rosen, +2 authors, Mario E Lacouture.
Dermatol Ther, 2013 Apr 05; 26(2). PMID: 23551370
Review.
Ipilimumab-induced perforating colitis.
Kisha A Mitchell, Harriet Kluger, Mario Sznol, Douglas J Hartman.
J Clin Gastroenterol, 2013 May 02; 47(9). PMID: 23632354    Free PMC article.
Association of CTLA-4 polymorphisms with improved overall survival in melanoma patients treated with CTLA-4 blockade: a pilot study.
P Queirolo, A Morabito, +9 authors, M P Pistillo.
Cancer Invest, 2013 May 07; 31(5). PMID: 23641913
Reply Re: "Drug-induced Graves disease from CTLA-4 receptor suppression".
Gary E Borodic, David M Hinkle.
Ophthalmic Plast Reconstr Surg, 2013 May 09; 29(3). PMID: 23652295
Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma.
Omid Hamid, Caroline Robert, +23 authors, Antoni Ribas.
N Engl J Med, 2013 Jun 04; 369(2). PMID: 23724846    Free PMC article.
Highly Cited.
Nivolumab plus ipilimumab in advanced melanoma.
Jedd D Wolchok, Harriet Kluger, +21 authors, Mario Sznol.
N Engl J Med, 2013 Jun 04; 369(2). PMID: 23724867    Free PMC article.
Highly Cited.
Severe adverse events from the treatment of advanced melanoma: a systematic review of severe side effects associated with ipilimumab, vemurafenib, interferon alfa-2b, dacarbazine and interleukin-2.
Chelsea Ma, April W Armstrong.
J Dermatolog Treat, 2013 Jun 15; 25(5). PMID: 23763243
Systematic Review.
Ipilimumab and its toxicities: a multidisciplinary approach.
Leslie A Fecher, Sanjiv S Agarwala, F Stephen Hodi, Jeffrey S Weber.
Oncologist, 2013 Jun 19; 18(6). PMID: 23774827    Free PMC article.
Highly Cited. Review.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981    Free PMC article.
Highly Cited.
Efficacy and safety of ipilimumab in metastatic melanoma patients surviving more than 2 years following treatment in a phase III trial (MDX010-20).
D McDermott, J Haanen, +3 authors, MDX010-20 investigators.
Ann Oncol, 2013 Aug 15; 24(10). PMID: 23942774
Ipilimumab granulomatous interstitial nephritis.
Bijin Thajudeen, Machaiah Madhrira, Erika Bracamonte, Lee D Cranmer.
Am J Ther, 2013 Sep 27; 22(3). PMID: 24067875
Cutaneous and pulmonary sarcoidosis-like reaction associated with ipilimumab.
Ross B Reule, Jeffrey P North.
J Am Acad Dermatol, 2013 Oct 16; 69(5). PMID: 24124863
Ipilimumab immune-related adverse reactions: a case report.
Laura Anderson, Vishal Bhatia.
S D Med, 2013 Nov 02; 66(8). PMID: 24175496
Immune modulation in cancer with antibodies.
David B Page, Michael A Postow, +2 authors, Jedd D Wolchok.
Annu Rev Med, 2013 Nov 06; 65. PMID: 24188664
Highly Cited. Review.
Anti-cytotoxic T lymphocyte antigen-4 antibodies in melanoma.
Giulio Tosti, Emilia Cocorocchio, Elisabetta Pennacchioli.
Clin Cosmet Investig Dermatol, 2013 Nov 10; 6. PMID: 24204168    Free PMC article.
Review.
Immune-mediated adverse events associated with ipilimumab ctla-4 blockade therapy: the underlying mechanisms and clinical management.
Ahmad Tarhini.
Scientifica (Cairo), 2013 Nov 28; 2013. PMID: 24278787    Free PMC article.
Highly Cited. Review.
Cancer statistics, 2014.
Rebecca Siegel, Jiemin Ma, Zhaohui Zou, Ahmedin Jemal.
CA Cancer J Clin, 2014 Jan 09; 64(1). PMID: 24399786
Highly Cited.
Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma.
Bing Liao, Sheetal Shroff, Carlos Kamiya-Matsuoka, Sudhakar Tummala.
Neuro Oncol, 2014 Feb 01; 16(4). PMID: 24482447    Free PMC article.
Highly Cited.
Ipilimumab in the treatment of metastatic melanoma: management of adverse events.
Giuseppina Della Vittoria Scarpati, Celeste Fusciello, +4 authors, Stefano Pepe.
Onco Targets Ther, 2014 Feb 27; 7. PMID: 24570590    Free PMC article.
Review.
