Addressing Patient Representation in Hematopoietic Cell Transplant Clinical Trials: Insights Gained through the Access Trial

Background: More patients with diverse ancestry and lower socioeconomic status (SES) are diagnosed annually with hematopoietic cell transplant (HCT)-eligible diseases than receive HCT, reflecting access barriers resulting in underrepresentation in clinical trials. The NMDP-sponsored, CIBMTR-led ACCESS (NCT04904588) trial studied safety and efficacy of peripheral blood stem cell allografts from mismatched unrelated donors (MMUD) in adults with hematologic malignancies receiving myeloablative (MAC) or reduced intensity/non-myeloablative conditioning (RIC/NMA) combined with post-transplant cyclophosphamide, mycophenolate mofetil, and tacrolimus as graft-versus-host disease prophylaxis. Analysis from the initial RIC/NMA stratum showed that 51% (n=36) of patients were ethnically diverse (ED) and had a 1-year overall survival of 79% (Al Malki et al. ASCO 2024). ED patients were younger and had higher financial toxicity and social vulnerability index (SVI) than non-Hispanic White (NHW) patients (Yusuf et al. 2024 Tandem Meetings). Enrollment of adult patients on both strata was completed in February 2024. Herein we provide key baseline characteristics to further define profiles that might influence social needs and trial participation of ED patients.

Methods: To enroll on ACCESS, patients required an unrelated donor (URD) matched at 4-7/8 HLA alleles (HLA-A, B, C, and DRB1) and aged 18-35 years. Recipients without an available 8/8 related or URD and lacking HLA-specific antibody (anti-HLA-Ab) to any mismatched allele/antigen were eligible. Donor ancestry and recipient utilization of NMDP patient support were collected through NMDP operations. Social drivers/determinants of health (SDOH), including COmprehensive Score for financial Toxicity (COST) and SVI, and patient reported outcomes (PRO) were collected on enrolled patients and compared between NHW and ED subjects, defined as patients having any race and ethnicity besides NHW (AFA, non-Hispanic Black/African American; API, Asian Pacific Islander; HIS, Hispanic; NAM, Native American; MLT, multiple; and UNK, unknown). Wilcoxon rank sum and Fisher exact tests were used for continuous and categorical variables, respectively, to measure statistically significant differences between groups (p<0.05).

Results: Of 268 adult patients, 51% were males, 69% had acute leukemia, and 51% were ED: 28% (n=75) HIS, 13% (n=34) AFA, 8% (n=22) API, 1% (n=3) NAM, <1% (n=2) MLT, and <1% (n=1) UNK. Most patients received RIC HCT (n=193, 72%) using a 7/8 MMUD (n=183, 68%). No differences in HCT comorbidity indices were noted between NHW and ED patients (p=0.42).

Median donor age was 25 years (18-35 years) and more AFA patients received HCT using a donor above the median age. Of 153 patients with anti-HLA Ab, 58% were female with higher incidence of anti-HLA-Ab noted in patients utilizing MMUD with higher degree of HLA mismatch: 7/8 (n=96) 58%; 6/8 (n=45) 67%; 5/8 (n=9) 75%; and 4/8 (n=3) 100%.

Compared to NHW patients, ED patients were younger (median age: 56 v. 64 years), had higher overall SVI (high SVI: 27 v. 10%), and lived closer to a transplant center (mean distance: 35 vs. 62 miles)(all p<0.01). Baseline PRO data were available in 211 patients (113 NHW, 97 ED, 1 Unknown). More ED patients than NHW reported lower educational attainment (college degree: 21 v. 36%), lower personal income (<$50,000: 51 v. 28%), and higher financial toxicity (mean COST: 21 vs. 28)(all p<0.05). In contrast to NHW patients, a larger proportion of ED patients acknowledged needing a caregiver (39 v. 22%)(p<0.05).

Of 162 (60%) enrolled patients receiving NMDP support services, 121 (44%) received navigation and 84 (31%) received financial assistance. Of these, 90 (56%) were ED and 72 (44%) were NHW. ACCESS trial participants who received navigation or financial assistance lived in an area (ZIP-based) with a lower percentage of the population with a bachelor or graduate degree (33 v. 39%) and median income ($82,000 v. $93,000) than participants who did not receive support (both p<0.05).

Conclusions: Half of adult patients enrolled on the ACCESS trial were ED and had higher social vulnerability needs and obtained more support services compared to NHW patients. The ACCESS trial expanded access for underserved patients and highlights the need for additional support strategies to ensure representation of ED patients in HCT clinical trials.