Malignant melanoma—The cradle of anti-neoplastic immunotherapy

Koller, Kristian Michael; Wang, Wenge; Schell, Todd D.; Cozza, Eugene M.; Kokolus, Kathleen M.; Neves, Rogério I.; Mackley, Heath B.; Pameijer, Colette R.; Leung, Anna M.; Anderson, Bryan; Mallon, Carol; Robertson, Gavin P.; Drabick, Joseph J.

doi:10.1016/j.critrevonc.2016.04.010

Cited by 40 publications

(33 citation statements)

References 323 publications

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“…Given that ipilimumab is approved to be given concurrently with PD-1 inhibitors, it is feasible to explore the effect of adding radiotherapy to such a combination regimen. 33 A recent study showed that in both human and murine models, melanoma expressing high levels of PD-L1 did not respond to concurrent ipilimumab and radiotherapy. It was theorized that PD-L1 on melanoma cells allowed for an immune escape mechanism and that a combination of radiation, anti-CTLA-4, and anti PD-L1 could promote response and immunity through direct mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Improved survival and complete response rates in patients with advanced melanoma treated with concurrent ipilimumab and radiotherapy versus ipilimumab alone

Koller

Mackley

Liu

et al. 2016

Cancer Biology & Therapy

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136

105

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There is a growing body of evidence supporting the synergistic roles of radiotherapy and immunotherapy in the treatment of malignancy. Published case studies of the abscopal effect have been reported with the use of ipilimumab and radiotherapy in metastatic melanoma, but evidence supporting the routine use of this combination of therapy is limited. We conducted a retrospective analysis to evaluate patients treated with ipilimumab for advanced melanoma at a single institution from May 2011 to June 2015. Patients were grouped into those who had received concurrent radiotherapy while on ipilimumab (Ipi-RT), and those who did not. We then evaluated the treatment response following completion of ipilimumab. A total of 101 patients received ipilimumab in the prespecified time frame. 70 received Ipi-RT and 31 received ipilimumab without concurrent radiotherapy. Median overall survival (OS) was significantly increased in the concurrent Ipi-RT arm at 19 months vs. 10 months for ipilimumab alone (p = 0.01). Median progression free survival (PFS) was marginally increased in the Ipi-RT group compare with the ipilimumab alone group (5 months vs. 3 months, p = 0.20). Rates of complete response (CR) were significantly increased in the Ipi-RT group vs. ipilimumab alone (25.7% vs. 6.5%; p = 0.04), and rates of overall response (OR) in the groups were 37.1% vs. 19.4% (p = 0.11). No increase in toxicities was observed in the Ipi-RT group compare with ipilimumab alone. Prospective trials are needed to further clarify the role of radiotherapy with ipilimumab, but these encouraging preliminary observations suggest that this combination can induce more durable responses to immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Improved survival and complete response rates in patients with advanced melanoma treated with concurrent ipilimumab and radiotherapy versus ipilimumab alone

Koller

Mackley

Liu

et al. 2016

Cancer Biology & Therapy

Self Cite

136

105

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“…The idea of developing chemical treatments for cancer, or chemotherapies, was first explored in the early 20th century by the German chemistry Paul Ehrlich. 12,13,[97][98][99] Ehrlich theorized that chemical agents could target defined sub-populations of cells, and to this end he developed the first primitive alkylating agents. 12,13,[97][98][99] Ehrlich, incidentally, was also the first to suggest that immune cells were involved in eliminating transformed cells, though immune-based therapies would not be developed until the end of the 20th century.…”

Section: Chemotherapymentioning

confidence: 99%

“…12,13,[97][98][99] Ehrlich theorized that chemical agents could target defined sub-populations of cells, and to this end he developed the first primitive alkylating agents. 12,13,[97][98][99] Ehrlich, incidentally, was also the first to suggest that immune cells were involved in eliminating transformed cells, though immune-based therapies would not be developed until the end of the 20th century. 98 In 1910 George Clowes developed the first transplantable tumor system in rodents, which led to the development of model systems leading to a major breakthrough that allowed researchers and clinicians to screen prospective chemotherapeutic agents in a living organism.…”

Section: Chemotherapymentioning

confidence: 99%

Current state of melanoma diagnosis and treatment

Davis

Shalin

Tackett

2019

Cancer Biology & Therapy

640

463

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Melanoma is the deadliest form of skin cancer. In the early stages, melanoma can be treated successfully with surgery alone and survival rates are high, but after metastasis survival rates drop significantly. Therefore, early and correct diagnosis is key for ensuring patients have the best possible prognosis. Melanoma misdiagnosis accounts for more pathology and dermatology malpractice claims than any cancer other than breast cancer, as an early misdiagnosis can significantly reduce a patient’s chances of survival. As far as treatment for metastatic melanoma goes, there have been several new drugs developed over the last 10 years that have greatly improved the prognosis of patients with metastatic melanoma, however, a majority of patients do not show a lasting response to these treatments. Thus, new biomarkers and drug targets are needed to improve the accuracy of melanoma diagnosis and treatment. This article will discuss the major advancements of melanoma diagnosis and treatment from antiquity to the present day.

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“…To overcome or prevent drug resistance, immunotherapy has become promising therapeutic targets for cancer treatment. At present, immunotherapy has achieved satisfactory results in cancer treatment, such as malignant melanoma, but immunotherapy is not effective in the treatment of prostate cancer [27,28]. Alternatively, TIICs may be effective targets for drugs to improve clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%