Lactate dehydrogenase as a selection criterion for ipilimumab treatment in metastatic melanoma.
Sander Kelderman, Bianca Heemskerk, +18 authors, Christian U Blank.
Cancer Immunol Immunother, 2014 Mar 13; 63(5). PMID: 24609989
Highly Cited.
Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution.
Mabel Ryder, Margaret Callahan, +2 authors, James A Fagin.
Endocr Relat Cancer, 2014 Mar 13; 21(2). PMID: 24610577    Free PMC article.
Highly Cited. Review.
Ipilimumab-induced autoimmune adrenalitis.
Le Min, Nageatte Ibrahim.
Lancet Diabetes Endocrinol, 2014 Mar 14; 1(3). PMID: 24622375    Free PMC article.
Ipilimumab-associated Sweet syndrome in a patient with high-risk melanoma.
Rachel L Kyllo, Mary Kendall Parker, Ilana Rosman, Amy C Musiek.
J Am Acad Dermatol, 2014 Mar 19; 70(4). PMID: 24629370
Review.
Kidney injuries related to ipilimumab.
Hassane Izzedine, Victor Gueutin, +6 authors, Philippe Rouvier.
Invest New Drugs, 2014 Apr 02; 32(4). PMID: 24687600
Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody.
Shintaro Iwama, Alessandra De Remigis, +3 authors, Patrizio Caturegli.
Sci Transl Med, 2014 Apr 04; 6(230). PMID: 24695685
Highly Cited.
Ipilimumab in patients with cancer and the management of dermatologic adverse events.
Mario E Lacouture, Jedd D Wolchok, +3 authors, Axel Hauschild.
J Am Acad Dermatol, 2014 Apr 29; 71(1). PMID: 24767731
Review.
Myasthenia Gravis Induced by Ipilimumab in Patients With Metastatic Melanoma.
Douglas B Johnson, Vita Saranga-Perry, +7 authors, Jeffrey A Sosman.
J Clin Oncol, 2014 Apr 30; 33(33). PMID: 24778401    Free PMC article.
A case report of orbital inflammatory syndrome secondary to ipilimumab.
Amanda D Henderson, Dilip A Thomas.
Ophthalmic Plast Reconstr Surg, 2014 May 13; 31(3). PMID: 24814274
Ipilimumab-induced colonic perforation.
Lyle Burdine, Keith Lai, Jonathan A Laryea.
J Surg Case Rep, 2014 May 31; 2014(3). PMID: 24876393    Free PMC article.
New-onset mediastinal and central nervous system sarcoidosis in a patient with metastatic melanoma undergoing CTLA4 monoclonal antibody treatment.
Kevin P Murphy, Marcus P Kennedy, +2 authors, Derek G Power.
Oncol Res Treat, 2014 Jun 07; 37(6). PMID: 24903767
A review of novel therapies for melanoma.
Chante Karimkhani, Rene Gonzalez, Robert P Dellavalle.
Am J Clin Dermatol, 2014 Jun 15; 15(4). PMID: 24928310
Review.
Serious haematological toxicity during and after ipilimumab treatment: a case series.
Ester Simeone, Antonio Maria Grimaldi, +5 authors, Paolo Antonio Ascierto.
J Med Case Rep, 2014 Jul 06; 8. PMID: 24986059    Free PMC article.
Opportunistic infections in patients treated with immunotherapy for cancer.
Chrisann Kyi, Matthew D Hellmann, +2 authors, Michael A Postow.
J Immunother Cancer, 2014 Jul 06; 2. PMID: 24991413    Free PMC article.
Dermatologic adverse events to chemotherapeutic agents, Part 2: BRAF inhibitors, MEK inhibitors, and ipilimumab.
Jennifer Nam Choi.
Semin Cutan Med Surg, 2014 Jul 20; 33(1). PMID: 25037257
Review.
Ipilimumab-induced hypophysitis: a detailed longitudinal analysis in a large cohort of patients with metastatic melanoma.
Alexander T Faje, Ryan Sullivan, +4 authors, Lisa Nachtigall.
J Clin Endocrinol Metab, 2014 Aug 01; 99(11). PMID: 25078147
Highly Cited.
Ipilimumab treatment associated pituitary hypophysitis: clinical presentation and imaging diagnosis.
Yosef Chodakiewitz, Sanford Brown, +2 authors, Jeffrey M Rogg.
Clin Neurol Neurosurg, 2014 Aug 16; 125. PMID: 25127260
Review.
Thyroid-like ophthalmopathy in a euthyroid patient receiving Ipilimumab.
Elizabeth McElnea, Aine Ní Mhéalóid, +2 authors, Tim Fulcher.
