Characterization of Real-World Chronic Graft-Versus-Host-Disease Patients Receiving Belumosudil

Introduction

Chronic graft-versus-host-disease (cGVHD) is a common complication of hematopoietic stem cell transplant (HSCT). cGVHD is characterized by inflammation and fibrosis that negatively impact multiple organ systems, resulting in substantial morbidity and mortality. While many systemic therapies are available to treat cGVHD, these therapies are associated with adverse events that may limit treatment adherence or lead to discontinuation. In July 2021, the Rho-associated coiled-coil kinase 2 (ROCK2) inhibitor belumosudil was approved by the United States Food and Drug Administration for the treatment of cGVHD for patients 12 years and older after failure of at least two prior lines of systemic therapy based on the efficacy observed in a randomized, open-label, multicenter trial (NCT03640481). Characteristics of patients being treated with belumosudil outside of a clinical trial have not been described previously. The objective of this study is to understand the real-world, non-clinical trial use of belumosudil for patients with cGVHD.

Methods

This retrospective study describes cGVHD patients recorded in the Komodo closed claims dataset between January 2016 and March 2022. The final cohort of interest included patients who were diagnosed with cGVHD (≥1 medical claim with the International Classifications of Disease Version 10 [ICD-10] diagnosis code D89.811), received belumosudil (≥1 claims with National Drug Code 79802020030), and were 12 years of age or older in the year of belumosudil initiation. Patients were required to have at least 36 months of continuous medical and pharmacy enrollment prior to their initial belumosudil prescription to ensure a complete medical diagnosis, treatment, and healthcare utilization history.

Results

A total of 151 patients were identified [median (interquartile range) age of 53 (40-62) years old; 54% female]. Sixty percent (92/151) of the patients had an HSCT within the 36-month observation period, and 73% (67/92) of the patients with an observable HSCT also had a diagnosis for a hematologic cancer in the 3 months prior to their HSCT. The median times from HSCT (in those with a recorded event) and cGVHD diagnoses (in all patients available) to belumosudil initiation were 3.2 (1.7-4.0) and 1.5 (0.5-3.1) years, respectively. During the 36 months pre-belumosudil treatment, common diagnoses included dyspnea (81%, 123/151), cytopenia (79%, 119/151; includes anemia, neutropenia, and thrombocytopenia), and "complications of stem cell transplant" (76%, 115/151; ICD-10 code T86.5). In the 12 months immediately prior to belumosudil initiation, the mean (standard deviation) Charlson Comorbidity Index score was 3.6 (2.2); a median of 9 (4-20) cGVHD-related healthcare encounters occurred; and nearly half of all patients had a hospitalization (all-cause 48%, 73/151; cGVHD-related, 27%, 41/151), with the most frequent primary diagnoses for admission attributed to respiratory illnesses and transplant complications. The majority of patients had received ≥3 lines of cGVHD treatment (85%, 128/151) in the 36 months pre-belumosudil, with a median of 5 (4-6) systemic therapies. Combination therapies containing either calcineurin inhibitors (17%; 25/151) or ruxolitinib (15% 23/151) were the most common lines of therapy immediately prior to belumosudil prescription. Use of strong Cytochrome P450 Family 3 Subfamily A (CYP3A) inducers was not observed during the observation period. In the 12 months prior to belumosudil initiation, 55% (83/151) patients were prescribed proton pump inhibitors. For the first belumosudil prescription that a patient received, 74% (111/151) of patients received once-daily dosing, and 26% (40/151) of patients received twice-daily dosing.

Conclusions

In this real-world data, prior to receiving belumosudil, patients received a median of 5 lines of systemic therapies at a median of 1.5 years from cGVHD diagnosis. Patients displayed multiple comorbidities and frequent hospitalizations that could complicate clinical management with existing cGVHD therapies. There is an unmet need for safe and effective treatment for cGVHD patients. Further research is needed to describe outcomes for patients being treated with belumosudil.

Gergis:Novartis: Honoraria; Kite Pharma: Speakers Bureau; Takeda: Research Funding; Precision: Research Funding. Nicholls:Sanofi: Current Employment, Current equity holder in publicly-traded company. Potukuchi:Sanofi: Current Employment, Current equity holder in publicly-traded company. Kabadi:Sanofi: Current Employment, Current equity holder in publicly-traded company. Verma:Trinity Life Sciences: Current Employment. Patel:Trinity Life Sciences: Current Employment. Li:Trinity Life Sciences: Current Employment. Milgroom:Trinity Life Sciences: Current Employment. Skaar:Trinity Life Sciences: Current Employment, Current holder of stock options in a privately-held company. Ieyoub:Sanofi: Current Employment; Kadmon: Ended employment in the past 24 months.

In the time period examined in this retrospective claims analysis, medications other than belumosudil (e.g., ruxolitinib, calcineurin inhibitors, etc.) may have been used off-label for the treatment of cGVHD.