TY - JOUR
T1 - Combined programmed cell death protein 1 and cytotoxic T-lymphocyte associated protein 4 blockade in an international cohort of patients with acral lentiginous melanoma
AU - Mcgillivray, Erin
AU - Ashouri, Karam
AU - Chatziioannou, Eftychia
AU - Gallegos, Jesus Antonio Ocejo
AU - Zarka, Jabra
AU - Kechter, Jacob
AU - Hwang, Angelina S.
AU - Zhang, Kevin
AU - Barros, Milton
AU - Yeh, Justin
AU - Okazaki, Ian
AU - Crocker, Andrew B.
AU - Maeda, Takuya
AU - Park, Soo J.
AU - Choi, Jacob
AU - Andreoli, Mia
AU - Darwish, Tarneem
AU - Savage, David J.
AU - Kim, Kevin B.
AU - Gupta, Jayant
AU - Shen, James
AU - Shirai, Keisuke
AU - Choi, April
AU - Pai, Lori
AU - Vazquez, Vinicius de Lima
AU - Moser, Justin
AU - Amaral, Teresa
AU - Aya, Leonel F. Hernandez
AU - Lutzky, Jose
AU - Najjar, Yana G.
AU - Costello, Collin M.
AU - Mangold, Aaron R.
AU - Bhatia, Shailender
AU - Gibney, Geoffrey T.
AU - Farma, Jeffrey M.
AU - Daniels, Gregory A.
AU - Sosman, Jeffrey
AU - Chandra, Sunandana
AU - Mangla, Ankit
AU - Bollin, Kathryn
AU - Possik, Patricia Abrao
AU - Robles-Espinoza, Carla Daniela
AU - Ito, Fumito
AU - In, Gino K.
N1 - © The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].
PY - 2024/12/10
Y1 - 2024/12/10
N2 - BACKGROUND: Combination immune checkpoint blockade targeting PD-1 and CTLA-4 leads to high response rates and improved survival in advanced cutaneous melanoma (CM). Less is known about the efficacy of this combination in acral lentiginous melanoma (ALM).OBJECTIVES: To determine the efficacy of combination immune checkpoint blockade targeting PD-1 and CTLA-4 in a real-world, diverse population of ALM.METHODS: This multi-institutional retrospective study analyzed patients with histologically confirmed ALM treated with the combination of PD-1 and CTLA-4 inhibitors between 2010-2022. The primary objective of the study was objective response rate (ORR) per RECIST criteria. The secondary objectives were progression-free survival (PFS) and overall survival (OS).RESULTS: In total, 109 patients with advanced ALM treated with combined PD-1 and CTLA-4 blockade in any line of treatment were included. The majority of patients had stage IV disease (n=81, 74.2%). The ORR for the entire cohort was 18.3% (95% CI 11.6-26.9%), with 9 (8.3%) complete responses (CR) and 11 (10.1%) partial responses (PR). An additional 22 patients (20.2%) had stable disease (SD), and the disease control rate (DCR) was 38.5%. The median PFS was 4.2 months [95% CI 3.25-5.62], while the median OS was 17 months [95% CI 12.4%-23.1%]. A total of 95 patients (87.2%) had a treatment-related adverse event, with 40.4% (n=44/109) experiencing at least one grade 3 or 4 toxicity. Elevated LDH (p=.04), 2+ lines of prior therapy (p=.03), and Asian race/ethnicity (p=.04) were associated with worse OS, while Hispanic/Latino race/ethnicity was associated with better OS (p=.02).CONCLUSIONS: Combination of PD-1 and CTLA-4 blockade is less effective for ALM, as compared to CM, despite similar toxicity. Asian patients, in particular, appear to derive lower benefit from this regimen. Novel treatment approaches are needed for this rare melanoma subtype.
AB - BACKGROUND: Combination immune checkpoint blockade targeting PD-1 and CTLA-4 leads to high response rates and improved survival in advanced cutaneous melanoma (CM). Less is known about the efficacy of this combination in acral lentiginous melanoma (ALM).OBJECTIVES: To determine the efficacy of combination immune checkpoint blockade targeting PD-1 and CTLA-4 in a real-world, diverse population of ALM.METHODS: This multi-institutional retrospective study analyzed patients with histologically confirmed ALM treated with the combination of PD-1 and CTLA-4 inhibitors between 2010-2022. The primary objective of the study was objective response rate (ORR) per RECIST criteria. The secondary objectives were progression-free survival (PFS) and overall survival (OS).RESULTS: In total, 109 patients with advanced ALM treated with combined PD-1 and CTLA-4 blockade in any line of treatment were included. The majority of patients had stage IV disease (n=81, 74.2%). The ORR for the entire cohort was 18.3% (95% CI 11.6-26.9%), with 9 (8.3%) complete responses (CR) and 11 (10.1%) partial responses (PR). An additional 22 patients (20.2%) had stable disease (SD), and the disease control rate (DCR) was 38.5%. The median PFS was 4.2 months [95% CI 3.25-5.62], while the median OS was 17 months [95% CI 12.4%-23.1%]. A total of 95 patients (87.2%) had a treatment-related adverse event, with 40.4% (n=44/109) experiencing at least one grade 3 or 4 toxicity. Elevated LDH (p=.04), 2+ lines of prior therapy (p=.03), and Asian race/ethnicity (p=.04) were associated with worse OS, while Hispanic/Latino race/ethnicity was associated with better OS (p=.02).CONCLUSIONS: Combination of PD-1 and CTLA-4 blockade is less effective for ALM, as compared to CM, despite similar toxicity. Asian patients, in particular, appear to derive lower benefit from this regimen. Novel treatment approaches are needed for this rare melanoma subtype.
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:001373537100001&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1093/bjd/ljae401
DO - 10.1093/bjd/ljae401
M3 - Article
C2 - 39438074
SN - 0007-0963
JO - British Journal of Dermatology
JF - British Journal of Dermatology
ER -