The FDA approval for Jakafi® (ruxolitinib) for the treatment of chronic GVHD after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years of age and older was based on data from the REACH3 study1,2
Significantly More Patients Achieved a Response With Jakafi® (ruxolitinib) at Week 24 and a Higher Response through Week 24 vs BAT1,2
- In the Jakafi Prescribing Information, efficacy was based on ORR through Week 24 (Cycle 7 Day 1)1
- 74% of patients on BAT received either extracorporeal photopheresis (ECP), mycophenolate mofetil (MMF), or ibrutinib. ORR at Week 24 was3,g,h :
29.1% (16/55; CR, 1.8%; PR, 27.3%) with ECP, 28.6% (10/35; CR, 2.9%; PR, 25.7%) with MMF, 22.2% (6/27; CR, 7.4%; PR, 14.8%) with ibrutinib
BAT, best available therapy; cGVHD, chronic graft-versus-host disease; CR, complete response; NIH, National Institutes of Health; OR, odds ratio; ORR, overall response rate; PR, partial response.
aOverall response rate was defined as the proportion of patients with complete response or partial response according to NIH consensus criteria at Week 24.2
bComplete response was defined as complete resolution of all signs and symptoms of cGVHD in all evaluable organs without additional therapies.3
cPartial response was defined as an improvement in at least one organ without progression in other organs or sites or addition/initiation of new systemic treatment.3
dLack of response was defined as disease that was unchanged, mixed response, or progression.3
eOne-sided P value, odds ratio, and 95% CI were calculated using stratified Cochran-Mantel-Haenszel test, stratifying for moderate and severe cGVHD.2
fDefined as proportion of patients who achieved complete or partial response through Week 24 (Cycle 7 Day 1).1
gThe 74% value is based on the number of patients treated with BAT (N = 158). ORRs for the remaining BATs: everolimus, 20.0% (1/5); imatinib, 25.0% (2/8); infliximab, 20.0% (1/5); low-dose MTX, 30.0% (3/10); rituximab, 16.7% (1/6); sirolimus, 28.6% (2/7).3
hREACH3 was not powered to compare ORR for Jakafi to individual BATs.
Overall Response Rates Were Higher With Jakafi® (ruxolitinib) in Patients With Moderate Disease Severity at Week 24 vs BAT3
BAT, best available therapy; cGVHD, chronic graft-versus-host disease; CR, complete response; OR, odds ratio; ORR, overall response rate; PR, partial response.
Overall Response Rates Were Higher With Jakafi® (ruxolitinib) at Week 24 Regardless of Organs Involved at Baseline vs BAT3
BAT, best available therapy; GI, gastrointestinal; OR, odds ratio; ORR, overall response rate.
aPatients with >1 affected organ were counted in each organ subgroup. Organ involvement was defined as organ score ≥1 based on the cGVHD staging criteria.3,5
Response Was More Durable With Jakafi® (ruxolitinib) vs BAT2
In the Jakafi Prescribing Information, median DOR was calculated using 2 methods:1
- Time from first response to progression, death, or new systemic therapy was 4.2 months (95% CI: 3.2, 6.7) with Jakafi and 2.1 months (95% CI: 1.6, 3.2) with BAT
- Time from first response to death or new systemic therapy was 25 months (95% CI: 26.8, not reached) with Jakafi and 5.6 months (95% CI: 4.1, 7.8) with BAT
BAT, best available therapy; cGVHD, chronic graft-versus-host disease; CR, complete response; DOR, duration of response; PR, partial response.
aDuration of response is defined as the time from first response (CR or PR) until cGVHD progression, death, or the date of change/addition of systemic therapies for cGVHD.4
bPatients who crossed over to the Jakafi treatment arm are not included in the DOR data for BAT.2
cComparison is based on the subset of patients who achieved a CR or PR at any time up to Week 24 and do not represent comparisons of randomized groups.2
Significantly Longer Median Failure-Free Survival With Jakafi® (ruxolitinib) vs BAT2
- Median FFS with Jakafi was not reached; the lower bound of the 95% CI was estimated at 18.6 months vs 5.7 months with BAT (HR, 0.370; 95% CI: 0.268, 0.510; P < 0.0001)2
- Estimated probability of FFS at 1 year was 64.0% with Jakafi (95% CI: 55.78, 71.09) and 29.6% with BAT (95% CI: 22.34, 37.23)4
- 37.2% of patients switched to Jakafi when permitted (after Week 24) and are included in the FFS assessment2
BAT, best available therapy; cGVHD, chronic graft-versus-host disease; FFS, failure-free survival; HR, hazard ratio.
aDefined as the earliest time from date of randomization to relapse or recurrence of underlying disease or death due to underlying disease, nonrelapse mortality, or addition or initiation of another systemic therapy for cGVHD.2
bDescriptive P value (ex-US only). Efficacy boundary crossed at the interim analysis (HR, 0.315; 95% CI: 0.205, 0.486; P < 0.0001). For US, the P value gives the result of the retested hypothesis at the primary analysis, following the overall hierarchical testing procedure.3
- Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.
- Zeiser R, Polverelli N, Ram R, et al; REACH3 Investigators. Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease. N Engl J Med. 2021;385(3):228-238.
- Zeiser R, Polverelli N, Ram R, et al; REACH3 Investigators. Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease [supplementary appendix]. N Engl J Med.2021;385(3):228-238.
- Data on File. Wilmington, DE: Incyte Corporation.
- Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015;21:389-401.