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

• Authors: Zeynep Eroglu, Moffitt Cancer Center, Tampa; Kristy K Broman, Moffitt Cancer Center, Tampa; John F Thompson, Melanoma Institute Australia; Amanda Nijhuis, Melanoma Institute Australia; Tina J Hieken, Mayo Clinic, Rochester; Lisa Kottschade, Mayo Clinic, Rochester; Jeffrey M Farma, Fox Chase Cancer Center; Meghan Hotz, Fox Chase Cancer Center; Jeremiah Deneve, Univ Tennessee; Martin Fleming, Univ Tennessee; Edmund K Bartlett, Mem Sloan Kettering Canc Ctr; Avinash Sharma, Mem Sloan Kettering Canc Ctr; Lesly Dossett, University of Michigan; Tasha Hughes, University of Michigan; David E Gyorki, Peter MacCallum Cancer Centre; Jennifer Downs, Peter MacCallum Cancer Centre; Giorgos Karakousis, University of Pennsylvania; Yun Song, University of Pennsylvania; Ann Lee, New York University; Russell S Berman, New York University; Alexander van Akkooi, Netherlands Cancer Institute; Emma Stahlie, Netherlands Cancer Institute; Dale Han, Oregon Health and Science University; John Vetto, Oregon Health and Science University; Georgia Beasley, Duke University; Norma E Farrow, Duke University; Jane Yuet Chinga Hui, Univ Minnesota; Marc Moncrieff, Norfolk & Norwich University Hospital; Jenny Nobes, Norfolk & Norwich University Hospital; Kirsten Baecher, Emory University; Matthew Perez, Emory University; Michael Lowe, Emory University; David W Ollila, University of North Carolina; Frances A Collichio, University of North Carolina; Roger Olofsson Bagge, University of Gothenburg; Jan Mattsson, University of Gothenburg; Hidde M Kroon, University of Adelaide; Harvey Chai, University of Adelaide; Jyri Teras, North Estonia Medical Centre Foundation; James Sun, Moffitt Cancer Center, Tampa; Michael Carr, Emory University; Ankita Tandon, University of South Florida; Nalan Akgul Babacan, Moffitt Cancer Center, Tampa; Younchul Kim, Moffitt Cancer Center, Tampa; Mahrukh Naqvi, Moffitt Cancer Center, Tampa; Jonathan Zager, Moffitt Cancer Center, Tampa; Nikhil Khushalani, Moffitt Cancer Center, Tampa
• Journal Title: JOURNAL FOR IMMUNOTHERAPY OF CANCER
• Volume: Volume 10, Number 8
• Publisher: BMJ PUBLISHING GROUP | 2022-08-01
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1136/jitc-2021-004417
• Subjects: Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; Immunology; Melanoma; Adjuvants; Immunologic; STAGE-III; IPILIMUMAB; NIVOLUMAB

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.