Quinnipiac University Frank H Netter MD School of Medicine, North Haven, Connecticut, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
J Immunother Cancer. 2024 Aug 28;12(8):e009061. doi: 10.1136/jitc-2024-009061.
The combination of ipilimumab and nivolumab is a highly effective treatment for metastatic cutaneous melanoma. However, immune-related adverse events (irAEs) are common, often necessitating treatment interruption and the use of immunosuppressive agents. There is no data on the impact of resuming nivolumab on survival following recovery from the irAE and completion of immunosuppressive treatment.
In this retrospective analysis, we examined a cohort of patients treated with ipilimumab/nivolumab who developed irAEs requiring treatment interruption and immunosuppressive therapy. The differences in physician practice patterns at our institution allowed us to examine the survival effect of restarting single-agent nivolumab. A multivariate analysis of clinical factors associated with improved survival was performed.
We identified 165 patients who were treated with ipilimumab/nivolumab and developed irAEs requiring treatment interruption and immunosuppressive therapy. Patients with the best overall response of progressive disease were excluded. Of the remaining 122 patients, 46 resumed single-agent nivolumab. When stratified by age and adjusted for sex, M-stage, lactate dehydrogenase (LDH), therapy duration, and irAE type, the effect of resumption of nivolumab on survival was highly significant (p=0.02). Patients who resumed nivolumab had a 68% reduction in the hazard of death compared with patients who had not yet or never resumed nivolumab (HR: 0.32, 95% CI: 0.12 to 0.84). Of the patients who resumed nivolumab, 12 (26%) patients had subsequent irAEs, with five patients having grade 3 irAEs. No grade 4 or 5 irAEs were noted.
Resuming single-agent nivolumab following a treatment interruption for ipilimumab/nivolumab-associated irAE and completion of immunosuppressive therapy increased overall survival compared with discontinuing nivolumab permanently in patients with metastatic melanoma. Toxicity observed post-resumption of single-agent nivolumab was manageable with no severe irAEs observed.
伊匹单抗和纳武单抗联合治疗转移性皮肤黑色素瘤的疗效显著。然而，免疫相关不良事件（irAEs）较为常见，常需中断治疗并使用免疫抑制剂。irAE 缓解且免疫抑制治疗结束后重新使用纳武单抗对生存的影响尚无数据。
本回顾性分析纳入了接受伊匹单抗/纳武单抗治疗后发生需要中断治疗和免疫抑制治疗的 irAEs 的患者队列。本研究机构的医生实践模式存在差异，因此我们可以检查重新使用单药纳武单抗的生存效果。对与生存改善相关的临床因素进行了多变量分析。
我们确定了 165 例接受伊匹单抗/纳武单抗治疗并发生需要中断治疗和免疫抑制治疗的 irAEs 的患者。排除了总体缓解为进展性疾病的患者。在剩余的 122 例患者中，46 例重新使用了单药纳武单抗。按年龄分层，并根据性别、M 分期、乳酸脱氢酶（LDH）、治疗持续时间和 irAE 类型进行调整后，重新使用纳武单抗对生存的影响具有统计学显著性（p=0.02）。与未重新使用或从未重新使用纳武单抗的患者相比，重新使用纳武单抗的患者死亡风险降低了 68%（风险比：0.32，95%置信区间：0.12 至 0.84）。重新使用纳武单抗的患者中有 12 例（26%）出现了后续 irAEs，其中 5 例为 3 级 irAEs。未观察到 4 级或 5 级 irAEs。
在接受伊匹单抗/纳武单抗相关 irAE 治疗中断和免疫抑制治疗完成后重新使用单药纳武单抗可提高转移性黑色素瘤患者的总体生存，与永久停用纳武单抗相比。重新使用单药纳武单抗后观察到的毒性是可以控制的，未观察到严重的 irAEs。
