Efficacy of anti-PD-1 and ipilimumab alone or in combination in acral melanoma
Background 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 there...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2022-07-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/10/7/e004668.full |
| _version_ | 1811323067178156032 |
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| author | Bart Neyns Lisa Zimmer Caroline Robert Celeste Lebbe Olivier Michielin Omid Hamid Anne Zaremba Oliver Klein Ruth Plummer Joanna Mangana Paolo A Ascierto Katharina C Kähler Georgina V Long Ryan Sullivan Grant A McArthur Michael Weichenthal Egle Ramelyte Meghan J Mooradian Douglas B Johnson Alexander Shoushtari Christian U Blank Judith M Versluis Prachi Bhave Claudia Trojanello Lu Si Inderjit Mehmi Tasnia Ahmed Alexander M Menzies Adnan Khattak Severine Roy Matteo S Carlino Paul C Lorigan Clara Allayous Rachel Roberts-Thomson Florentia Dimitriou Kathleen Batty Thierry Lesimple Serigne N Lo Alexandre Wicky Richard Heywood Lena Tran Anna Stansfeld Julia K Schwarze Andrea Maurichi Hui-Ling Yeoh Mario Santinami Andrew M Haydon |
| author_facet | Bart Neyns Lisa Zimmer Caroline Robert Celeste Lebbe Olivier Michielin Omid Hamid Anne Zaremba Oliver Klein Ruth Plummer Joanna Mangana Paolo A Ascierto Katharina C Kähler Georgina V Long Ryan Sullivan Grant A McArthur Michael Weichenthal Egle Ramelyte Meghan J Mooradian Douglas B Johnson Alexander Shoushtari Christian U Blank Judith M Versluis Prachi Bhave Claudia Trojanello Lu Si Inderjit Mehmi Tasnia Ahmed Alexander M Menzies Adnan Khattak Severine Roy Matteo S Carlino Paul C Lorigan Clara Allayous Rachel Roberts-Thomson Florentia Dimitriou Kathleen Batty Thierry Lesimple Serigne N Lo Alexandre Wicky Richard Heywood Lena Tran Anna Stansfeld Julia K Schwarze Andrea Maurichi Hui-Ling Yeoh Mario Santinami Andrew M Haydon |
| author_sort | Bart Neyns |
| collection | DOAJ |
| description | Background 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. |
| first_indexed | 2024-04-13T13:47:25Z |
| format | Article |
| id | doaj.art-0b1c2b670e1e4ec1b95b97b6b085c47b |
| institution | Directory Open Access Journal |
| issn | 2051-1426 |
| language | English |
| last_indexed | 2024-04-13T13:47:25Z |
| publishDate | 2022-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj.art-0b1c2b670e1e4ec1b95b97b6b085c47b2022-12-22T02:44:26ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262022-07-0110710.1136/jitc-2022-004668Efficacy of anti-PD-1 and ipilimumab alone or in combination in acral melanomaBart Neyns0Lisa Zimmer1Caroline Robert2Celeste Lebbe3Olivier Michielin4Omid Hamid5Anne Zaremba6Oliver Klein7Ruth Plummer8Joanna Mangana9Paolo A Ascierto10Katharina C Kähler11Georgina V Long12Ryan Sullivan13Grant A McArthur14Michael Weichenthal15Egle Ramelyte16Meghan J Mooradian17Douglas B Johnson18Alexander Shoushtari19Christian U Blank20Judith M Versluis21Prachi Bhave22Claudia Trojanello23Lu Si24Inderjit Mehmi25Tasnia Ahmed26Alexander M Menzies27Adnan Khattak28Severine Roy29Matteo S Carlino30Paul C Lorigan31Clara Allayous32Rachel Roberts-Thomson33Florentia Dimitriou34Kathleen Batty35Thierry Lesimple36Serigne N Lo37Alexandre Wicky38Richard Heywood39Lena Tran40Anna Stansfeld41Julia K Schwarze42Andrea Maurichi43Hui-Ling Yeoh44Mario Santinami45Andrew M Haydon461 Oncology, Universitair ziekenhuis Brussel, Brussel, BelgiumDepartment of Dermatology, University Hospital of Essen, Essen, GermanyDepartment of Medicine, Gustave Roussy Cancer Campus, Villejuif, FranceAP-HP Dermatology and CIC, INSERM U976, Saint Louis Hospital, Université de Paris, Paris, FranceDepartment of Oncology, Lausanne University Hospital, Lausanne, SwitzerlandCedars-Sinai Medical Center Angeles Clinic and Research Institute, Santa Monica, California, USAAff1 0000 0001 0262 7331grid.410718.bDepartment of DermatologyUniversity Hospital Essen Essen GermanyDepartment of Medical Oncology, Olivia Newton-John Cancer Centre, Austin Health, Melbourne, Victoria, AustraliaDepartment of Medical Oncology, Northern Centre for Cancer Care, Newcastle Hospitals NHS Trust and Newcastle University, Newcastle upon Tyne, UKDepartment of Dermatology, University Hospital Zurich, Zurich, SwitzerlandIstituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Campania, ItalyAff5 grid.412468.d0000000406462097Klinik