Clinical and Economic Outcomes in Patients with Transfusion-Dependent β-Thalassemia and Patients with Sickle Cell Disease with Recurrent Vaso-Occlusive Crises Receiving Hematopoietic Stem Cell Transplants in the United States

Background: Transfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD) are inherited blood disorders caused by mutations in the β-globin gene, resulting in abnormal, reduced, or absent expression of hemoglobin. TDT is characterized by ineffective red blood cell production that leads to chronic anemia, need for regular red blood cell transfusions (RBCTs), and organ complications. SCD is characterized by sickle-shaped red blood cells that cause vaso-occlusive crises (VOCs), hemolysis, and end-organ damage. Hematopoietic stem cell transplant (HSCT) is currently the only curative option for patients with TDT and patients with SCD. There is limited research on the frequency and outcomes of HSCT in these two patient populations. This study describes the economic and clinical outcomes for a combined population of patients with TDT and patients with SCD with recurrent VOCs who received HSCTs in the United States.

Methods: This retrospective cohort study used administrative claims from the Merative^TM Commercial, Medicare, and Multi-State Medicaid Databases to identify patients with ≥1 inpatient or ≥2 outpatient claims for β-thalassemia or SCD between March 1, 2010, and March 1, 2019. Eligible patients with TDT were required to have ≥8 discrete RBCTs in any 12-month period on or after the date of the earliest qualifying β-thalassemia claim. At least 3 days between service dates of RBCT claims were required to be considered discrete RBCTs. Patients with TDT were required to have 1 year of continuous enrollment after their first transfusion to be included. Eligible patients with SCD with recurrent VOCs were required to have ≥2 diagnosed VOCs per year in any 2 consecutive years after and including the first qualifying SCD claim. A VOC was defined as inpatient or outpatient claim of acute chest syndrome, priapism, SCD crisis, or splenic sequestration; at least 3 days between VOC claims were required to be considered discrete VOCs. Eligible patients with SCD with recurrent VOCs were required to have 24 months of continuous enrollment before the second VOC in the second consecutive year and 12 months of continuous enrollment after. Patients with TDT and patients with SCD who met the above criteria and received an HSCT were included in the analysis set. Patients receiving HSCT were identified utilizing relevant procedure codes. The index date was the date of transplant. Patients were followed from the index date to the earliest of end of enrollment, death, or end of study period (March 1, 2020). Demographics were assessed at the index date, and clinical complications, healthcare resource utilization, and costs were descriptively summarized in the post-index period. Costs were based on paid amounts of adjudicated claims and patient cost-sharing and included costs in the 10 days before the index date to account for pre-transplant healthcare services associated with the transplant.

Results: Two hundred thirty-four and 3500 patients met the criteria for TDT and SCD with recurrent VOCs, respectively, for a total of 3734 patients. Of that total, 62 patients (1.66%) underwent a transplant and were therefore included in the analysis cohort. Mean patient age at the index date was 12.6 years, and 46.8% were female. A proportion of transplant patients experienced graft versus host disease (GvHD) (37/62; 59.7%), unspecified HSCT complications (33/62; 53.2%), or bone marrow transplant rejection or failure (6/62; 9.7%) post-transplant. Average length of stay for the index HSCT admission was 42 days; in the first year post-transplant, patients averaged 58.3 days in the hospital. Total costs in the first 100 days and 1 year post-transplant were $442,752 and $623,301, respectively. Inpatient costs accounted for 93.7% and 88.7% of costs at 100 days and 1 year, respectively.

Conclusions: This retrospective cohort study suggests that only a small proportion of patients with TDT and patients with SCD with recurrent VOCs receive HSCTs. Many patients who undergo transplants experience clinical complications, including graft failure and GvHD, and substantial economic burden. Given the limited utilization and potential safety risks of HSCT, additional curative treatment approaches are needed for patients with TDT and patients with SCD with recurrent VOCs.

Udeze:Vertex Pharmaceuticals Incorporated: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company. Evans:Merative: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company, Research Funding; IBM Watson Health: Current equity holder in private company, Current holder of stock options in a privately-held company, Ended employment in the past 24 months. Yang:Vertex Pharmaceuticals Incorporated: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company. Lillehaugen:Merative: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company, Research Funding; IBM Watson Health: Current equity holder in private company, Current holder of stock options in a privately-held company, Ended employment in the past 24 months. Manjelievskaia:IBM Watson Health: Current equity holder in private company, Current holder of stock options in a privately-held company, Ended employment in the past 24 months; Merative: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company. Mujumdar:Vertex Pharmaceuticals Incorporated: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company; Sanofi Pharmaceuticals Incorporated: Current equity holder in private company, Current holder of stock options in a privately-held company, Ended employment in the past 24 months. Li:Vertex Pharmaceuticals Incorporated: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company. Andemariam:Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Hemanext: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Aruvant: Consultancy, Membership on an entity's Board of Directors or advisory committees; Shenox: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk A/S: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Vertex: Consultancy, Membership on an entity's Board of Directors or advisory committees; Emmaus: Consultancy, Membership on an entity's Board of Directors or advisory committees; CRISPR Therapeutics AG: Consultancy, Membership on an entity's Board of Directors or advisory committees; Terumo BCT: Consultancy, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees.