Nova Southeastern University Dr Kiran C Patel College of Allopathic Medicine, Davie, Florida, USA.
Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida, USA.
J Immunother Cancer. 2024 Sep 5;12(9):e009816. doi: 10.1136/jitc-2024-009816.
Advanced Merkel cell carcinoma (MCC) has a high response rate to immune checkpoint blockade (ICB) therapy, but the durability of responses once treatment is discontinued remains unclear. We therefore reviewed the long-term outcomes of advanced patients with MCC who discontinued ICB treatment after achieving favorable initial response.
We performed a retrospective review of advanced patients with MCC treated at a single high-volume referral center, including all patients who received at least one dose of anti-programmed death receptor 1 (ligand) monotherapy for unresectable or metastatic disease, achieved stable disease (SD) or better, and discontinued treatment for a reason other than disease progression.
Of 195 advanced patients with MCC treated with ICB, we identified 45 who met the study criteria. Of these, 21 (46.6%) had a complete response (CR) to initial ICB treatment, 23 (51.1%) a partial response and 1 (2.2%) SD. 25 (55.6%) patients discontinued ICB electively and 20 (44.4%) discontinued due to toxicity. In total, 21 of the 45 patients (46.6%) experienced disease progression at a median of 11.3 months (range 2.1-22.7 months) from ICB cessation. There was a lower rate of progression in patients who achieved CR versus non-CR (23.8% vs 66.7%, p=0.006) and a trend towards a lower rate in those who discontinued electively versus due to toxicity (36.0% vs 60.0%, p=0.14). There was a higher risk for progression in patients with viral positive MCC compared with viral negative MCC (75.0 vs 30.8%, p=0.02). 16 of the 21 patients who experienced progression were retreated subsequently with ICB therapy, including both single-agent rechallenge (12) and escalation to combination ICB (4). 11 of 15 evaluable ICB-retreated patients (73.3%) achieved an objective response.
Patients with advanced MCC have a substantial risk of disease progression following treatment discontinuation despite initial favorable ICB response, particularly in those that achieve less than a CR. Most of these patients maintain sensitivity to retreatment with the same drug class. Virus-positive MCC may be a risk factor for post-discontinuation relapse, which should be validated in future studies.
高级 Merkel 细胞癌 (MCC) 对免疫检查点阻断 (ICB) 治疗有很高的反应率，但停药后反应的持久性尚不清楚。因此，我们回顾了在获得初始有利反应后停止 ICB 治疗的晚期 MCC 患者的长期结果。
我们对一家高容量转诊中心治疗的晚期 MCC 患者进行了回顾性分析，包括所有接受至少一剂抗程序性死亡受体 1（配体）单药治疗不可切除或转移性疾病、达到稳定疾病 (SD) 或更好、并因疾病进展以外的原因停止治疗的患者。
在接受 ICB 治疗的 195 例晚期 MCC 患者中，我们确定了符合研究标准的 45 例。其中，21 例（46.6%）对初始 ICB 治疗有完全缓解 (CR)，23 例（51.1%）有部分缓解，1 例（2.2%）有 SD。25 例（55.6%）患者自愿停止 ICB 治疗，20 例（44.4%）因毒性停止治疗。总的来说，45 例患者中有 21 例（46.6%）在停止 ICB 后 11.3 个月（范围 2.1-22.7 个月）中位数时出现疾病进展。与非 CR 相比，CR 患者的进展率较低（23.8% vs 66.7%，p=0.006），与因毒性而停止治疗相比，这一趋势更低（36.0% vs 60.0%，p=0.14）。与病毒阴性 MCC 相比，病毒阳性 MCC 患者的进展风险更高（75.0% vs 30.8%，p=0.02）。21 例进展患者中有 16 例随后接受 ICB 治疗，包括单药再挑战（12 例）和联合 ICB 升级（4 例）。15 例可评估的 ICB 再治疗患者中有 11 例（73.3%）获得客观缓解。
尽管初始 ICB 反应良好，但接受治疗的晚期 MCC 患者停药后仍有很大的疾病进展风险，尤其是那些未达到 CR 的患者。这些患者中的大多数对同种药物类别的再治疗仍保持敏感性。病毒阳性 MCC 可能是停药后复发的一个危险因素，这需要在未来的研究中得到验证。
