Abstract D075: Investigating the immuno-biology underlying differential response to immunotherapy in White and non-White patients with metastatic acral melanoma
Authors: Ludford Kaysia , Saberian Chantal , Nabhan Sara K , Gruschkus Stephen , Bernatchez Chantale , Jackson Natalie , Haymaker Cara L , Hwu Patrick , Diab Adi 
Published: September 2020

Abstract
Background: Acral melanoma (ACML), the rarest form of melanoma (MEL) represents 4-6% of all MEL cases however it is the most common subtype darker pigmented individuals accounting for up to 70% of all cases. Checkpoint inhibitors (CPI) have emerged as an efficacious treatment option. In cutaneous melanoma (CtMEL), tumor mutational burden (TMB) correlates with response rate. Despite low TMB in AMEL, responses to CPI parallel those in CtMEL. Given the differences in ethnicity among ACML patients compared CtMEL patients we aimed to study: (i) the correlation between response and TMB, (ii) the relationship between ethnicity and response and (iii) the underlying immune-biology accounting for differential responses. Method: All advanced and metastatic ACML patients (pts) treated with anti-CTLA4 (ipilimumab) or anti-PD1 (pembrolizumab or nivolumab) immunotherapy between March 2011 and January 2019 at MD Anderson Cancer Center, Texas, were included in this retrospective analysis. Clinical response, progression free survival and overall survival (PFS and OS) and their correlation to ethnicity and TMB were evaluated. Objective response was measured using RECIST 1.1 and analyzed using logistic regression. PFS and OS were assessed using the Kaplan Meir method and log-rank test. TMB was predicted using validated algorithm based on a defined gene mutation set obtained using next generation sequencing. Results: 44 pts with Stages III-IV ACML (IIIA: 2%, IIIB 9%, IIIC 27%, IV-M1A: 16%, IV-M1B: 25%, IV-M1C: 20%, IV-M1D2%) were included in the analysis. Median age was 63 years old (39-88) and 60% were men. Of 44 patients 12 (27%) self-identified as Hispanic, 2 as (5%) Asian and 30 (68%) as White. The overall response rate was nearly 5 times times higher in Hispanic compared to White pts (OR 4.60, p-value 0.04). The median TMB in Hispanic patients was 16 mutations/mb compared to 7 mutations/mb in White pts. The median PFS and OS for White pts were 7.2 months and 34.3 months respectively while for Hispanic pts the median PFS and OS were 6.7 (log-rank p=0.69) and 26.1 months (log-rank p=0.38) respectively. In addition to this data deep immune analysis of tumor tissue including nanostring, gene expression and TCR sequencing will be assessed and reported. Conclusions: The data from this small retrospective study suggests that White pts with ACML had low response rates to CPI presumably due to low TMB while interestingly, Hispanic pts, despite relatively low TMB have high response rates paralleling those seen in the overall CtMEL population. Despite higher response rates in Hispanic patients, there was no significant difference in OS. This data together with further immune analysis provides the rationale to design prospective studies to investigate how tumor micro-environment varies with ethnicity. Additionally we will investigate the social and biological determinants that limit survival in Hispanic pts despite higher response rates.
Citation Format: Kaysia Ludford, Chantal Saberian, Sara K Nabhan, Stephen Gruschkus, Chantale Bernatchez, Natalie Jackson, Cara L Haymaker, Patrick Hwu, Adi Diab. Investigating the immuno-biology underlying differential response to immunotherapy in White and non-White patients with metastatic acral melanoma [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D075.