Real-world effectiveness of belumosudil for chronic GVHD by line of treatment: Analysis of academic and community practice patterns Free

Introduction:

Belumosudil (BEL) is a ROCK2 inhibitor approved by the US FDA for the treatment of steroid-refractory chronic graft-versus-host disease (cGVHD) after ≥2 prior lines of therapy (LOT) in patients 12 years or older. While clinical trials such as ROCKstar demonstrated high response rates and steroid-sparing effects, real-world treatment patterns, sequencing, and optimal timing of BEL initiation in the treatment sequence remain unclear. This study investigates real-world BEL use patterns by LOT across different practice settings.

Methods: The study was conducted using two complementary databases: ROCKreal (academic transplant centers) and MarketScan (mixed academic/community settings) in patients receiving BEL LOTs 3-6. Patient eligibility criteria included age ≥12 years, documented cGVHD diagnosis, and BEL initiation in LOTs 3-6 between March 1, 2015 - March 27, 2024. The MarketScan analysis required continuous enrollment for ≥6 months prior to first BEL initiation, with exclusion of patients with prior cancer relapse. Primary objectives included characterizing treatment patterns and sequencing prior to BEL initiation across both databases. Secondary objectives included describing patient characteristics and comparing overall response rates (ORR) at 6-months for BEL use in ROCKreal database across subsequent LOTs and assessing reasons for switching to BEL.

Results: The current analysis included 113 patients from ROCKreal. The most common treatment prior to BEL was ruxolitinib (RUX) alone or in combination with calcineurin inhibitors (CNIs) or glucocorticoids (GCs), which was consistent across all LOTs. In Marketscan, there were 87 patients initiating BEL and a similar proportion had prior exposure to RUX. In the ROCKreal database, concurrent RUX and BEL was used in 21% and 33% in LOT 3 and LOTs 4-6, respectively. In MarketScan, concurrent use of RUX and BEL was observed in 39% and 43% of patients in BEL LOT 3 and LOTs 4-6, respectively, though the duration of concurrent therapy remains unknown. Primary reasons for switching to BEL in ROCKreal were lack of efficacy (39.6%), physician decision (27.3%), or adverse events (18.0%).

In ROCKreal, patients in BEL LOTs 4-6 had similar organ involvement at BEL initiation (median [inter quartile range, IQR]): 3.0 [2.0, 4.0] compared to BEL LOT 3: 3.0 [2.0, 3.5], though the upper quartile was slightly higher in later lines. The most commonly involved organs were skin (69% in BEL LOT 3, 80% in LOTs 4-6), eyes (65% in LOT 3, 64% in LOTs 4-6), and muscles/joints/fascia (35% in LOT 3, 64% in LOTs 4-6). Pulmonary involvement was present in 33% of LOT 3 and 30% of LOTs 4-6 patients. Comorbidities were common, with pulmonary (56% in LOT 3, 43% in LOTs 4-6) and cardiovascular (41% in LOT 3, 3% in LOTs 4-6) conditions being prevalent.

In the ROCKreal data, patients initiating BEL in LOT 3 or LOTs 4-6 both had responses exceeding the clinically meaningful threshold of 30%; (ORR at 6 months 42.9% vs. 35.7%). Additional analyses of the MarketScan data are ongoing.

Conclusions:

These real-world data demonstrate consistent use of BEL across practice settings, including frequent use of BEL subsequent to treatment with RUX and GCs. The extent of concurrent use of BEL and RUX remains to be further elucidated before the frequency of this approach in real-world management of advanced cGVHD can be fully characterized. In spite of common use of RUX in pre-BEL LOT, ROCKreal data confirm clinically significant 6 month response rates in patients receiving BEL in LOT 3 and LOTs 4-6. There may be a trend toward better responses earlier in the treatment sequence, but this analysis did not adjust for potentially confounding factors. The data from this study to date do not permit discrimination of differences in response rates in patients treated with BEL alone or in combination with other agents, but this merits further exploration.