Racial and ethnic representation across acral lentiginous melanoma clinical trials

doi:10.21203/rs.3.rs-8097218/v1

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Racial and ethnic representation across acral lentiginous melanoma clinical trials

https://doi.org/10.21203/rs.3.rs-8097218/v1

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Acral lentiginous melanoma (ALM) is a rare form of cutaneous melanoma (CM) affecting the palm, soles and nailbeds. ALM predominantly affects people with skin of color, and it is the most common form of CM diagnosed in Black populations. Globally, ALM is the predominant CM subtype diagnosed in certain Asian and Latin American countries. Thus, it is imperative that ALM clinical trials reflect the diversity of participants affected. The purpose of this study is to assess racial and ethnic representation in Phase I-IV clinical trials for ALM using The U.S. National Library of Medicine clinical trials database and PubMed. 11 clinical trials with 394 participants were included in our analysis. Nine clinical trials included other melanoma subtypes, as, 39.6% of participants were diagnosed with ALM, 39.3% with mucosal melanoma, and 16.5% with other subtypes or skin conditions. Six clinical trials reported race and ethnicity, and we found that 79.4% of the participants were White, 15.9% were Asian, 3.2% were Black, and 0.5% were reported as more than one race. Only three studies reported ethnicity, in which only 11.30% of participants were Hispanic. Compared to the U.S. Census Bureau and a previously published Surveillance, Epidemiology, and End Results study, White participants were overall highly represented, and racial and ethnic minority participants were underrepresented. Our findings highlight the need for the systematic inclusion of racial and ethnic minority groups and improved demographic reporting in ALM clinical trials.

Acral lentiginous melanoma

clinical trials

diversity

race

and ethnicity

Acral lentiginous melanoma (ALM) is a rare and aggressive subtype of cutaneous melanoma (CM) that occurs on the palms, soles, and nails, accounting for only 2–3% of melanoma cases [4]. Unlike other subtypes of CM, which predominantly affect non-Hispanic White populations, ALM mainly affects people with skin of color. In the United States, ALM is the most common form of CM diagnosed in Black individuals [3]. Globally, ALM is the most frequently diagnosed form of melanoma in Asian countries, such as Singapore, Japan, China, and Taiwan [2]. In Latin America, the prevalence of ALM varies depending on the ancestral composition of specific countries. However, ALM comprises most melanoma diagnoses in countries such as Mexico and Peru [2].

Most clinical trials used to inform treatment guidelines are either based on other CM subtypes or include ALM only as a subset, rather than being specifically for ALM [5]. Furthermore, given the racial and ethnic diversity of individuals diagnosed with ALM, clinical trial participants must reflect this diversity. Increasing the inclusion of ALM and historically underrepresented groups will significantly improve the generalizability of results, ensuring that the benefits and risk profiles of therapies are reflective of all melanoma subtypes and diverse populations. Here, we aimed to evaluate the racial and ethnic representation in global clinical trials for ALM.

We identified Phase I-IV clinical trials published after 2000 using The U.S. National Library of Medicine clinical trials database (clinicaltrials.gov) and PubMed on September 24, 2025. We used the search term “Acral Lentiginous Melanoma” in both databases and excluded studies that are actively recruiting participants, did not have a completed status, corresponding publication, or available results. Additionally, we only included trials that specified the number of participants with ALM. On PubMed, we filtered articles to include those classified as “Clinical Trial”.

When reporting racial and ethnic diversity across studies, the denominator was based on studies that reported race and ethnicity. Racial and ethnic data were reported using definitions from the U.S. Census Bureau. To compare participant demographics for studies conducted in the United States to racial and ethnic diversity in the country, we compared racial and ethnic representation to the U.S. Census Bureau population estimates from July 1, 2024 [7]. We also identified differences in clinical trial diversity from ALM demographics as reported by a previously published Surveillance, Epidemiology, and End Results (SEER) study, which included ALM cases diagnosed from 2006–2015 and reported in 18 population-based registries [6].

11 clinical trials resulting in a total of 394 participants were included in our analysis. Six trials were conducted in the United States; two were conducted in China, and one in Japan. Nine of our included trials included other melanoma subtypes. 39.6% of participants (n = 156) were diagnosed with acral lentiginous melanoma, 39.3% with mucosal melanoma (n = 155), and 16.5% were diagnosed with other subtypes or skin conditions, including chronic-sun damage (n = 24), ocular melanoma (n = 4), melanoma of the soft part (n = 1), or other subtypes of cutaneous melanoma (n = 36).

Six of these clinical trials with a total of 189 participants reported race and ethnicity (Table 1). In these studies that reported race, 79.4% of the participants were White (n = 150), 3.2% were Black (n = 6), 15.9% were Asian (n = 30), and 0.5% were reported as more than one race (n = 1). Only three studies reported ethnicity (n = 71), in which only 11.30% of participants were Hispanic (n = 8).

