Efficacy of anti-PD-1 and ipilimumab alone or in combination in acral melanoma
Lo, S. N.
Versluis, J. M.
Schwarze, J. K.
Mooradian, M. J.
Yeoh, H. L.
Blank, C. U.
Kähler, K. C.
Ascierto, P. A.
Lorigan, Paul C
Johnson, D. B.
McArthur, G. A.
Haydon, A. M.
Long, G. V.
Menzies, A. M.
Carlino, M. S.
AffiliationSir Peter MacCallum Cancer Centre Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
MetadataShow full item record
AbstractBackground: Acral melanoma is a rare melanoma subtype with poor prognosis. Importantly, these patients were not identified as a specific subgroup in the landmark melanoma trials involving ipilimumab and the anti-programmed cell death protein-1 (PD-1) agents nivolumab and pembrolizumab. There is therefore an absence of prospective clinical trial evidence regarding the efficacy of checkpoint inhibitors (CPIs) in this population. Acral melanoma has lower tumor mutation burden (TMB) than other cutaneous sites, and primary site is associated with differences in TMB. However the impact of this on the effectiveness of immune CPIs is unknown. We examined the efficacy of CPIs in acral melanoma, including by primary site. Methods: Patients with unresectable stage III/IV acral melanoma treated with CPI (anti-PD-1 and/or ipilimumab) were studied. Multivariable logistic and Cox regression analyses were conducted. Primary outcome was objective response rate (ORR); secondary outcomes were progression-free survival (PFS) and overall survival (OS). Results: In total, 325 patients were included: 234 (72%) plantar, 69 (21%) subungual and 22 (7%) palmar primary sites. First CPI included: 184 (57%) anti-PD-1, 59 (18%) anti-PD-1/ipilimumab combination and 82 (25%) ipilimumab. ORR was significantly higher with initial anti-PD-1/ipilimumab compared with anti-PD-1 (43% vs 26%, HR 2.14, p=0.0004) and significantly lower with ipilimumab (15% vs 26%, HR 0.49, p=0.0016). Landmark PFS at 1 year was highest for anti-PD-1/ipilimumab at 34% (95% CI 24% to 49%), compared with 26% (95% CI 20% to 33%) with anti-PD-1 and 10% (95% CI 5% to 19%) with ipilimumab. Despite a trend for increased PFS, anti-PD-1/ipilimumab combination did not significantly improve PFS (HR 0.85, p=0.35) or OS over anti-PD-1 (HR 1.30, p=0.16), potentially due to subsequent therapies and high rates of acquired resistance. No outcome differences were found between primary sites. Conclusion: While the ORR to anti-PD-1/ipilimumab was significantly higher than anti-PD-1 and PFS numerically higher, in this retrospective cohort this benefit did not translate to improved OS. Future trials should specifically include patients with acral melanoma, to help determine the optimal management of this important melanoma subtype.
CitationBhave P, Ahmed T, Lo SN, Shoushtari A, Zaremba A, Versluis JM, et al. Efficacy of anti-PD-1 and ipilimumab alone or in combination in acral melanoma. Journal for immunotherapy of cancer. 2022 Jul;10(7). PubMed PMID: 35793872. Pubmed Central PMCID: PMC9260790. Epub 2022/07/07. eng.
JournalJournal for Immunotherapy of Cancer
- Biologic subtypes of melanoma predict survival benefit of combination anti-PD1+anti-CTLA4 immune checkpoint inhibitors versus anti-PD1 monotherapy.
- Authors: Rose AAN, Armstrong SM, Hogg D, Butler MO, Saibil SD, Arteaga DP, Pimentel Muniz T, Kelly D, Ghazarian D, King I, Kamil ZS, Ross K, Spreafico A
- Issue date: 2021 Jan
- Efficacy and safety of anti-PD-1 and anti-PD-1 combined with anti-CTLA-4 immunotherapy to advanced melanoma: A systematic review and meta-analysis of randomized controlled trials.
- Authors: Hao C, Tian J, Liu H, Li F, Niu H, Zhu B
- Issue date: 2017 Jun
- MAPKinase inhibition after failure of immune checkpoint blockade in patients with advanced melanoma - An evaluation of the multicenter prospective skin cancer registry ADOREG.
- Authors: Kreft S, Glutsch V, Zaremba A, Schummer P, Mohr P, Grimmelmann I, Gutzmer R, Meier F, Pföhler C, Sachse MM, Meiss F, Forschner A, Haferkamp S, Welzel J, Terheyden P, Herbst R, Utikal J, Kaatz M, Weishaupt C, Kreuter A, Debus D, Duecker P, Sindrilaru A, Löffler H, Schley G, Weichenthal M, Schadendorf D, Ugurel S, Gesierich A, Schilling B
- Issue date: 2022 May
- Single-agent anti-PD-1 or combined with ipilimumab in patients with mucosal melanoma: an international, retrospective, cohort study.
- Authors: Dimitriou F, Namikawa K, Reijers ILM, Buchbinder EI, Soon JA, Zaremba A, Teterycz P, Mooradian MJ, Armstrong E, Nakamura Y, Vitale MG, Tran LE, Bai X, Allayous C, Provent-Roy S, Indini A, Bhave P, Farid M, Kähler KC, Mehmi I, Atkinson V, Klein O, Stonesifer CJ, Zaman F, Haydon A, Carvajal RD, Hamid O, Dummer R, Hauschild A, Carlino MS, Mandala M, Robert C, Lebbe C, Guo J, Johnson DB, Ascierto PA, Shoushtari AN, Sullivan RJ, Cybulska-Stopa B, Rutkowski P, Zimmer L, Sandhu S, Blank CU, Lo SN, Menzies AM, Long GV
- Issue date: 2022 Sep
- Response to immune checkpoint inhibitors in acral melanoma: A nationwide cohort study.
- Authors: van Not OJ, de Meza MM, van den Eertwegh AJM, Haanen JB, Blank CU, Aarts MJB, van den Berkmortel FWPJ, van Breeschoten J, de Groot JB, Hospers GAP, Ismail RK, Kapiteijn E, Piersma D, van Rijn RS, Stevense-den Boer MAM, van der Veldt AAM, Vreugdenhil G, Bonenkamp HJ, Boers-Sonderen MJ, Blokx WAM, Wouters MWJM, Suijkerbuijk KPM
- Issue date: 2022 May