Updated results from REACH2: Ruxolitinib for steroid-refractory acute GvHD

As previously reported on the GvHD Hub, the initial data from the phase III REACH2 trial uncovered the potential benefit of ruxolitinib over best available treatment (BAT) for patients with steroid-refractory acute graft-versus-host disease (SR-aGvHD). As a result, the oral Janus kinases (JAK) 1 and 2 inhibitor has been approved by the U.S. Food and Drug Administration (FDA) for SR-aGvHD in adult and pediatric patients aged ≥ 12 years with SR-aGvHD.

During the 47th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT), GvHD Hub Chair, Mohamad Mohty, Hôpital Saint-Antoine and Sorbonne University, Paris, FR, presented the updated 6-month follow-up safety and efficacy data from the REACH2 trial (Figure 1). The GvHD Hub is happy to provide a revised summary.¹

BAT, best available treatment; BID, twice daily; cGvHD, chronic graft-versus-host disease; CNI, calcineurin inhibitor; DoR, duration of response; EFS, event-free survival; FFS, failure-free survival; NRM, nonrelapse mortality; PROs, patient-reported outcome.
*Adapted from Mohty et al.¹

Updated results

• Data cutoff: January 6, 2020.
• For baseline patient characteristics and results as of July 25, 2019, click here.

Efficacy

• Median duration of response, failure free-survival, and event-free survival were longer in patients who received ruxolitinib vs BAT, whereas the probability of relapse/progression and nonrelapse mortality were comparable between treatment arms (Table 1).
• EQ-5D-5L scoring was used to assess patient-reported outcomes. Improvements in mean EQ-5D-5L scores were observed across both treatment arms at week 24, which were more evident in the ruxolitinib arm.
• Of the patients in the ruxolitinib vs BAT arms
  • 29.2% vs 18.7% had developed cGvHD, but fewer patients in the ruxolitinib arm developed severe cGvHD (4 vs 7).
  • 22.1% vs 14.8% had completely tapered off steroids by day 56.
• Patients who crossed over to ruxolitinib at day 28 demonstrated responses comparable to those observed in the ruxolitinib arm at primary analysis.

Table 1. Outcomes of patients receiving ruxolitinib vs BAT in the REACH2 trial*

BAT, best available treatment; DoR, duration of response; EFS, event-free survival; FFS, failure-free survival; NRM, nonrelapse mortality. *Adapted from Mohty et al.1
Outcome	Ruxolitinib	BAT	HR	95% CI
DoR, days	163	101
FFS, months	4.86	1.02	0.49	0.37–0.63
EFS, months	8.18	4.17	0.80	0.60–1.08
6-month probability, %               Loss of response               Relapse/progression               NRM	8.73 8.5 37.7	37.34 13.5 42.4	—	—
12-month probability, %               Loss of response               Relapse/progression               NRM	10.16 11.1 43.8	37.34 15.1 46.5	—	—

Safety

• No additional safety concerns were observed in the 6-month follow-up.
• In both arms, the primary cause of death was aGvHD:
  • Ruxolitinib arm: 24.3%
  • BAT arm: 25.3%
• Updated safety data from the 6-month follow-up are shown in Table 2.
• The incidence of serious adverse events was lower in the ruxolitinib vs BAT arm when adjusted for treatment exposure:
  • Ruxolitinib arm: 319.4 per 100 patient treatment years
  • BAT arm: 422.7 per 100 patient treatment years
• Cytopenia was the most commonly observed adverse event across both treatment arms.

Table 2. Safety profile of ruxolitinib vs BAT in the REACH2 trial*

AEs, adverse events; BAT, best available treatment. *Adapted from Mohty et al.1
Safety, %	Ruxolitinib (n = 152)	BAT (n = 150)
Grade ≥ 3 AEs	91.4	87.3
Serious AEs	66.4	53.3
AEs leading to discontinuation	27.0	9.3
AEs leading to dose modification	54.6	13.3
Deaths               Fatal serious AEs	53.9 21.7	57.3 21.3

Conclusions

The 6-month follow-up of the REACH2 study highlights the sustained efficacy of ruxolitinib in patients with SR-aGvHD. Ruxolitinib demonstrated superior duration of response, failure-free survival, and event-free survival over BAT. Treatment with ruxolitinib also resulted in noticeable improvement in patient reported outcomes, and a lower probability of disease progression or the need for new systemic therapy for aGvHD. The safety profile of ruxolitinib in this setting was consistent with the primary analysis.

The GvHD Hub was happy to speak to Mohamad Mohty at the EBMT 2021, who addressed the question, What is the risk of losing response to ruxolitinib over time? You can watch the interview below.

Further resources

Ruxolitinib is also being investigated for the treatment of SR-chronic GvHD in the phase III REACH3 trial, and was granted priority review by the FDA for this indication in February 2021.