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Patient Responses To Ipilimumab, A Novel Immunopotentiator For Metastatic Melanoma: How Different Are These From Conventional Treatment Responses?

G. Pennock, W. Waterfield, J. Wolchok
Published 2012 · Medicine

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Advanced melanoma has defied treatment advances for several decades. Immunotherapy with high-dose interleukin-2 or interferon-&agr; has been beneficial in some cases, but significant toxicities limit its use. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) signaling switches off T-cell activation and induces immune tolerance. Inhibiting CTLA-4 prolongs the antitumor T-cell response, reversing tolerance. Ipilimumab is a first-in-class anti-CTLA-4 monoclonal antibody, currently under review by the Food and Drug Administration for pretreated melanoma. Ipilimumab has shown durable responses and manageable toxicities in a large phase 3 clinical trial in patients with advanced melanoma. Variable response patterns have been observed, including: (1) response in baseline lesions; (2) a slow, steady decline in tumor burden; (3) response after an increase in tumor burden; and (4) response in index and new lesions accompanied by the appearance of other new lesions. Although responses (1) and (2) may be captured using standard methods, atypical responses (3) and (4) would be classified as progressive disease using conventional assessments. Patients on ipilimumab may have delayed responses or durable stable disease even after apparent disease progression, therefore using new immune-related response criteria is recommended to avoid premature treatment withdrawal. This review compares and contrasts responses to ipilimumab with those after chemotherapy, and discusses treatment implications.
This paper references
10.1002/cncr.24951
Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting
G. Ku (2010)
10.1016/S0093-3619(08)79036-1
Prognostic Factors Related to Clinical Response in Patients with Metastatic Melanoma Treated by CTL-Associated Antigen-4 Blockade
B. Thiers (2009)
10.1002/cncr.23251
Practical guidelines for the management of interferon‐α‐2b side effects in patients receiving adjuvant treatment for melanoma
A. Hauschild (2008)
10.1200/JCO.2008.17.8954
Anti-cytotoxic T-lymphocyte antigen-4 antibody: the first in an emerging class of immunomodulatory antibodies for cancer treatment.
L. Fong (2008)
10.1002/ijc.21264
Phase 1/2 study of subcutaneous and intradermal immunization with a recombinant MAGE‐3 protein in patients with detectable metastatic melanoma
W. Kruit (2005)
A phase II multicenter study of ipilimumab with or without dacarbazine in chemotherapynaïve patients with advanced melanoma
E M Hersh (2010)
10.1200/JCO.2010.28.18_SUPPL.4
A phase III, randomized, double-blind, multicenter study comparing monotherapy with ipilimumab or gp100 peptide vaccine and the combination in patients with previously treated, unresectable stage III or IV melanoma.
S. O'Day (2010)
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)
10.1007/s00262-004-0526-8
The paradox of T cell–mediated antitumor immunity in spite of poor clinical outcome in human melanoma
A. Anichini (2004)
10.1056/NEJMoa1003466
Improved survival with ipilimumab in patients with metastatic melanoma.
F. S. Hodi (2010)
10.1016/S0952-7915(00)00195-3
Immunity against cancer: lessons learned from melanoma.
A. Houghton (2001)
10.1073/pnas.0712237105
Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients
F. S. Hodi (2008)
A phase II multicenter study of ipilimumab with or without dacarbazine in chemotherapynaı̈ve patients with advanced melanoma
EM Hersh (2010)
10.1097/CJI.0b013e318156e47e
Ipilimumab (Anti-CTLA4 Antibody) Causes Regression of Metastatic Renal Cell Cancer Associated With Enteritis and Hypophysitis
J. Yang (2007)
10.1200/JCO.2010.28.15_SUPPL.8509
Re-induction with ipilimumab, gp100 peptide vaccine, or a combination of both from a phase III, randomized, double-blind, multicenter study of previously treated patients with unresectable stage III or IV melanoma.
F. S. Hodi (2010)
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)
10.1073/pnas.1533209100
Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma
G. Phan (2003)
10.1158/0008-5472.CAN-05-4128
Tumor-driven evolution of immunosuppressive networks during malignant progression.
R. Kim (2006)
10.1200/JCO.2008.16.5449
Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens.
