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Exceptional responses with sequential metronomic temozolomide after pembrolizumab failure in patients with metastatic melanoma
Journal article   Peer reviewed

Exceptional responses with sequential metronomic temozolomide after pembrolizumab failure in patients with metastatic melanoma

Umang Swami, Varun Monga, Michele Freesmeier, Weizhou Zhang, Aaron D Bossler, Yousef Zakharia and Mohammed Milhem
Melanoma research, Vol.29(6), pp.643-647
12/2019
DOI: 10.1097/CMR.0000000000000592
PMID: 30829928

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Abstract

Pembrolizumab is an effective therapy in patients with metastatic melanoma. However, not all patients derive benefit. It is postulated that an increase in regulatory T cells in melanoma patients can impair the response to immunotherapies. Continuous low dose temozolomide has shown to cause immunomodulatory effects resulting in CD4+ lymphopenia due to which T-reg population can also decrease significantly. Herein we present a case series of 3 patients with metastatic melanoma who after progression on pembrolizumab showed a radiological response after just 1 cycle of metronomic temozolomide (75 mg/m 2 daily for 6 weeks on 8-week cycle). This suggests that temozolomide may be a useful alternative for patients with metastatic melanoma after disease progression on pembrolizumab. Further studies with biomarkers are warranted to elucidate which patients will derive benefit from this strategy.
Immunomodulation immunotherapy resistance metastatic melanoma pembrolizumab regulatory T cells temozolomide

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