Novel treatments are needed to replace transplant and prevent graft-vs-host disease in order to improve patient outcomes.
An analysis presented during the 2023 Transplantation & Cellular Therapy Meetings highlighted the need for novel treatments to replace transplant, prevent graft-vs-host disease (GVHD), improve patient outcomes, and control healthcare costs as a result of the economic burden from the per-patient cost of allogeneic hematopoietic cell transplant (alloHCT).
Results showed that the current average per-patient medical cost of alloHCT over a lifetime was estimated at $1,247,917, 53% of which was due to treatment for chronic GVHD (cGVHD); the discounted expected quality-adjusted life years (QALY) was 4.7. Based on the expected availability of new cGVHD agents, the future per-patient medical cost of alloHCT was estimated to be between $1,370,839 and $1,616,684 with 4.8 discounted expected QALYs.
In a projection analysis that evaluated the current and future estimated lifetime costs over a 10-year period, data showed that the annual number of alloHCTs was 8326, and 76% of those transplants were for patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndromes (MDS). The average allo-HCT growth, based on the past 5 years, was calculated at 0.34%, along with an average Medicare inflation rate of 2.53%.
“The aggregate costs associated with allo-HCT are expected to increase and pose an increased burden on the healthcare system,” lead study author Miguel-Angel Perales, MD, chief of the Adult Bone Marrow Service at Memorial Sloan Kettering Cancer Center, New York, New York, and coinvestigators, wrote in the poster presented at the meeting. “Novel drugs have recently emerged. Clinical use and data on their utilization and impact are currently sparse.”
The number of HCT procedures has increased annually, the investigators noted. Emerging agents have been designed to address and manage posttransplant complications, such as GVHD. However, such agents are not widely utilized and their impact on clinical practice is unclear.
In the analysis presented, investigators sought to estimate the total lifetime medical costs of an alloHCT patient, and the aggregate lifetime burden over the next decade for incident alloHCT patients while considering newly available therapies for chronic GVHD.
Investigators utilized a 100-day and long-term Semi-Markov Partitioned survival model with peer-reviewed evidence and data from the CIBMTR of US patients with AML, ALL, and MDS who had undergone alloHCT. The clinical inputs studied were overall survival (OS), GVHD-free relapse-free survival (GRFS), incidence of both acute GVHD (aGVHD) and cGVHD, relapse of primary disease, and infections. Economic inputs included alloHCT cost, aGVHD, cGVHD, relapse episode, infection hospitalization, maintenance treatment, and end-of-life costs.
The primary outcomes were total direct medical costs, total expected life years (LYs), and quality-adjusted QALYs. Investigators noted that all cost and outcomes were discounted at 3% annually.
Moreover, patient characteristics, estimated time spent in each health state, OS, and GRFS outcomes came from CIBMTR and published literature data.
Based on the data pulled, the age at transplant was 53 years and 58% were male. Fifty-one percent of patients had AML, 21% had ALL, and 28% had MDS. In related donors (32%), 8% were from bone marrow and 92% were from peripheral blood stem cell (PBSC); in unrelated donors, 9% and 91% were from bone marrow and PBSC, respectively.
Regarding costs, an alloHCT was $182,642, and the 100-day and annual costs of acute GVHD treatment were $79,197 and $158,938, respectively. For cGVHD treatment, the current cost was $220,202, with an estimated 25% future uptake in costs totaling $261,413 and an estimated 75% future uptake totaling $343,836. Relapse episodes had a cost of $206,003 and infection hospitalization at $53,214; the annual costs of maintenance sorafenib (Nexavar) and imatinib mesylate (Gleevec) were $277,765 and $184,861, respectively. End-of-life costs were $174,102.
Patient utilities were also calculated, posttransplant without GVHD (0.86) and with GVHD (current, 0.69; future, 0.76), and relapsed/progressed AML (0.53), ALL (0.74), and MDS (0.60); a disutility was infection (-0.23).
The projection analysis was run to account for a likely increased growth of allogeneic transplants in the projected years 1 through 10. Here, an average annual growth rate was applied to the current number of alloHCT recipients; this was based on the mean alloHCT growth from the past 5 years. Based on this information, there is an estimated 6544 allogeneic recipients occurring in year 10 and a total of 64,461 alloHCTs over the 10-year span.
Volume and costs were also analyzed in the projection analysis. The cumulative total over the 10-year span was calculated at $92.6 billion. When including the future alloSCT costs with a 25% uptake, this total was $101.7 billion, which was a $9.1-billion net difference vs the current cost; this was $120.0 billion with a 75% uptake, which was a $27.4-billion net difference vs the current cumulative total.
“The analysis suggests that the small gain in QALYs [0.1 QALY average per patient] as a result of new treatment approaches for active [chronic] GVHD would cost an additional $9 billion to $27 billion in the aggregate over 10 years,” the authors noted.
Because 15-year OS and GRFS outcomes were used to inform the model consisted of a cohort of allo-HCT recipients from 2000 to 2005, the authors stated that the data may not fully be representative to outcomes observed in present day—especially as cancer treatment and care continues to evolve and improve.
They added that the OS/GRFS outcomes were adjusted by utilizing data from 2016 to 2019 for the first 3 years, before using the observed trend from a 2000 to 2005 cohort. This permitted the inputs to be more representative of current treatment outcomes.
Further limitations the authors cited were that inputs were obtained from published claims analyses and mirror averages of multiple populations, “which can introduce heterogeneity into the model.” Finally, off-label maintenance therapy for patients with FLT3-ITD–positive AML and Philadelphia chromosome–positive ALL is not fully adopted in clinical practice, so not all patients in these subgroups may receive this treatment. “Incorporating the costs of such treatment may result in an overestimation of the total lifetime costs of allo-HCT,” the authors concluded.
15-year OS and GRFS outcomes used to inform the model consisted of a cohort of allo-HCT recipients from 200