Table 1
Title: Racial and ethnic representation in clinical trials reporting race and ethnicity demographics
Race and Ethnicity	Percentage of participants across clinical trials (n = 189)
White	79.4% (150)
Black	3.2% (6)
Asian	15.9% (30)
Two or more races	0.5% (1)
Hispanic or Latino*	11.3% (8)

144 participants were included in melanoma clinical trials within the United States and reported race and ethnicity. The proportion of Black, Asian, Hispanic, and more than one race participants was lower than the racial and ethnic distribution in the U.S. as reported by the U.S. Census Bureau. (Table 2). Conversely, there was a larger proportion of White participants in clinical trials compared to the proportion of White individuals in the U.S. Census. Similarly, there were a smaller proportion of Black, Asian and Hispanic participants in clinical trials compared to the SEER study (Table 2).

Table 2
Title: Comparison of racial and ethnic representation in U.S, clinical trials compared to US Census and SEER populations for ALM
Race and Ethnicity	Participants across US clinical trials (n = 144)	US Census Bureau Population Estimates	SEER Study Participants (n = 1082)
White	88.9% (128)	75.3%	69.8% (755)
Black	4.2% (6)	13.7%	7% (76)
Asian	2.8% (28)	6.4%	8% (87)
Two or more races	0.6% (1)	3.1%	-
Hispanic or Latino*	11.3% (8)	19.5%	15.2% (164)

In this review of clinical trials for ALM, we found that among the five studies reporting race and ethnicity, participants with skin of color were underrepresented relative to both the U.S. Census Bureau and the previously published ALM SEER study [6, 7]. Notably, ethnicity was reported in only three studies, highlighting the need to improve both race and ethnicity reporting in published clinical trials.

An important limitation of this study is that none of the included clinical trials differentiated racial and ethnic composition of participants specifically with ALM, which prevents us from determining the exact demographic of this subgroup. However, ALM represented the second largest proportion of participants, following mucosal melanoma, which is also more prevalent in minority populations [3]. Thus, the findings from this study are still informative regarding the racial and ethnic representation in histologic subtypes that disproportionately affect minority groups.

Additionally, the small sample size and the broad classifications used for race and ethnicity did not have the granularity required to provide insights into subgroup compositions. Given the ancestral differences and resulting genetic variation across racial and ethnic groups, more precise demographic classifications may heighten understanding of differences in trial outcomes across diverse populations. This highlights the urgent need for the systematic inclusion of racial and ethnic minority populations in ALM clinical trials, as well as more detailed demographic reporting for individual tumor types in studies encompassing multiple melanoma subtypes.

Increasing the racial and ethnic diversity, as well as global inclusivity of clinical trials for ALM, is especially pertinent given the differences in prevalence and participant demographics worldwide. Improving public awareness of clinical trials, conducting trials in racially and ethnically diverse areas, and addressing the financial and language barriers that limit participation, may increase diverse representation in future studies. Furthermore, improving global inclusivity, specifically in low- or middle-income countries, will also require increased funding and modulations to current regulatory processes that affect clinical trial approval [1]. Identifying and implementing global and inclusive solutions to these barriers will be essential for improving diversity in future clinical trials for ALM.

Author Contribution

FS and RPL conceptualized the project. FS, DP, and RPL all contributed to manuscript writing and reviewing.

Acknowledgement

Not applicable.

The authors declare that they have no conflict of interest.

Adewole T, Albrecht B, Beg S, Brawley O, Chang IF, Daly B et al (2024) Advancing Global Health Equity in Oncology Clinical Trial Access. Cancer Discov 14(12):2317–2323
Basurto-Lozada P, Molina‐Aguilar C, Castaneda‐Garcia C, Vázquez‐Cruz ME, Garcia‐Salinas OI, Álvarez‐Cano A et al (2021) Acral lentiginous melanoma: Basic facts, biological characteristics and research perspectives of an understudied disease. Pigment Cell Melanoma Res 34(1):59–71
Brunsgaard EK, Wu YP, Grossman D (2023) Melanoma in skin of color: Part I. Epidemiology and clinical presentation. J Am Acad Dermatol 89(3):445–456
Carvalho LAD, Aguiar FC, Smalley KSM, Possik PA (2023) Acral melanoma: new insights into the immune and genomic landscape. Neoplasia 46:100947
Dugan MM, Perez MC, Karapetyan L, Zager JS (2024) Management of acral lentiginous melanoma: current updates and future directions. Front Oncol. ;14
Huang K, Fan J, Misra S (2020) Acral Lentiginous Melanoma: Incidence and Survival in the United States, 2006–2015, an Analysis of the SEER Registry. J Surg Res 251:329–339
U.S. Census Bureau QuickFacts: United States [Internet]. Washington, D.C: U.S. Census Bureau; Available from: https://www.census.gov/quickfacts/fact/table/US

No competing interests reported.

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Reviewers agreed at journal
24 Nov, 2025
Reviewers invited by journal
23 Nov, 2025
Editor assigned by journal
14 Nov, 2025
Submission checks completed at journal
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First submitted to journal
12 Nov, 2025

You are reading this latest preprint version

Racial and ethnic representation across acral lentiginous melanoma clinical trials

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Abstract

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Author Contribution

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