Neoadjuvant ipilimumab and nivolumab induces high pathologic response rates (pRRs) in clinical stage III nodal melanoma, and pathologic response is strongly associated with prolonged relapse-free survival (RFS). The PRADO extension cohort of the OpACIN-neo trial (NCT02977052) addressed the feasibility and effect on clinical outcome of using pathologic response after neoadjuvant ipilimumab and nivolumab as a criterion for further treatment personalization. In total, 99 patients with clinical stage IIIb–d nodal melanoma were included and treated with 6 weeks of neoadjuvant ipilimumab 1 mg kg⁻¹ and nivolumab 3 mg kg⁻¹. In patients achieving major pathologic response (MPR, ≤10% viable tumor) in their index lymph node (ILN, the largest lymph node metastasis at baseline), therapeutic lymph node dissection (TLND) and adjuvant therapy were omitted. Patients with pathologic partial response (pPR; >10 to ≤50% viable tumor) underwent TLND only, whereas patients with pathologic non-response (pNR; >50% viable tumor) underwent TLND and adjuvant systemic therapy ± synchronous radiotherapy. Primary objectives were confirmation of pRR (ILN, at week 6) of the winner neoadjuvant combination scheme identified in OpACIN-neo; to investigate whether TLND can be safely omitted in patients achieving MPR; and to investigate whether RFS at 24 months can be improved for patients achieving pNR. ILN resection and ILN-response-tailored treatment were feasible. The pRR was 72%, including 61% MPR. Grade 3–4 toxicity within the first 12 weeks was observed in 22 (22%) patients. TLND was omitted in 59 of 60 patients with MPR, resulting in significantly lower surgical morbidity and better quality of life. The 24-month relapse-free survival and distant metastasis-free survival rates were 93% and 98% in patients with MPR, 64% and 64% in patients with pPR, and 71% and 76% in patients with pNR, respectively. These findings provide a strong rationale for randomized clinical trials testing response-directed treatment personalization after neoadjuvant ipilimumab and nivolumab.

新辅助伊匹单抗和纳武单抗在临床 III 期淋巴结黑色素瘤中诱导高病理缓解率 (pRR)，并且病理缓解与延长无复发生存期 (RFS) 密切相关。 OpACIN-neo 试验 (NCT02977052) 的 PRADO 扩展队列探讨了使用新辅助伊匹单抗和纳武单抗后的病理反应作为进一步个性化治疗的标准的可行性及其对临床结果的影响。总共纳入了 99 名临床 IIIb-d 期淋巴结黑色素瘤患者，并接受新辅助伊匹单抗 1 mg kg ^-1和纳武单抗 3 mg kg ^-1治疗 6 周。在指数淋巴结（ILN，基线时最大的淋巴结转移）达到主要病理缓解（MPR，≤10% 活肿瘤）的患者中，省略治疗性淋巴结清扫术（TLND）和辅助治疗。病理部分缓解（pPR；>10%至≤50%活肿瘤）的患者仅接受TLND，而病理无反应（pNR；>50%活肿瘤）患者接受TLND和辅助全身治疗±同步放疗。主要目标是确认 OpACIN-neo 中确定的获胜新辅助组合方案的 pRR（ILN，第 6 周）；研究在实现 MPR 的患者中是否可以安全地省略 TLND；并研究是否可以改善达到 pNR 的患者 24 个月时的 RFS。 ILN 切除和 ILN 反应定制治疗是可行的。 pRR 为 72%，其中 MPR 为 61%。 22 名 (22%) 患者在前 12 周内观察到 3-4 级毒性。 60 名 MPR 患者中有 59 名省略了 TLND，从而显着降低了手术发病率并提高了生活质量。 MPR患者的24个月无复发生存率和无远处转移生存率分别为93%和98%，pPR患者为64%和64%，pNR患者为71%和76%。这些发现为测试新辅助伊匹单抗和纳武单抗后的反应导向治疗个性化的随机临床试验提供了强有力的理由。