Subgroup analysis of ruxolitinib in patients with steroid-refractory acute GvHD – update from EHA 2020

The main results of the phase III REACH2 trial (NCT02913261), comparing the efficacy and safety of ruxolitinib (RUX) with nine best available therapies (BAT) in patients with steroid-refractory acute graft-versus-host-disease (SR-aGvHD), were published in The New England Journal of Medicine. The study, which was recently summarized on the GvHD Hub, demonstrated significantly improved outcomes in patients treated with RUX compared with BAT.

During the European Hematology Association (EHA) virtual meeting, Robert Zeiser from the University Hospital Freiburg, DE, presented a follow-up analysis of the REACH2 study, which examined responses in different subgroups of patients of the trial. The previously published Day-28 response rate for the overall population was 62.3% with RUX vs 39.4% with BAT (odds ratio [OR] 2.64; p < 0.001). The subsequent analysis of response by baseline characteristics revealed superior efficacy of RUX vs BAT in several subgroups of patients, including those aged 18–65 years. RUX showed better responses irrespective of the severity of aGvHD, organ involvement, donor type, and type of prior conditioning regiment, and prior GvHD therapy used (Table 1).

Table 1. Subgroups with higher overall response rates at Day-28 for RUX vs BAT

aGvHD, acute graft-versus-host disease; CNI, calcineurin inhibitors; GI, gastrointestinal; SR, steroid-refractory
Subgroup	ORR, %
	RUX	BAT
Age group
16-65 years	64.8	38.1
Gender
Female	62.9	39.1
Male	62.0	39.6
Conditioning regimen
Myeloablative	55.3	36.9
Non-myeloablative	71.0	41.5
Reduced-intensity	71.1	40.8
Donor source/ HLA match status
Not related and match	61.5	40.3
Not related and mismatch	71.1	44.4
Related and match	59.3	24.1
aGvHD grade at randomization
Grade II	75.5	50.9
Grade III	56.3	37.5
Grade IV	53.3	23.3
Organ involvement
Liver	44.4	19.2
Lower GI	57.34	33.0
Skin	72.0	47.3
Upper GI	67.9	37.8
Donor type
Not related	64.8	41.0
Related	57.1	36.4
Criteria for SR-aGvHD
Failure on steroid taper	66.0	46.9
Failure to achieve a response after 7 days	56.9	38.1
Progression after ≥ 3 days	66.6	32.6
Prior aGvHD therapy
Steroid + CNI	62.3	40.8
Steroid + CNI + other systemic aGvHD treatment	66.1	38.8

Furthermore, RUX induced higher rates of response at Day 28, which were maintained at Day 56, than BAT (39.6% vs 21.9%; p < 0.001). The cumulative incidence of loss of response at 6 months for RUX and BAT were 9.65% (95% CI, 4.39–17.4) and 39.96 (95% CI, 25.54–52.19), respectively. The safety profile was consistent with that previously reported. There were no new or unexpected safety concerns.