Exceptional responses with sequential metronomic temozolomide after pembrolizumab failure in patients with metastatic melanoma. Issue 6 (December 2019)

• Record Type: Journal Article
• Authors: Swami, Umang; Monga, Varun; Freesmeier, Michele; Zhang, Weizhou; Bossler, Aaron D.; Zakharia, Yousef; Milhem, Mohammed
• Is Part Of: Melanoma research. Volume 29:Issue 6(2019)
• Publication Date: 2019-12
• Subjects: immunomodulation -- immunotherapy resistance -- metastatic melanoma -- pembrolizumab -- regulatory T cells -- temozolomide; Melanoma -- Periodicals; Melanoma -- Periodicals; Melanomen; 616.99477
• DOI: 10.1097/CMR.0000000000000592
• Languages: English
• ISSNs: 0960-8931

Abstract

Abstract : Pembrolizumab is an effective therapy for 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 Treg population can also decrease significantly. Herein, we present a case series of three patients with metastatic melanoma who after progression on pembrolizumab showed a radiological response after just one 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.