Glutsch Valerie, Schummer Patrick, Goebeler Matthias, Gesierich Anja, Schilling Bastian
Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany.
Department of Dermatology, University Hospital, Goethe University Frankfurt, Frankfurt, Germany.
Front Immunol. 2024 Dec 5;15:1495004. doi: 10.3389/fimmu.2024.1495004. eCollection 2024.
Merkel cell carcinoma (MCC) is a rare but highly aggressive cutaneous malignancy. Immune checkpoint inhibition (ICI) with PD-(L)1 blockade has significantly improved treatment outcomes in metastatic disease. In patients with primary resistance to PD-(L)1 inhibition, a high overall response rate (ORR) of 50% to later-line ipilimumab plus nivolumab (IPI/NIVO) has been demonstrated. However, clinical data on patients with progression after an initial response to IPI/NIVO are still lacking.
Clinical data of three metastatic MCC patients who were re-exposed to IPI/NIVO after progression were retrospectively evaluated.
Two of the three patients showed primary resistance to avelumab with progressive disease, while one patient showed complete response (according to RECIST V.1.1). All three patients received combined ICI with IPI/NIVO as subsequent therapy, resulting in an ORR of ∼ 67%. However, all three patients progressed during follow-up and were re-exposed to IPI/NIVO. With a follow-up period ranging from 6.5 to 37.1 months, no PFS event has been detected. ORR for IPI/NIVO re-exposition was equal to that of initial IPI/NIVO treatment.
In this retrospective follow-up analysis, we observed a response rate of 67% and long-lasting responses after re-exposition to combined ICI in metastatic MCC patients with progression after initial response or disease control upon their first IPI/NIVO treatment. An important observation from this small analysis is that primary resistance to PD-L1 inhibition may result in a better response to IPI/NIVO.
默克尔细胞癌（MCC）是一种罕见但侵袭性很强的皮肤恶性肿瘤。使用程序性死亡受体 1（PD-1）/程序性死亡配体 1（PD-L1）阻断剂进行免疫检查点抑制（ICI）显著改善了转移性疾病的治疗效果。在对 PD-(L)1 抑制产生原发性耐药的患者中，已证明二线使用伊匹单抗加纳武单抗（IPI/NIVO）的总体缓解率（ORR）高达 50%。然而，关于在首次使用 IPI/NIVO 治疗后出现疾病进展的患者的临床数据仍然缺乏。
回顾性评估了 3 例转移性 MCC 患者在疾病进展后再次接受 IPI/NIVO 治疗的临床数据。
3 例患者中有 2 例对阿维鲁单抗原发性耐药且疾病进展，而 1 例患者出现完全缓解（根据实体瘤疗效评价标准第 1.1 版）。所有 3 例患者均接受了 IPI/NIVO 联合 ICI 作为后续治疗，ORR 约为 67%。然而，所有 3 例患者在随访期间均出现疾病进展，并再次接受 IPI/NIVO 治疗。随访期为 6.5 至 37.1 个月，未检测到无进展生存期（PFS）事件。再次使用 IPI/NIVO 的 ORR 与首次使用 IPI/NIVO 治疗时相同。
在这项回顾性随访分析中，我们观察到在首次 IPI/NIVO 治疗后出现疾病进展或疾病得到控制的转移性 MCC 患者中，再次接受联合 ICI 治疗的缓解率为 67%，且缓解持续时间较长。这项小型分析的一个重要发现是，对 PD-L1 抑制的原发性耐药可能导致对 IPI/NIVO 有更好的反应。
