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

Abstract

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.

Safety and efficacy of concurrent immune checkpoint inhibitors and hypofractionated body radiotherapy

“…[1][2][3][4][5][6][7][8][9][10][12][13][14][15][16][17][18][19][20][21]28 The few studies that have evaluated the combination of ICIs with RT have shown that these combinations are probably safe for conventional RT and brain stereotactic radiosurgery (SRS). [29][30][31][32][33][34][35][36] Evidence shows that hypofractionated RT (H-RT) is more immunogenic than conventional regimens [37][38][39] and may synergize better with ICIs. However, only a few patients in the reported combination studies received stereotactic ablative body RT (SAbR).…”

Microparticles from tumors exposed to radiation promote immune evasion in part by PD-L1

“…The finding that the distribution of PD-L1 expression is modified in response to radiation provides a rationale to combine radiation with immunomodulatory drugs, which is currently being evaluated in the clinical setting [16][17][18]. In this regard, in a prospective analysis of melanoma patients treated with CTLA-4 and radiation, a subset of patients benefited from the combinatorial therapy [42]. Furthermore, preclinical studies have indicated that the expression of PD-L1 on the cell surface of tumor cells is altered in response to radiation, thereby potentially contributing to the immunomodulation activity of radiotherapy [43,44].…”

Extracranial abscopal effect induced by combining immunotherapy with brain radiotherapy in a patient with lung adenocarcinoma: A case report and literature review

“…Immunotherapy can liberate and activate CD8+ T cells from an immunosuppressed state, thereby increasing the probability of abscopal effects . Reports of abscopal effects have increased along with the development of combined radiotherapy and immunotherapy, but these have mainly occurred in patients with highly immunogenic melanomas …”

“…7,8 Reports of abscopal effects have increased along with the development of combined radiotherapy and immunotherapy, but these have mainly occurred in patients with highly immunogenic melanomas. [9][10][11][12][13] The brain was previously considered an organ with immune privilege because it is difficult for nascent tumorassociated antigens to travel across the blood-brain barrier (BBB). 14 The occurrence of brain metastasis or the administration of radiation treatment often implies BBB opening.…”