Orbit, 2014 Sep 11; 33(6). PMID: 25207976
Severe relapse in a multiple sclerosis patient associated with ipilimumab treatment of melanoma.
Edward J Gettings, Christopher T Hackett, Thomas F Scott.
Mult Scler, 2014 Sep 27; 21(5). PMID: 25257614
Drug-associated dermatomyositis following ipilimumab therapy: a novel immune-mediated adverse event associated with cytotoxic T-lymphocyte antigen 4 blockade.
Shirwa Sheik Ali, Allison L Goddard, +4 authors, Ruth Ann Vleugels.
JAMA Dermatol, 2014 Oct 17; 151(2). PMID: 25321335
Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic melanoma: a randomized clinical trial.
F Stephen Hodi, Sandra Lee, +7 authors, John M Kirkwood.
JAMA, 2014 Nov 05; 312(17). PMID: 25369488    Free PMC article.
Highly Cited.
Genetic basis for clinical response to CTLA-4 blockade in melanoma.
Alexandra Snyder, Vladimir Makarov, +18 authors, Timothy A Chan.
N Engl J Med, 2014 Nov 20; 371(23). PMID: 25409260    Free PMC article.
Highly Cited.
Long-term follow-up of ipilimumab-induced hypophysitis, a common adverse event of the anti-CTLA-4 antibody in melanoma.
Frédérique Albarel, Caroline Gaudy, +5 authors, Thierry Brue.
Eur J Endocrinol, 2014 Nov 25; 172(2). PMID: 25416723
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients.
Roy S Herbst, Jean-Charles Soria, +19 authors, F Stephen Hodi.
Nature, 2014 Nov 28; 515(7528). PMID: 25428504    Free PMC article.
Highly Cited.
Ipilimumab-associated Sweet syndrome in a melanoma patient.
Rachel Gormley, Karolyn Wanat, +4 authors, Junko Takeshita.
J Am Acad Dermatol, 2014 Dec 02; 71(5). PMID: 25437997
Systemic high-dose corticosteroid treatment does not improve the outcome of ipilimumab-related hypophysitis: a retrospective cohort study.
Le Min, Frank Stephen Hodi, +6 authors, Ursula B Kaiser.
Clin Cancer Res, 2014 Dec 30; 21(4). PMID: 25538262    Free PMC article.
Treatment possibilities of ipilimumab-induced thrombocytopenia--case study and literature review.
Jindřich Kopecký, Petronela Trojanová, Ondřej Kubeček, Otakar Kopecký.
Jpn J Clin Oncol, 2015 Jan 15; 45(4). PMID: 25583422
Review.
Late development of splenic sarcoidosis-like lesions in a patient with metastatic melanoma and long-lasting clinical response to ipilimumab.
Rikke Andersen, Peter Nørgaard, Mohamad Kadhem Mohamad Al-Jailawi, Inge Marie Svane.
Oncoimmunology, 2015 Jan 23; 3(8). PMID: 25610749    Free PMC article.
Ipilimumab-associated bilateral optic neuropathy.
Oliver L Yeh, Courtney E Francis.
J Neuroophthalmol, 2015 Feb 04; 35(2). PMID: 25647225
Peripheral neuropathy associated with ipilimumab: a report of 2 cases.
Iyavut Thaipisuttikul, Paul Chapman, Edward K Avila.
J Immunother, 2015 Feb 07; 38(2). PMID: 25658617    Free PMC article.
Impact of NRAS mutations for patients with advanced melanoma treated with immune therapies.
Douglas B Johnson, Christine M Lovly, +12 authors, Jeffrey A Sosman.
Cancer Immunol Res, 2015 Mar 05; 3(3). PMID: 25736262    Free PMC article.
Highly Cited.
Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial.
Jeffrey S Weber, Sandra P D'Angelo, +25 authors, James Larkin.
Lancet Oncol, 2015 Mar 22; 16(4). PMID: 25795410
Highly Cited.
Anti-CTLA-4 (CD 152) monoclonal antibody-induced autoimmune interstitial nephritis.
Elaine C Jolly, Menna R Clatworthy, +2 authors, Ken Farrington.
NDT Plus, 2009 Aug 01; 2(4). PMID: 25984021    Free PMC article.
Infectious Colitis Associated With Ipilimumab Therapy.
Jessica L McCutcheon, Colt M McClain, Igor Puzanov, Terrence A Smith.
Gastroenterology Res, 2014 Feb 01; 7(1). PMID: 27785266    Free PMC article.
Enhancing the safety of antibody-based immunomodulatory cancer therapy without compromising therapeutic benefit: Can we have our cake and eat it too?
Joseph M Ryan, Jeffrey S Wasser, Adam J Adler, Anthony T Vella.
