Real-World Patient Characteristics and Treatment Patterns in Patients with Chronic Graft-Versus-Host Disease Receiving Belumosudil in the United States
Authors: Yu Jingbo , Moore Kristin J. , Engel-Nitz Nicole M. , DuCharme Mary , Thomas Britnie , Galvin John , Bhatt Valkal 
Published: December 2024

Introduction: Chronic graft-versus-host disease (cGVHD) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). cGVHD treatment options after corticosteroid failure have evolved, with multiple FDA-approved modern agents (ruxolitinib [RUX], belumosudil [BEL], ibrutinib). RUX was approved by FDA in 2021 for patients (pts) aged ≥12 years with cGVHD and failure of ≥1 prior lines of systemic therapy, based on findings from the REACH3 study. BEL was approved by the FDA in 2021 for pts aged ≥12 years with cGVHD and failure of ≥2 prior lines of systemic therapy, based on the results of the ROCKstar study. This analysis describes the real-world characteristics and management of pts with cGVHD with BEL. Real-world evidence of treatment patterns with other contemporary cGHVD agents has been reported previously (Van Der Wagen L, et al. Hemasphere. 2022;206(S3):1266-7; Linn SM, et al. Leuk Res. 2023;134:107387; Yu J, et al. Transplant Cell Ther. 2024;30(2_suppl):S286-7). An understanding of the real-world management of cGVHD with BEL will further elucidate treatment patterns in pts with cGVHD and identify areas of unmet need.
Methods: This study included closed claims from commercial, Medicare/Medicare Advantage, and Medicaid health plan members of any age with evidence of allo-HSCT and cGVHD diagnosis during the study period (January 1, 2019-December 31, 2023) from the Komodo Healthcare Map. The earliest cGVHD diagnosis and prescription claims were considered the diagnosis date and index date, respectively; pts with ≥6 months of health insurance coverage (or less due to death) before and after index were included; they were excluded if pregnant or missing demographic data. Follow-up continued until death, plan disenrollment, or end of the study period. Treatment dose and treatment duration were calculated from pharmacy claim refill records. Lines of therapy (LOTs, monotherapy or combination) were evaluated from the diagnosis date to the end of follow-up. cGVHD treatments used concurrently were defined as combination therapy.
Results: A total of 181 pts initiated BEL and were included in the analysis. Mean age was 48 years, with 7.2% and 19.3% of pts aged &lt;18 years and ≥65 years, respectively; 56.9% were male. Most pts (58.6%) had commercial insurance, 23.8% had Medicaid, and 17.7% had Medicare; 51 pts (28.2%) initiated BEL in 2021, 87 (48.1%) in 2022, and 43 (23.8%) from January to May 2023. Pts initiated BEL a median of 489 days after cGVHD diagnosis, mostly in later LOTs (4th LOT, 33.7%; 5th-7th, 33.1%; 3rd, 14.9%; 2nd, 13.8%; 1st, 4.4%). Prior regimens included RUX monotherapy (22.5%), calcineurin inhibitors (CNIs; 16.8%), and CNIs with RUX (14.5%); 65.8% of pts used RUX at any time from diagnosis to index. In the index LOT, BEL was prescribed alone or with corticosteroids for 45.9% of pts and in combination for 54.1% (+ RUX in 22.1% and + extracorporeal photopheresis in 19.9%, with/without other therapies). The median follow-up period was 449 days (IQR, 301-711 d). The median duration of BEL index LOT was 133 days (IQR, 60-276 d). By the end of follow-up, 12.7% of pts continued their initial BEL LOT, 20.4% added therapies, and 27.1% switched therapies; the rest (39.8%) discontinued the LOT, 24% of whom were rechallenged with BEL after a median of 45 days (IQR, 39-78 d). The median BEL starting dose was 200 mg/d (IQR, 200-400 mg/d); 30.4% and 31.6% used a twice-daily (BID) dose of BEL at index and any time, respectively. Among pts with a BEL LOT, 59.1% of pts used a proton pump inhibitor, including 80.0% of pts on BEL BID. Among 160 pts with a BEL refill, 21.9% had a dose change at any time (71.4% and 28.6% with a dose increase or decrease, respectively, at first change); the median time from index to first dose change was 103 days (IQR, 28-199 d).
Conclusions: In real-world practice and this cohort of pts with cGVHD, RUX was a common second-line agent; BEL was mostly used in pts after ≥3 prior LOT. This finding may be confounded by the timing of BEL approval and this analysis. Most pts received BEL in combination; BID dosing was common. On average, pts had changes (ie, discontinuation/interruption, switch, or add-on) in index BEL or BEL combination therapy after 4.5 months. Further data are needed to understand the effect of clinical considerations on treatment patterns and the effects of prior therapies on efficacy and response durability with recently approved therapies for cGVHD.