M. Dudley (2008)
10.1007/s00262-008-0653-8
Ipilimumab: controversies in its development, utility and autoimmune adverse events
J. Weber (2008)
10.1158/1078-0432.CCR-09-2376
Do We Need a Different Set of Response Assessment Criteria for Tumor Immunotherapy?
A. Ribas (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.2005.08.375
Tumoral and immunologic response after vaccination of melanoma patients with an ALVAC virus encoding MAGE antigens recognized by T cells.
N. van Baren (2005)
10.1016/j.gde.2007.12.007
Immune surveillance: a balance between protumor and antitumor immunity.
S. Ostrand-Rosenberg (2008)
10.1016/j.coi.2009.03.002
Adoptive cell therapy for the treatment of patients with metastatic melanoma.
S. Rosenberg (2009)
Single institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting: lymphocyte count after two doses correlates with survival
GY Ku (2012)
10.1016/S0065-2776(06)90002-9
Mechanisms of immune evasion by tumors.
C. Drake (2006)
10.1016/J.SOC.2005.12.008
Evaluation of immunotherapy in the treatment of melanoma.
M. Faries (2006)
Immune therapy of cancer.
E. L. Calhoon (1988)
10.3747/CO.V16I3.447
Adjuvant interferon alfa for melanoma: new evidence-based treatment recommendations?
A. Hauschild (2009)
10.1200/jco.2009.27.15_suppl.9033
Effect of ipilimumab treatment on 18-month survival: Update of patients (pts) with advanced melanoma treated with 10 mg/kg ipilimumab in three phase II clinical trials.
S. O'Day (2009)
Efficacy and safety of ipilimumab monotherapy in patients with previously treated, advanced melanoma: a multicenter, single-arm, phase II study
SJ O’Day (2010)
The heterogeneity of the kinetics of response to ipilimumab in metastatic melanoma: patient cases.
Y. Saenger (2008)
10.1200/JCO.2008.16.1927
Phase I/II study of ipilimumab for patients with metastatic melanoma.
J. Weber (2008)
10.1200/JCO.2008.26.15_SUPPL.3022
Potential immune biomarkers of gastrointestinal toxicities and efficacy in patients with advanced melanoma treated with ipilimumab with or without prophylactic budesonide
D. Berman (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)
10.1016/J.COI.2006.01.011
Principles and use of anti-CTLA4 antibody in human cancer immunotherapy.
K. Peggs (2006)
10.1097/CMR.0b013e328307ee4c
Spontaneous regression of metastases from malignant melanoma: a case report
L. V. Kalialis (2008)
10.1097/01.CJI.0000211341.88835.AE
A clinical development paradigm for cancer vaccines and related biologics.
A. Hoos (2007)
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)
Clinical Practice Guidelines in Oncology . Melanoma , Version 1 . 2010
D Schadendorf
10.1615/CRITREVIMMUNOL.V18.I5.10
CD28/B7 costimulation: a review.
E. Greenfield (1998)
10.1097/01.cji.0000208259.73167.58
Intrapatient Dose Escalation of Anti–CTLA-4 Antibody in Patients With Metastatic Melanoma
A. Maker (2006)
10.1200/JCO.2010.28.15_SUPPL.8523
Phase II trial of ipilimumab monotherapy in melanoma patients with brain metastases.
D. Lawrence (2010)
National Comprehensive Cancer Network: Clinical Practice Guidelines in Oncology. Melanoma, Version 1
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)
10.1200/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)
10.1097/01.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)
10.1093/annonc/mdp253
Immunotherapy of distant metastatic disease
D. Schadendorf (2009)



This paper is referenced by
10.1001/jamaoncol.2017.1588
Nivolumab for Patients With Advanced Melanoma Treated Beyond Progression: Analysis of 2 Phase 3 Clinical Trials
G. Long (2017)
Supplementary Issue: Biomarkers and their Essential Role in the Development of Personalised Therapies (A)
J. Valliant (2016)
10.1586/era.12.132
Ipilimumab in melanoma
P. Specenier (2012)
10.1158/1541-7786.MCR-13-0581
Beneficial Effects of RAF Inhibitor in Mutant BRAF Splice Variant–Expressing Melanoma
Edward J Hartsough (2014)
10.3109/0284186X.2012.682630
Severe colitis while responding to ipilimumab in metastatic melanoma
M. Slingerland (2012)
10.1080/14737140.2016.1211936
Ipilimumab in melanoma
P. Specenier (2016)
10.1002/jcph.591
Immune Checkpoint inhibitors: An introduction to the next‐generation cancer immunotherapy
Lucy Lee (2016)
10.1007/s00259-020-04967-9
The value of 18F-FDG PET/CT for predicting or monitoring immunotherapy response in patients with metastatic melanoma: a systematic review and meta-analysis
Narjess Ayati (2020)
10.1684/bdc.2014.2054
[Immunotherapies and melanoma].