Expert Opin Biol Ther, 2016 Feb 09; 16(5). PMID: 26855028    Free PMC article.
Review.
Profiling the dynamic expression of checkpoint molecules on cytokine-induced killer cells from non-small-cell lung cancer patients.
Lin Zhang, Jian Wang, +13 authors, Xiubao Ren.
Oncotarget, 2016 Jun 11; 7(28). PMID: 27283895    Free PMC article.
Targeted therapies for the treatment of non-small-cell lung cancer: Monoclonal antibodies and biological inhibitors.
Ana P S Silva, Priscila V Coelho, Maristella Anazetti, Patricia U Simioni.
Hum Vaccin Immunother, 2016 Nov 11; 13(4). PMID: 27831000    Free PMC article.
Review.
Neurological and Neuropsychiatric Adverse Effects of Dermatologic Medications.
Melinda Liu, Yuan Yu M Huang, Sylvia Hsu, Joseph S Kass.
CNS Drugs, 2016 Nov 11; 30(12). PMID: 27832476
Review.
Ipilimumab-Induced Enteritis without Colitis: A New Challenge.
Marcus Messmer, Sunita Upreti, +4 authors, Matthias Holdhoff.
Case Rep Oncol, 2016 Dec 07; 9(3). PMID: 27920706    Free PMC article.
Cancer immunotherapy - immune checkpoint blockade and associated endocrinopathies.
David J Byun, Jedd D Wolchok, Lynne M Rosenberg, Monica Girotra.
Nat Rev Endocrinol, 2017 Jan 21; 13(4). PMID: 28106152    Free PMC article.
Highly Cited. Review.
Prospects for combined use of oncolytic viruses and CAR T-cells.
Adam Ajina, John Maher.
J Immunother Cancer, 2017 Nov 22; 5(1). PMID: 29157300    Free PMC article.
Review.
Improving anti-melanoma effect of curcumin by biodegradable nanoparticles.
Bilan Wang, Xiaoxiao Liu, +6 authors, Yangmei Shen.
Oncotarget, 2018 Jan 10; 8(65). PMID: 29312556    Free PMC article.
The Current Understanding of the Endocrine Effects From Immune Checkpoint Inhibitors and Recommendations for Management.
Monica Girotra, Aaron Hansen, +10 authors, Investigational Drug Steering Committee (IDSC) Immunotherapy Task Force collaboration.
JNCI Cancer Spectr, 2018 Jul 31; 2(3). PMID: 30057972    Free PMC article.
Review.
Toxicities of Immune Checkpoint Inhibitors: Itis-Ending Adverse Reactions and More.
Moataz Ellithi, Radowan Elnair, Guy Vin Chang, Mohamed A Abdallah.
Cureus, 2020 Mar 20; 12(2). PMID: 32190487    Free PMC article.
Review.
Ipilimumab and Nivolumab induced steroid-refractory colitis treated with infliximab: A case report.
Ammar B Nassri, Valery Muenyi, +4 authors, Silvio W de Melo.
World J Gastrointest Pharmacol Ther, 2019 Jan 31; 10(1). PMID: 30697447    Free PMC article.
Diagnosis and Management of Hematological Adverse Events Induced by Immune Checkpoint Inhibitors: A Systematic Review.
Nabil E Omar, Kareem A El-Fass, +8 authors, Said Dermime.
Front Immunol, 2020 Nov 17; 11. PMID: 33193289    Free PMC article.
Systematic Review.
Immune Thrombocytopenia Induced by Immune Checkpoint Inhibitors in Solid Cancer: Case Report and Literature Review.
Xiaolin Liu, Xiuju Liang, +2 authors, Jun Wang.
Front Oncol, 2020 Dec 29; 10. PMID: 33365266    Free PMC article.
Inflammation and tumor progression: signaling pathways and targeted intervention.
Huakan Zhao, Lei Wu, +4 authors, Yongsheng Li.
Signal Transduct Target Ther, 2021 Jul 13; 6(1). PMID: 34248142    Free PMC article.
Immune-mediated thrombocytopenia induced with durvalumab after chemoradiotherapy in a non-small cell lung cancer patient: A case report.
Tomonori Makiguchi, Hisashi Tanaka, +3 authors, Sadatomo Tasaka.
Thorac Cancer, 2021 Aug 19; 12(20). PMID: 34405563    Free PMC article.
Immune Thrombocytopenia Induced by Immune Checkpoint Inhibitrs in Lung Cancer: Case Report and Literature Review.
Wang Xie, NaNa Hu, LeJie Cao.
Front Immunol, 2021 Dec 28; 12. PMID: 34956221    Free PMC article.
Review.