Safety and Efficacy of Radiation Therapy in Advanced Melanoma Patients Treated With Ipilimumab

Qin, Rosie; Olson, Adam C.; Singh, Bhavana; Thomas, Samantha M.; Wolf, Steven; Bhavsar, Nrupen A.; Hanks, Brent A.; Salama, Joseph K.; Salama, April K.S.

doi:10.1016/j.ijrobp.2016.04.017

Cited by 65 publications

(46 citation statements)

References 14 publications

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“…In 2015 Eggermont et al stated in a phase III clinical trial when ipilimumab is given in an adjuvant manner in previously resected stage III melanoma, it significantly improved recurrence-free survival compared with placebo [170]. In combination with glycoprotein 100 (gp100) vaccination or with radiotherapy, ipilimumab improved overall survival or increased the duration of irradiated tumor response [171–173]. Moreover, in combination with the immunostimulator sargramostim, ipilimumab showed longer overall survival in the same setting [174].…”

Section: Clinical Trials Exploiting Reinvigoration Of T Cellsmentioning

confidence: 99%

T cell exhaustion: from pathophysiological basics to tumor immunotherapy

Klieser²,

et al. 2017

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The immune system is capable of distinguishing between danger- and non-danger signals, thus inducing either an appropriate immune response against pathogens and cancer or inducing self-tolerance to avoid autoimmunity and immunopathology. One of the mechanisms that have evolved to prevent destruction by the immune system, is to functionally silence effector T cells, termed T cell exhaustion, which is also exploited by viruses and cancers for immune escape In this review, we discuss some of the phenotypic markers associated with T cell exhaustion and we summarize current strategies to reinvigorate exhausted T cells by blocking these surface marker using monoclonal antibodies.

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Section: Clinical Trials Exploiting Reinvigoration Of T Cellsmentioning

confidence: 99%

T cell exhaustion: from pathophysiological basics to tumor immunotherapy

Klieser²,

et al. 2017

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“…Although the immunological mechanism and case reports are intriguing, evidence does not yet conclusively establish that the abscopal effect, and subsequent tumor regression, can be induced by a combination of checkpoint blockade and radiation. In one recent study, radiation was found to be tolerated with ipilimumab, although the benefit of dual therapy is not yet well defined 34 .…”

Section: Molecular Correlates Of Melanoma Response To Checkpoint mentioning

confidence: 99%

Immune and molecular correlates in melanoma treated with immune checkpoint blockade

Byrne

Fisher

2017

Cancer

128

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Immunotherapy for metastatic melanoma has a decades-long history, and the relatively recent use of checkpoint inhibitors has revolutionized treatment. Durable, and sometimes complete, remission of metastatic melanoma is now achievable in some patients receiving checkpoint-blocking therapy. However, it is unclear why some patients fare better than others. This review highlights several molecular indicators of response to checkpoint inhibition in metastatic melanoma, focusing on tumor PDL1 expression, MHC I expression, mutational load in the tumor, and T cell infiltration in the tumor. Additionally, clinical correlates of response, notably vitiligo and other immune-related adverse events, can potentially shed light on the mechanisms by which checkpoint blockade may achieve such great success, particularly in melanoma. We propose that MITF – a key regulator of melanocyte survival, melanin production, and melanoma transformation – produces a molecular landscape in melanocytes and melanoma cells that can make melanomas particularly susceptible to checkpoint blockade and also that can also result in immune attack on normal melanocytes.

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“…57,61 One retrospective comparison included 44 patients with advanced melanoma who received ipilimumab alone versus an unmatched cohort of 44 patients who received ipilimumab plus RT. 57 Although there were more adverse clinicopathologic features in the RT group, OS was similar between patients who received ipilimumab alone and those who received ipilimumab combined with RT. There did not appear to be a clinically detectable increase in irAEs with the combination of RT and ipilimumab.…”

Section: Ctla-4 Inhibition With or Without Single-fraction Palliativmentioning

confidence: 99%

“…Few reports have directly compared patients who received ipilimumab alone with a contemporaneous cohort that received ipilimumab plus RT. 57,61 One retrospective comparison included 44 patients with advanced melanoma who received ipilimumab alone versus an unmatched cohort of 44 patients who received ipilimumab plus RT. 57 Although there were more adverse clinicopathologic features in the RT group, OS was similar between patients who received ipilimumab alone and those who received ipilimumab combined with RT.…”

Section: Comparison Of Ctla-4 Alone Versus Ctla-4 and Rtmentioning

confidence: 99%

Irradiation and immunotherapy: From concept to the clinic

Salama

Postow

Salama

2016

Cancer

Self Cite

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In recent years, an increased understanding of T‐cell–regulatory mechanisms has led to the development of a novel class of immune‐checkpoint inhibitors that have robust clinical activity against a broad array of malignancies—even those that historically were not believed to be sensitive to immune therapy. With this, there has been renewed interest in the potential for synergy with more traditional forms of anticancer therapy like radiation therapy (RT). The role of RT in palliation or as definitive treatment for certain malignancies has been well established. Yet, in recent years, the concept has come to light that RT could be an attractive partner for use in combination with other immunotherapies. The effects of RT include not only control of an irradiated tumor but also multiple immunomodulatory effects on both the tumor and the microenvironment, priming tumors for an immune‐mediated response. Herein, the authors summarize relevant preclinical data and rationale supporting the synergy of combined RT and immunotherapy and highlight recent clinical work on promising combination strategies. Cancer 2016;122:1659‐71. © 2016 American Cancer Society.

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Safety and Efficacy of Radiation Therapy in Advanced Melanoma Patients Treated With Ipilimumab

Cited by 65 publications

References 14 publications

T cell exhaustion: from pathophysiological basics to tumor immunotherapy

T cell exhaustion: from pathophysiological basics to tumor immunotherapy

Immune and molecular correlates in melanoma treated with immune checkpoint blockade

Irradiation and immunotherapy: From concept to the clinic

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