Outcomes with adjuvant anti-PD-1 therapy in patients with sentinel lymph node-positive melanoma without completion lymph node dissection

Abstract

Until recently, most patients with sentinel lymph node-positive (SLN+) melanoma underwent a completion lymph node dissection (CLND), as mandated in published trials of adjuvant systemic therapies. Following multicenter selective lymphadenectomy trial-II, most patients with SLN+ melanoma no longer undergo a CLND prior to adjuvant systemic therapy. A retrospective analysis of clinical outcomes in SLN+ melanoma patients treated with adjuvant systemic therapy after July 2017 was performed in 21 international cancer centers. Of 462 patients who received systemic adjuvant therapy, 326 patients received adjuvant anti-PD-1 without prior immediate (IM) CLND, while 60 underwent IM CLND. With median follow-up of 21 months, 24-month relapse-free survival (RFS) was 67% (95% CI 62% to 73%) in the 326 patients. When the patient subgroups who would have been eligible for the two adjuvant anti-PD-1 clinical trials mandating IM CLND were analyzed separately, 24-month RFS rates were 64%, very similar to the RFS rates from those studies. Of these no-CLND patients, those with SLN tumor deposit >1 mm, stage IIIC/D and ulcerated primary had worse RFS. Of the patients who relapsed on adjuvant anti-PD-1, those without IM CLND had a higher rate of relapse in the regional nodal basin than those with IM CLND (46% vs 11%). Therefore, 55% of patients who relapsed without prior CLND underwent surgery including therapeutic lymph node dissection (TLND), with 30% relapsing a second time; there was no difference in subsequent relapse between patients who received observation vs secondary adjuvant therapy. Despite the increased frequency of nodal relapses, adjuvant anti-PD-1 therapy may be as effective in SLN+ pts who forego IM CLND and salvage surgery with TLND at relapse may be a viable option for these patients.

Keywords: Adjuvants, Immunologic; Melanoma.

Figure 1

(A) RFS and (B) OS in SLN+ melanoma with adjuvant anti-PD-1 therapy in patient with no immediate CLND (n=326). CLND, completion lymph node dissection; IM, immediate; OS, overall survival; RFS, relapse-free survival; SLN+, sentinel lymph node-positive.

Figure 2

Relapse-free survival between different baseline characteristics. In the 326 patients without CLND treated with adjuvant anti-PD-1, RFS based on ulcerated primary (A), stage (B), head/neck primary (C), number of positive SLN (D), extranodal extension (E), and SLN tumor deposit (F) is shown. CLND, completion lymph node dissection; RFS, relapse-free survival; SLN, sentinel lymph node.

Figure 3

Patterns of relapse and postrelapse treatments in patients. (A) *11 patients with regional nodal Basin relapse had concurrent intransit/satellite relapse *9 patients with distant relapse had concurrent nodal relapse. (B) *One patient with distant relapse had concurrent nodal relapse and two had concurrent in-transit relapse. (C) *5 of 44 patients with relapse without further surgery or drug therapy—1 intralesional therapy, 1 radiation only, 1 unknown treatment—3 of 5 decreased. Of 39 patients, 3 enrolled in clinical trials (anti-PD-1 with intralesional therapy). #2 of 33 with chemotherapy or unknown systemic treatment. CLND, completion lymph node dissection; IM, immediate; TLND, therapeutic lymph node dissection; XRT, radiation therapy.