Disparities in acute lymphoblastic leukemia risk and survival across the lifespan in the United States of America

Abstract

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer but is less frequent in adolescents and young adults (AYAs) and is rare among older adults. The 5-year survival of ALL is above 90% in children, but drops significantly in AYAs, and over half of ALL-related deaths occur in older adults. In addition to diagnosis age, the race/ethnicity of patients consistently shows association with ALL incidence and outcomes. Here, we review the racial/ethnic disparities in ALL incidence and outcomes, discuss how these vary across the age spectrum, and examine the potential causes of these disparities. In the United States, the incidence of ALL is highest in Hispanics/Latinos and lowest in Black individuals across all age groups. ALL incidence is rising fastest in Hispanics/Latinos, especially in AYAs. In addition, survival is worse in Hispanic/Latino or Black ALL patients compared to those who are non-Hispanic White. Different molecular subtypes of ALL show heterogeneities in incidence rates and survival outcomes across age groups and race/ethnicity. Several ALL risk variants are associated with genetic ancestry, and demonstrate different risk allele frequencies and/or effect sizes across populations. Moreover, non-genetic factors including socioeconomic status, access to care, and environmental exposures all likely influence the disparities in ALL risk and survival. Further studies are needed to investigate the potential joint effects and interactions of genetic and environmental risk factors. Improving survival in Hispanic/Latino and Black patients with ALL requires advances in precision medicine approaches, improved access

Increased Risk of Acute Lymphoblastic Leukemia in Adult Patients with GSTM1 Null Genetic Polymorphism

“…In this study, the most prevalent type of ALL was B –ALL (80.5% of the cases) which is similar to the reported rates. 3 In the current study, although the frequency of GSTT1 null polymorphism was higher in patients as compared with controls (22.7% Vs 14.8%); this difference was statistically insignificant (p>0.05). Furthermore, no association between GSTT1 polymorphism and ALL susceptibility was found.…”

“… 1 , 2 Ethnicity has also shown positive association with the incidence and outcome of ALL. 3 Although, the exact etiology of ALL is not well defined, certain genetic disorders (Down syndrome, Fanconi’s anemia, Bloom syndrome, ataxia telangiectasia and Nijmegen breakdown syndrome), ionizing radiation, chemicals (pesticides, benzene), and viral infections (Epstein-Barr Virus and Human Immunodeficiency virus) have been proved to be the predisposing factors for the development of ALL. Additionally, somatic chromosomal aberrations including t (12;21) [ETV6-RUNX1], t(1;19) [TCF3-PBX1], t(9;22) [BCR-ABL1] are the hallmark of ALL.…”

Brexucabtagene Autoleucel (Tecartus)

“…One clinical study (the ZUMA-3 study) is included the CADTH systematic review� The ZUMA-3 study 9 (N = 71) is an ongoing phase I/II, open-label, single-arm study that evaluated the efficacy and safety of brexu-cel in patients with R/R B-cell ALL. The primary end point was overall complete remission (OCR) rate (defined as CR plus CR response with incomplete hematologic recovery [CRi]) by central assessment� Secondary end points included OS, relapse-free survival (RFS), duration of remission (DOR), MRD-negative rate, subsequent allo-SCT rate, and HRQoL� A total of 55 of the 71 patients enrolled received brexu-cel and were included in the primary efficacy and safety analyses.…”

“…The sponsor incorporated a cure point at the 2-year time point of the model� Patients who were event-free at the cure time point were deemed functionally cured and incurred an age-adjusted and sex-adjusted background mortality, sourced from Statistics Canada life tables� 8 However, that background mortality was further increased by fourfold based on literature, to represent the patient population cured of B-cell precursor ALL� 9 The duration of treatment for the comparators was obtained from the literature� The sponsor assumed an average of 2�24 cycles of therapy for blinatumomab, a maximum of 5 28-day cycles and 1 21-day cycle for inotuzumab, a maximum of 4 cycles for salvage chemotherapy, and 90 days for TKIs� In the base-case analysis, the sponsor used the maximum treatment cycles for inotuzumab, and salvage chemotherapy�…”

“…Disparities in Incidence, Treatment, and Outcomes of ALL Literature has suggested that there are disparities in incidence of ALL where it has been identified as more prevalent among Hispanic/Latinx populations in the US� 9 Disparities in access to treatment and specialized care for ALL have also been identified for Hispanic and non-Hispanic Black populations in the US. 10 These studies have described how disparities in access to care and treatment are further exacerbated for those living in socioeconomically deprived areas that are less likely to host specialized treatment centres� 10 Patients with limited resources or social support may also face challenges in accessing treatment given the costs of travel, childcare, and missing work� 10 These studies point toward the importance of attending to social determinants of health by addressing socioeconomic and institutional barriers of access for disadvantaged populations in the context of those living in Canada� Clinical experts and published literature also indicated that there are disparities in outcomes across demographics related to age and race� [9][10][11] Significant disparities have been noted regarding 5-year survival outcomes between pediatric, adolescent and young adult (AYA), and adult populations. 9 According to US-based data, while 5-year survival for children has been noted to be upward of 90%, for AYAs this figure drops to 60% to 85%, and it falls even further, to 30%, for adults, who make up about 54% of ALL deaths� 9,11 In Canada, clinical experts suggested that much older patients (those aged 70 years of older) may expect even poorer outcomes because they are generally considered ineligible for a common second-line treatment, allo-SCT�…”