Sivaraman, Smitha

Abstract Introduction Patients with hematologic malignancies (HM) who are eligible for allogeneic hematopoietic cell transplant (allo-HCT) often lack an HLA-matched related donor (MRD) and rely on unrelated donors for a matched or mismatched unrelated donor (MUD or MMUD) or on umbilical cord blood (UCB). It is well known that racial minorities are underrepresented in donor registries. Objective Omidubicel, an advanced cell therapy for allo-HCT, demonstrated superior hematopoietic recovery and clinical outcomes compared with standard UCB (NCT02730299). We hypothesized the impact of omidubicel access on racial and ethnic health disparities in a projection model. Methods A model was developed to project allo-HCT access and clinical outcomes in a hypothetical population of 10,000 allo-HCT-eligible US patients with HM lacking an HLA-MRD. Outcomes associated with omidubicel, MUD, MMUD, haploidentical or UCB HCT, or no transplant were assessed by race/ethnic group. Model inputs, including clinical outcomes for each HCT type, were drawn from clinical trials, public CIBMTR and US Department of Health and Human Services data, and published studies. Increasing omidubicel use was modeled, with proportional reductions in other allo-HCT types or no transplant. Results In a modeled population of 10,000 patients, 5,956 (60%) received allo-HCT utilizing current donor sources (MUD, MMUD, haploidentical, UCB) with no omidubicel (status quo). While 80% of white patients underwent allo-HCT, only 40% of Hispanic, 32% of Asian, and 22% of Black patients underwent allo-HCT. Mean time from selecting graft to HCT was 11.5 weeks. Including those not transplanted, 1-year OS was 62% overall, ranging from 56% (Black) to 65% (White). Modeled increases in omidubicel use in eligible patients were associated with higher proportions of patients undergoing allo-HCT, decreased time to HCT, and increased 1-year OS. Improvements were greatest among racial minorities. Assuming 20% omidubicel use, the proportion of patients receiving allo-HCT increased by 71% in Black, 43% in Asian, 30% in Hispanic, and 5% in White patients. Modeled time to allo-HCT improved as well. Discussion Access to omidubicel is projected to decrease time to allo-HCT, improve outcomes overall, with greatest improvements among racial and ethnic groups underserved by the status quo, thus helping to reduce racial disparities and improving health equity in allo-HCT.

Abstract Background Previous studies report increasing cholangiocarcinoma (CCA) incidence up to 2015. This contemporary retrospective analysis of CCA incidence and mortality in the US from 2001-2017 assessed whether CCA incidence continued to increase beyond 2015. Patients and Methods Patients (≥18 years) with CCA were identified in the National Cancer Institute Surveillance, Epidemiology, and End Results 18 cancer registry (International Classification of Disease for Oncology [ICD-O]-3 codes: intrahepatic [iCCA], C221; extrahepatic [eCCA], C240, C241, C249). Cancer of unknown primary (CUP) cases were identified (ICD-O-3: C809; 8140/2, 8140/3, 8141/3, 8143/3, 8147/3) because of potential misclassification as iCCA. Results Forty-thousand-and-thirty CCA cases (iCCA, n=13,174; eCCA, n=26,821; iCCA and eCCA, n=35) and 32,980 CUP cases were analyzed. From 2001-2017, CCA, iCCA, and eCCA incidence (per 100 000 person-years) increased 43.8% (3.08 to 4.43), 148.8% (0.80 to 1.99), and 7.5% (2.28 to 2.45), respectively. In contrast, CUP incidence decreased 54.4% (4.65 to 2.12). CCA incidence increased with age, with greatest increase among younger patients (18-44 years, 81.0%). Median overall survival from diagnosis was 8, 6, 9, and 2 months for CCA, iCCA, eCCA, and CUP. From 2001-2016, annual mortality rate declined for iCCA (57.1% to 41.2%) and generally remained stable for eCCA (40.9% to 37.0%) and for CUP (64.3% to 68.6%). Conclusions CCA incidence continued to increase from 2001-2017, with greater increase in iCCA versus eCCA, whereas CUP incidence decreased. The divergent CUP versus iCCA incidence trends, with overall greater absolute change in iCCA incidence, provide evidence for a true increase in iCCA incidence that may not be wholly attributable to CUP reclassification.