The Burden of Illness and the Incremental Burden of Transfusion Dependence in Myelofibrosis in the United States

Introduction: Myelofibrosis (MF) is a rare myeloid neoplasia characterized by inflammation, fibrosis, and degradation of the bone marrow niche. Anemia is a key hallmark of MF which increases in frequency and severity with disease progression. Janus Kinase inhibitors are the standard of care for MF but can exacerbate anemia. About one-quarter of patients are transfusion-dependent at time of diagnosis and nearly all will develop transfusion dependence, which is associated with a poor prognosis¹ However, the burden of illness of MF-associated anemia and transfusion dependence remains poorly defined. This study examined the burden of illness among these patients, including costs and healthcare resource utilization (HCRU).

Methods: This retrospective study examined patients with ≥2 claims with International Classification of Diseases, 10th revision (ICD-10) diagnosis codes for MF (D75.81, D47.4) in the IBM MarketScan claims dataset (2016-2021). The most recent two calendar years with continuous enrollment were examined for each patient. A one-year lookback provided baseline data, including prior treatment and comorbidities. Outcomes were assessed in the calendar year beginning January 1 of the second year of the study period (i.e., the index date). Anemia was defined by diagnosis codes or anemia-related treatments. Transfusion dependency was defined as ≥2 transfusions in any one month. Transfusion requiring patients below this threshold were considered transfusion independent. Transfusion dependent and independent patients were exact-matched based on age, sex, and Charlson Comorbidity Index (CCI) score. Outcomes included adverse events (AEs; based on ICD-10 codes), HCRU, and costs. Statistical significance was assessed by t-tests or chi-squared tests for continuous and proportional metrics.

Results: Prior to matching, 1535 transfusion independent (of which 295 required occasional transfusions) and 139 transfusion dependent patients with MF were identified. Within the total MF population, 64% (1072/1674) of patients were anemic. The mean transfusion episode cost was US$3,790. After matching, the transfusion independent and transfusion dependent cohorts included 133 patients (47% female, mean age 66, and mean CCI 3.0). Among transfusion independent patients, 30% required occasional transfusions but were not transfusion dependent. In the observation year, transfusion dependent patients showed statistically significant increases (p<0.05) in risk for 16 AEs (Figure 1), including neutropenia (OR 12.3), thrombocytopenia (OR 10.7), fever (OR 7.8), and peripheral edema (OR 6.1). Transfusion dependent patients also showed statistically significant increases in HCRU, including mean hospitalizations (2.0 vs. 0.3), rate of hospitalization (75% vs. 22%), mean emergency department visits (2.2 vs. 0.7), and mean outpatient visits (48.9 vs. 9.0) (all p<0.05). Non-transfusion associated visits to oncologists (6.0 vs. 0.4) and hematologists (2.3 vs. 0.8) were significantly increased in the transfusion dependent population (p<0.05). Transfusion dependent patients had nearly a ten-fold higher mean annual total medical cost of $255,190 versus only $27,789 for transfusion independent patients (Figure 2, p<0.0001). The mean pharmacy cost of $60,854 in transfusion dependent patients was also significantly greater than the $40,038 mean pharmacy cost in transfusion independent patients (p=0.0118). Patient out-of-pocket costs were also 70% more in transfusion dependent patients ($2,463 vs. $1,450, p=0.0003).

Conclusions: Patients with MF and transfusion dependence demonstrated substantial and statistically significant increases in many AEs (including hematological non-anemic AEs and non-hematological AEs), HCRU (including HCRU not associated with transfusions), and cost over a one-year period compared to matched patients with MF who were transfusion independent. Overall, these results suggest a high clinical and economic burden for transfusion dependent MF patients that requires further study. This study highlights the need for additional therapeutic options to limit progression to transfusion dependence or offset costs for patients with MF.

Gerds:Imago BioSciences: Research Funding; Kratos Pharmaceuticals: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb/Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Research Funding; Accurate Pharmaceuticals: Research Funding; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sierra Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Morphosys/Constellation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees. Harrison:Incyte: Speakers Bureau; AOP Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Keros: Consultancy; EHA: Other: Leadership role; MPN voice: Other: Leadership role; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Geron: Membership on an entity's Board of Directors or advisory committees; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees; Galecto: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sierra: Honoraria; AbbVie: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Promedior: Membership on an entity's Board of Directors or advisory committees; Galacteo: Membership on an entity's Board of Directors or advisory committees; Constellation Pharmaceuticals, Inc., a MorphoSys Company: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings, Research Funding. Thompson:Sierra Oncology: Current Employment. Snopek:Sierra Oncology: Current Employment. Pemmaraju:stemline: Consultancy; abbvie: Consultancy; immunogen: Consultancy; mustangbio: Research Funding; incyte: Consultancy; novartis: Research Funding; pacylex: Consultancy, Research Funding; samus: Research Funding; daiichi sankyo: Research Funding; cellectis: Research Funding; cellularity: Research Funding.