Dacarbazine (DTIC) and its oral counterpart temozolomide (TMZ) have been the most used agents in advanced malignant melanoma (MM) patients and they are still used routinely. The preferred first line treatment, immune checkpoint inhibitors (CPIs) might shape the tumor and the tumor microenvironment, possibly affecting the response to subsequent therapies. The aim of this study was to investigate the treatment effect of DTIC/TMZ in MM patients after CPI therapy in a consecutive patient cohort and through systematic literature review and meta-analysis. Thirty-five patients with advanced MM treated with DTIC/TMZ after previous CPI therapy in three Swedish regions between 2017 and 2021 were recognized and seven case series studies were identified through systematic database review. Pooled data from all 345 patients showed a median real-world progression-free survival (rwPFS) of 1.9 months and overall survival (OS) of 6.0 months. Three of these studies were included in a meta-analysis comparing DTIC/TMZ after CPI treatment, versus no previous immunotherapy, showing no statistically significant differences in rwPFS or OS but higher real-world response rate to chemotherapy for the prior-CPI treated group (Odds Ratio: 2.24; 95% Confidence Interval: 1.04–4.86). The current study supports consideration of DTIC/TMZ in later line of treatment in the immunotherapy era.

中文翻译：

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恶性黑色素瘤患者接受免疫检查点抑制剂治疗后达卡巴嗪和替莫唑胺治疗的作用：病例系列和荟萃分析

达卡巴嗪 (DTIC) 及其口服对应物替莫唑胺 (TMZ) 是晚期恶性黑色素瘤 (MM) 患者最常用的药物，并且仍然常规使用。作为首选的一线治疗，免疫检查点抑制剂（CPI）可能会塑造肿瘤和肿瘤微环境，可能会影响对后续治疗的反应。本研究的目的是通过系统文献回顾和荟萃分析，通过连续患者队列研究 CPI 治疗后 DTIC/TMZ 对 MM 患者的治疗效果。2017 年至 2021 年间，瑞典三个地区有 35 名接受过 CPI 治疗后接受 DTIC/TMZ 治疗的晚期 MM 患者得到认可，并通过系统数据库审查确定了 7 个病例系列研究。所有 345 名患者的汇总数据显示，真实世界中位无进展生存期 (rwPFS) 为 1.9 个月，总生存期 (OS) 为 6.0 个月。其中三项研究被纳入荟萃分析中，比较 CPI 治疗后的 DTIC/TMZ 与既往未接受免疫治疗的情况，显示 rwPFS 或 OS 没有统计学上的显着差异，但先前 CPI 治疗组对化疗的实际反应率较高（比值比：2.24；95% 置信区间：1.04–4.86)。目前的研究支持在免疫治疗时代的后期治疗中考虑 DTIC/TMZ。