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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
Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting
G. Ku (2010)
Prognostic Factors Related to Clinical Response in Patients with Metastatic Melanoma Treated by CTL-Associated Antigen-4 Blockade
B. Thiers (2009)
Practical guidelines for the management of interferon‐α‐2b side effects in patients receiving adjuvant treatment for melanoma
A. Hauschild (2008)
Anti-cytotoxic T-lymphocyte antigen-4 antibody: the first in an emerging class of immunomodulatory antibodies for cancer treatment.
L. Fong (2008)
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)
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)
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)
The paradox of T cell–mediated antitumor immunity in spite of poor clinical outcome in human melanoma
A. Anichini (2004)
Improved survival with ipilimumab in patients with metastatic melanoma.
F. S. Hodi (2010)
Immunity against cancer: lessons learned from melanoma.
A. Houghton (2001)
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)
Ipilimumab (Anti-CTLA4 Antibody) Causes Regression of Metastatic Renal Cell Cancer Associated With Enteritis and Hypophysitis
J. Yang (2007)
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)
Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4.
Kimberly E. Beck (2006)
Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma
G. Phan (2003)
Tumor-driven evolution of immunosuppressive networks during malignant progression.
R. Kim (2006)
Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens.
M. Dudley (2008)
Ipilimumab: controversies in its development, utility and autoimmune adverse events
J. Weber (2008)
Do We Need a Different Set of Response Assessment Criteria for Tumor Immunotherapy?
A. Ribas (2009)
Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study.
S. O’Day (2010)
Tumoral and immunologic response after vaccination of melanoma patients with an ALVAC virus encoding MAGE antigens recognized by T cells.
N. van Baren (2005)
Immune surveillance: a balance between protumor and antitumor immunity.
S. Ostrand-Rosenberg (2008)
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)
Mechanisms of immune evasion by tumors.
C. Drake (2006)
Evaluation of immunotherapy in the treatment of melanoma.
M. Faries (2006)
Immune therapy of cancer.
E. L. Calhoon (1988)
Adjuvant interferon alfa for melanoma: new evidence-based treatment recommendations?
A. Hauschild (2009)
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)
Phase I/II study of ipilimumab for patients with metastatic melanoma.
J. Weber (2008)
Potential immune biomarkers of gastrointestinal toxicities and efficacy in patients with advanced melanoma treated with ipilimumab with or without prophylactic budesonide
D. Berman (2008)
Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-Related Response Criteria
J. Wolchok (2009)
Principles and use of anti-CTLA4 antibody in human cancer immunotherapy.
K. Peggs (2006)
Spontaneous regression of metastases from malignant melanoma: a case report
L. V. Kalialis (2008)
A clinical development paradigm for cancer vaccines and related biologics.
A. Hoos (2007)
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
CD28/B7 costimulation: a review.
E. Greenfield (1998)
Intrapatient Dose Escalation of Anti–CTLA-4 Antibody in Patients With Metastatic Melanoma
A. Maker (2006)
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
Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study.
J. Wolchok (2010)
Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4.
P. Attia (2005)
Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer.
J. Blansfield (2005)
Immunotherapy of distant metastatic disease
D. Schadendorf (2009)
This paper is referenced by
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)
Ipilimumab in melanoma
P. Specenier (2012)
Beneficial Effects of RAF Inhibitor in Mutant BRAF Splice Variant–Expressing Melanoma
Edward J Hartsough (2014)
Severe colitis while responding to ipilimumab in metastatic melanoma
M. Slingerland (2012)
Ipilimumab in melanoma
P. Specenier (2016)
Immune Checkpoint inhibitors: An introduction to the next‐generation cancer immunotherapy
Lucy Lee (2016)
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)
[Immunotherapies and melanoma].
É. Routier (2014)
A current viewpoint of lymphangioleiomyomatosis supporting immunotherapeutic treatment options.
D. Dilling (2012)
What lies within: novel strategies in immunotherapy for non-small cell lung cancer.
P. Forde (2013)
Novel Targets in the Treatment of Advanced Melanoma: New First-Line Treatment Options
K. Culos (2013)
Blockade of cytotoxic T-lymphocyte antigen-4 as a new therapeutic approach for advanced melanoma
X. Wang (2011)
Melanoma cutáneo cervicofacial
A. Moya-Plana (2017)
Development of ipilimumab: a novel immunotherapeutic approach for the treatment of advanced melanoma
J. Wolchok (2013)
Immunotherapy in lung cancer.
E. Massarelli (2014)
Synergistic antitumor effect of recombinant adeno-associated virus-mediated pigment epithelium-derived factor with hyperthermia on solid tumor.
Qinjie Wu (2014)
Ipilimumab: a novel immunostimulatory monoclonal antibody for the treatment of cancer.
G. Graziani (2012)
Metastatic melanoma: the new era of targeted therapy
M. Guida (2012)
Liquid biomarkers in melanoma: detection and discovery
S. Y. Lim (2018)
Tremelimumab: a review of development to date in solid tumors.
A. Tarhini (2013)
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)
Ipilimumab and fotemustine in patients with advanced melanoma (NIBIT-M1): an open-label, single-arm phase 2 trial.
A. M. Di Giacomo (2012)
Current perspectives on immunotherapy.
J. Weber (2014)
Adoptive Cell Therapy for the Treatment of Metastatic Melanoma
J. Chacon (2012)
Canadian Perspective on the Clinical Management of Metastatic Melanoma
T. Petrella (2012)
Evaluation of response to immunotherapy: new challenges and opportunities for PET imaging
L. Gilardi (2014)
Indomethacin to the rescue of TRAIL-resistant melanomas.
R. Somasundaram (2014)
Systematic Review: Surgery for Patients with Metastatic Melanoma during Active Treatment with Ipilimumab
J. Baker (2014)
How Checkpoint Inhibitors Are Changing the Treatment Paradigm in Solid Tumors: What Advanced Practitioners in Oncology Need to Know
Marianne Davies (2016)
Tumour flare reaction in cancer treatments: a comprehensive literature review
Amina Taleb B. (2019)See more