CONFERENCE UPDATE: ASH 2023

Ruxolitinib exhibits sustained efficacy compared to best available treatment in patients with chronic GvHD: 3-year final analysis of the REACH3 study

HEMATOLOGY
08 Feb 2024

STUDY DESIGN

Graft-versus-host disease (GvHD) is a life-threatening complication of allogeneic stem cell transplant (allo-SCT) that occurs in half of the patients who undergo the procedure.1 Although corticosteroids are the first-line treatment options for GvHD, a majority of patients become refractory towards them.1 Ruxolitinib is a Janus kinase (JK)1/JK2 inhibitor that demonstrated notable efficacy over best available treatment (BAT) in the initial analysis of the REACH3 study, exhibiting significantly higher overall response rate (ORR) at 24 weeks of treatment (49.7% vs. 25.6%; p<0.0001).1

The REACH3 study was a randomized phase 3 trial that assessed the efficacy and safety of ruxolitinib and BAT in patients with GvHD.1 329 patients who were aged ≥12 years and developed moderate or severe steroid-refractory/dependent chronic GvHD (cGvHD) after undergoing allo-SCT were randomized 1:1 to receive either ruxolitinib 10mg twice daily (n=165) or BAT (n=164).1 The primary analysis was conducted at week 24, after which BAT patients were allowed to crossover to ruxolitinib, continue BAT, or discontinue and enter long-term follow-up (LTFU).1 Patients randomized to the ruxolitinib group were also allowed to discontinue and enter LTFU or continue treatment.1 The final analysis was conducted at week 156.1

The efficacy endpoints for this final analysis included failure-free survival (FFS), duration of response (DOR), overall survival (OS), and safety outcomes of both treatment groups at week 156.1 ORR and best overall response (BOR) of BAT patients who crossed over to ruxolitinib after week 24 were also analyzed.1

 

Efficacy: 
  • The efficacy endpoints assessed in this final analysis included FFS, DOR, OS of both treatment groups at week 156, as well as ORR and BOR of BAT patients who crossed over to ruxolitinib after week 241
  • The median FFS of the ruxolitinib group was substantially longer compared to the BAT group (38.4 months vs. 5.7 months; HR= 0.361; 95% CI: 0.268-0.485)1
  • Compared to the BAT group, the ruxolitinib group exhibited higher FFS probability at 12 months (64.0% vs. 28.8%), which was also sustained at 36 months (56.5% vs. 18.2%)1
  • At the end of the study, the median DOR was not reached for the ruxolitinib group and was 6.4 months for BAT group1
  • The ruxolitinib group had a higher DOR probability at 12 months (70.2% vs. 39.8%), which was also retained at 36 months (59.6% vs. 26.7%)1
  • The median OS was not reached in either group and no statistical difference in risk of death was observed between the treatment groups1
  • Patients who switched to ruxolitinib after inadequate response to BAT after week 24 (n=70) achieved an ORR of 50.0% and BOR of 81.4%1
  • At 24 weeks, response rates of patients who crossed over to BAT were consistent with that of those randomized to receive ruxolitinib (ORR: 50.0% vs. 49.7%; BOR: 81.4% vs. 76.4%)1

Safety:

  • Incidence rates of adverse events (AEs) were comparable in all groups but grade ≥3 AEs and serious AEs (SAEs) were more prevalent in the ruxolitinib group1
  • Anemia was the most common AE among the ruxolitinib, BAT and BAT-Ruxolitnib crossover groups (ruxolitinib: 33.9%; BAT: 15.8%; BAT-Ruxolitnib crossover: 21.4%)1
  • Pneumonia was the most common SAE and contributing factor for treatment discontinuation among the 3 groups1
  • No new safety signals were reported1

 

“Ruxolitinib provided longer FFS and DOR versus BAT, demonstrating sustained efficacy for patients with steroid-refractory or dependent chronic GvHD with a consistent and manageable safety profile”

Dr. Robert Zeiser
Department of Medicine I,
Faculty of Medicine,
Medical Center,
University of Freiburg,
Freiburg, Germany

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