Belumosudil Commonly Used in Combination and After 3 or More Prior Lines of Therapy in Patients With cGVHD

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According to real-world findings published in Blood, patients with chronic graft-versus-host disease (cGVHD) treated with belumosudil (Rezurock; Kadmon Pharmaceuticals, LLC) primarily received it in combination with other agents and after 3 or more prior lines of therapy. In addition, patients experienced changes in index belumosudil or combination therapy after about 4.5 months.¹

cGVHD is a complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) that may potentially be life-threatening. Currently, the FDA-approved agents for the treatment of patients with cGVHD after corticosteroids have failed include the following: belumosudil, which was approved in July 2021 for patients aged 12 years and older after failure of 2 or more prior lines of systemic therapy, based on findings from the ROCKstar study (NCT03640481)²; and ruxolitinib (Jakafi; Incyte Corporation), which was approved in September 2021 for patients aged 12 years and older after failure of 1 or more prior lines of systemic therapy, based on findings from the REACH3 study (NCT03112603).³ Ruxolitinib and ibrutinib may be used following 1 line of therapy, but belumosudil is indicated after 2 or more lines of therapy. The current study describes real-world characteristics of patients who used belumosudil as treatment for their cGVHD. Additionally, the investigators aimed to further clarify treatment patterns in those with cGVHD to identify areas of unmet need.¹

For this study, the investigators included closed claims from commercial, Medicare or Medicare Advantage, and Medicaid health plan members of any age with evidence of allo-HSCT and cGVHD diagnosis from January 1, 2019, through December 31, 2023, from the Komodo Healthcare Map. The authors defined the earliest cGVHD diagnosis and prescription claims as the diagnosis date and index date, respectively. In addition, patients with 6 or months of health insurance coverage before and after index were included in the study.¹

Follow-up continued until death, plan disenrollment, or the end of the study period. Further, the investigators calculated treatment dose and treatment duration from pharmacy claim refill records. Lines of therapy—which included both monotherapies and combination therapies—were assessed from the date of diagnosis to the end of follow-up, and treatments used concurrently were defined as combination therapy.

According to the findings, a total of 181 patients with a mean age of 48 years had initiated treatment with belumosudil and were included in the final analysis. Most patients were male (56.9%), had commercial insurance (58.6%), and initiated belumosudil during 2022 (48.1%). The investigators found that the median starting dose of belumodsudil was 200 mg per day (IQR, 200-400 mg/day), with approximately 30.4% and 31.6% receiving a twice-daily (BID) dose of belumosudil at index and any time, respectively. Among patients with a belumosudil line of therapy, approximately 59.1% of patients used a proton pump inhibitor, of which 80.0% of patients were on belumosudil BID. A total of 160 patients refilled belumosudil, and about 21.9% had a dose change at any time (increase at first change: 71.4%; decrease at first change: 28.6%). The observed median time from index to first dose change was about 103 days (IQR, 28-199 days).¹

Further, patients initiated belumosudil a median of 489 days following cGVHD diagnosis, and often in later lines of therapy (first: 4.4%; second: 13.8%; third: 14.9%; fourth: 33.7%; and fifth-seventh: 33.1%). The most common prior regimens included ruxolitinib monotherapy (22.5%), calcineurin inhibitors (CNIs; 16.8%), and CNIs plus ruxolitinib (14.5%), and approximately 65.8% of patients received treatment with ruxolitinib at any time from diagnosis to index. In the index line of therapy, belumosudil was prescribed alone or with corticosteroids for approximately 45.9% of patients and in combination for about 54.1% (belumosudil plus ruxolitinib: 22.1%; and belumosudil plus extracorporeal photopheresis: 19.9%, with or without other therapies).¹

The median follow-up period and duration of belumosudil index line of therapy were about 449 (IQR: 301-711 days) and 133 days (IQR: 60-276 days), respectively. By the end of the follow-up period, approximately 12.7% of patients had continued their initial belumosudil line of therapy, 20.4% added therapies, and 27.1% had switched therapies. The remaining 39.8% had discontinued their line of therapy, of which 24% were rechallenged with belumosudil after a median of 45 days (IQR: 39-78 days).¹

Overall, in a real-world practice setting, the enrolled cohort of patients with cGVHD mostly used belumosudil after 3 or more prior lines of therapy. Additionally, most patients received the treatment in combination with therapies, received ruxolitinib as a second-line agent, and received BID dosing. The investigators noted that further data is necessary to better understand the effect of clinical considerations on treatment patterns as well as the effects of prior therapies on efficacy and response durability with recently approved cGVHD therapies.¹

REFERENCES

1. Yu J, Moore KJ, Engel-Nitz NM, et al. Real-world patient characteristics and treatment patterns in patients with chronic graft-versus-host disease receiving belumosudil in the United States. Blood. 2024;144(Supplement 1):3522. doi:10.1182/blood-2024-208047

2. Efficacy and safety of KD025 in subjects with cGVHD after at least 2 prior lines of systemic therapy. ClinicalTrials.gov identifier: NCT03640481. Updated December 21, 2023. Accessed December 11, 2024. https://clinicaltrials.gov/study/NCT03640481

3. A study of ruxolitinib vs best available therapy (BAT) in patients with steroid-refractory chronic graft vs. host disease (GvHD) after bone marrow transplantation (REACH3). ClinicalTrials.gov identifier: NCT03112603. Updated July 18, 2023. Accessed December 11, 2024. https://clinicaltrials.gov/study/NCT03112603