É. Routier (2014)
10.1165/rcmb.2011-0215TR
A current viewpoint of lymphangioleiomyomatosis supporting immunotherapeutic treatment options.
D. Dilling (2012)
10.1634/theoncologist.2013-0171
What lies within: novel strategies in immunotherapy for non-small cell lung cancer.
P. Forde (2013)
10.1345/aph.1R614
Novel Targets in the Treatment of Advanced Melanoma: New First-Line Treatment Options
K. Culos (2013)
10.1517/14656566.2011.629187
Blockade of cytotoxic T-lymphocyte antigen-4 as a new therapeutic approach for advanced melanoma
X. Wang (2011)
10.1016/S1632-3475(17)86846-6
Melanoma cutáneo cervicofacial
A. Moya-Plana (2017)
10.1111/nyas.12180
Development of ipilimumab: a novel immunotherapeutic approach for the treatment of advanced melanoma
J. Wolchok (2013)
10.3978/j.issn.2218-6751.2014.01.01
Immunotherapy in lung cancer.
E. Massarelli (2014)
10.1089/hum.2013.150
Synergistic antitumor effect of recombinant adeno-associated virus-mediated pigment epithelium-derived factor with hyperthermia on solid tumor.
Qinjie Wu (2014)
10.1016/j.phrs.2011.09.002
Ipilimumab: a novel immunostimulatory monoclonal antibody for the treatment of cancer.
G. Graziani (2012)
10.1517/14728222.2011.645807
Metastatic melanoma: the new era of targeted therapy
M. Guida (2012)
10.1186/s12943-018-0757-5
Liquid biomarkers in melanoma: detection and discovery
S. Y. Lim (2018)
10.2217/imt.13.9
Tremelimumab: a review of development to date in solid tumors.
A. Tarhini (2013)
10.1016/J.ARBR.2020.04.003
The Importance of Imaging Studies in the Assessment of Response to Immunotherapy in Lung Cancer
L. Gorospe (2020)
Management of Neurological Adverse Events Associated with Immunotherapy and A Possible Algorithm for Clinical Management
Timothy Allen (2015)
10.1016/S1470-2045(12)70324-8
Ipilimumab and fotemustine in patients with advanced melanoma (NIBIT-M1): an open-label, single-arm phase 2 trial.
A. M. Di Giacomo (2012)
10.1053/j.seminoncol.2014.09.003
Current perspectives on immunotherapy.
J. Weber (2014)
10.1007/978-1-61779-407-0_13
Adoptive Cell Therapy for the Treatment of Metastatic Melanoma
J. Chacon (2012)
Canadian Perspective on the Clinical Management of Metastatic Melanoma
T. Petrella (2012)
10.1007/s00259-014-2848-x
Evaluation of response to immunotherapy: new challenges and opportunities for PET imaging
L. Gilardi (2014)
10.1038/jid.2014.1
Indomethacin to the rescue of TRAIL-resistant melanomas.
R. Somasundaram (2014)
10.1177/000313481408000833
Systematic Review: Surgery for Patients with Metastatic Melanoma during Active Treatment with Ipilimumab
J. Baker (2014)
10.6004/JADPRO.2016.7.5.3
How Checkpoint Inhibitors Are Changing the Treatment Paradigm in Solid Tumors: What Advanced Practitioners in Oncology Need to Know
Marianne Davies (2016)
10.1097/CAD.0000000000000814
Tumour flare reaction in cancer treatments: a comprehensive literature review
Amina Taleb B. (2019)
See more
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