für Dermatologie, Venerologie und AllergologieUniversitätsklinikum Schleswig-Holstein -Campus Kiel- Kiel GermanyMelanoma Institute Australia and University of Sydney, Sydney, New South Wales, AustraliaMassachusetts General Hospital Cancer Center, Boston, Massachusetts, USAResearch Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, AustraliaDepartment of Dermatology, University Hospital Schleswig-Holstein - Campus Kiel, Kiel, GermanyDepartment of Dermatology, University Hospital Zurich, Zurich, SwitzerlandMassachusetts General Hospital Cancer Center, Boston, Massachusetts, USADepartment of Medicine, Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, USADepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USANetherlands Cancer Institute, Amsterdam, The NetherlandsDepartment of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The NetherlandsDepartment of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, AustraliaUnit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Campania, ItalyKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Beijing, China11The Angeles Clinic and Research Institut, Los Angeles, CA, USAMelanoma Institute Australia, North Sydney, New South Wales, AustraliaMelanoma Institute Australia and University of Sydney, Sydney, New South Wales, AustraliaDepartment of Medical Oncology, Fiona Stanley Hospital, Murdoch, Western Australia, AustraliaGustave Roussy and Paris-Saclay University, Villejuif, FranceMelanoma Institute Australia and University of Sydney, Sydney, New South Wales, AustraliaThe Christie NHS Foundation Trust, Manchester, UKDepartment of Dermatology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, Île-de-France, FranceDivision of Cancer Medicine andMelanoma Institute Australia, North Sydney, New South Wales, AustraliaMedical Oncology, Royal North Shore Hospital, St Leonards, New South Wales, Australia12 Oncology, Centre Eugene Marquis, Rennes, FranceMelanoma Institute Australia, North Sydney, New South Wales, AustraliaOncology, Lausanne University Hospital, Lausanne, SwitzerlandChristie NHS Foundation Trust and Division of Cancer Services, University of Manchester, Manchester, UKMedicine, Vanderbilt University Medical Center, Nashville, Tennessee, USANorthern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne, UKMedical Oncology, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel, Brussel, BelgiumSurgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyMedical Oncology, Alfred Hospital, Melbourne, Victoria, AustraliaSurgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyMedical Oncology, Alfred Hospital, Melbourne, Victoria, AustraliaBackground 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.https://jitc.bmj.com/content/10/7/e004668.full |
| spellingShingle | Bart Neyns Lisa Zimmer Caroline Robert Celeste Lebbe Olivier Michielin Omid Hamid Anne Zaremba Oliver Klein Ruth Plummer Joanna Mangana Paolo A Ascierto Katharina C Kähler Georgina V Long Ryan Sullivan Grant A McArthur Michael Weichenthal Egle Ramelyte Meghan J Mooradian Douglas B Johnson Alexander Shoushtari Christian U Blank Judith M Versluis Prachi Bhave Claudia Trojanello Lu Si Inderjit Mehmi Tasnia Ahmed Alexander M Menzies Adnan Khattak Severine Roy Matteo S Carlino Paul C Lorigan Clara Allayous Rachel Roberts-Thomson Florentia Dimitriou Kathleen Batty Thierry Lesimple Serigne N Lo Alexandre Wicky Richard Heywood Lena Tran Anna Stansfeld Julia K Schwarze Andrea Maurichi Hui-Ling Yeoh Mario Santinami Andrew M Haydon Efficacy of anti-PD-1 and ipilimumab alone or in combination in acral melanoma Journal for ImmunoTherapy of Cancer |
| title | Efficacy of anti-PD-1 and ipilimumab alone or in combination in acral melanoma |
| title_full | Efficacy of anti-PD-1 and ipilimumab alone or in combination in acral melanoma |
| title_fullStr | Efficacy of anti-PD-1 and ipilimumab alone or in combination in acral melanoma |
| title_full_unstemmed | Efficacy of anti-PD-1 and ipilimumab alone or in combination in acral melanoma |
| title_short | Efficacy of anti-PD-1 and ipilimumab alone or in combination in acral melanoma |
| title_sort | efficacy of anti pd 1 and ipilimumab alone or in combination in acral melanoma |
| url | https://jitc.bmj.com/content/10/7/e004668.full |
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