REACH3 Was a Randomized, Open-label, Multicenter, Phase 3 Study of Jakafi^® (ruxolitinib) vs BAT in Patients With Steroid-Refractory cGVHD^1,2

• In the Jakafi Prescribing Information, efficacy was based on ORR through Week 24 (Cycle 7 Day 1)¹

BAT, best available therapy; BID, twice daily; cGVHD, chronic graft-versus-host disease; CNI, calcineurin inhibitor; GI, gastrointestinal; mLSS, modified Lee Symptom Scale; NIH, National Institutes of Health; ORR, overall response rate; REACH, Ruxolitinib in PatiEnts with RefrACtory Graft-Versus-Host Disease After Allogeneic Stem Cell Transplantation

^aCrossover from BAT to Jakafi was permitted on or after Week 24 if patients progressed, had a mixed or unchanged response, developed toxicity to BAT, or experienced a cGVHD flare. 61 patients crossed over to Jakafi after Week 24. 72% of those who crossed over remained on Jakafi longer than 24 weeks.^2,4

^bBest available therapy was chosen by the investigator prior to randomization. Options included ibrutinib, extracorporeal photopheresis, low-dose methotrexate, mycophenolate mofetil, rituximab, everolimus, sirolimus, imatinib, or infliximab, or pentostatin.¹

^cDefined as the proportion of patients with complete response or partial response at Week 24.²

^dDefined as the earliest time from date of randomization to relapse or recurrence of underlying disease or death due to underlying disease, non-relapse mortality, or addition or initiation of another systemic therapy for cGVHD.²

^eDefined as a ≥7-point reduction from baseline in total symptom score on the scale, which measures the symptoms of chronic GVHD on a scale of 0 to 100, with higher scores indicating worse symptoms.²

^fOrgan involvement at baseline for all patients (N = 329): skin (71.1%), mouth (60.8%), eyes (57.4%), lungs (42.9%), joints and fascia (27.4%), liver (24.9%), GI tract (22.8%), genital tract (9.4%), missing (0.3%). Organ involvement was based on NIH consensus staging criteria at screening. A score of ≥1 was counted as organ involvement. Patients with missing assessments of single organs were counted as having no organ involvement for the organ assessed.³

^gSteroid-refractory disease was defined as lack of response or disease progression after ≥1 week of prednisone 1 mg/kg/day or disease persistence without improvement after ≥4 weeks of prednisone >0.5 mg/kg/day or 1 mg/kg/every other day. Steroid-dependent cGVHD was defined as increase in prednisone dose to >0.25 mg/kg/day after 2 unsuccessful attempts to taper the dose. Failure to taper is defined as re-escalation of corticosteroid dose to >2 mg/kg/day methylprednisolone or inability to taper methylprednisolone dose to <1 mg/kg/day for a minimum of 7 days.^3,4

REACH2 Study Population

REACH2 enrolled a population with Grades II–IV acute graft-versus-host disease (GVHD) in all affected organs.

aGVHD, acute graft-versus-host disease.

^aAll patients in REACH2 were located outside the US.^1
bAn increase in the steroid dose to ≥2 mg/kg/d methylprednisolone or prednisone equivalent or inability to taper the dose to <0.5 mg/kg/d methylprednisolone or prednisone equivalent for a minimum of 7 days.^1
cSeven patients with Grade 0 or Grade I aGVHD were randomized in error and were flagged as having a protocol deviation.¹

References

1. Zeiser R, von Bubnoff N, Butler J, et al. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. N Engl J Med. 2020;382(19):1800-1810.

2. Zeiser R, von Bubnoff N, Butler J, et al. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease [supplementary appendix]. N Engl J Med. 2020;382(19):1800-1810.

Patients Treated With Jakafi® (ruxolitinib) Had Significantly Greater Improvements in Patient-Reported Modified Lee Symptom Scale Scores vs Control Therapy

mLSS, Modified Lee Symptom Scale; OR, odds ratio.

Patients experienced a mean (standard deviation) modified Lee Symptom Scale (mLSS) reduction of 9.26 (13.34) points with Jakafi and 2.40 (10.43) points with control therapy.³

^a Lee symptom scale is a 30-item, 7-domain, self-administered scale for detecting changes in cGVHD symptom status. REACH3 study used a modified version that focuses on symptom severity and has a shortened recall period of 1 week.^4
b mLSS response was defined as percentage of patients with a ≥7 point decrease in TSS from baseline to 6 months (Cycle 7 Day 1).^1
c Statistically significant at the primary analysis. At the interim analysis (N = 196), patients receiving Jakafi had a numerically but not significantly higher mLSS responder rate (19.6% vs 8.1%; OR, 2.80; P = 0.0151) than those receiving control therapy.²

Reference

1. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.

2. Zeiser R, Polverelli N, Ram R, et al. [placeholder for final publication]

3. Data on File. Wilmington, DE: Incyte Corporation.

4. Zeiser R, Polverelli N, Ram R, et al. [placeholder for supplementary appendix]

Median Failure-Free Survival With Jakafi^® (ruxolitinib) Compared With Control Therapy

Median failure-free survival (FFS) with Jakafi was 5 months and was one month with control therapy.¹

• The cumulative incidence of cancer relapse or progression at 18 months was 13% with Jakafi and 19% with control therapy¹
• The cumulative incidence of non-relapse-related death at 18 months was 49% with Jakafi and 51% with control therapy¹

• Jakafi has not been demonstrated to improve survival outcomes in steroid-refractory aGVHD
• REACH2 was not designed to compare survival probabilities between Jakafi and control therapy

Failure-free survival data were not statistically significant.

FFS, failure-free survival; HR, hazard ratio.

^aDefined as time from randomization to relapse or progression of hematologic disease, non–relapse-related death, or addition of new systemic therapy for aGVHD. Competing risk was the onset of chronic GVHD.^1
bHazard ratio is for relapse or progression of hematologic disease, non–relapse-related death, or addition of new systemic therapy for acute GVHD.¹

Reference

1. Zeiser R, von Bubnoff N, Butler J, et al. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. N Engl J Med. 2020;382(19):1800-1810.

Responses With Jakafi by Day 28 Across All Grades Studied

In a subgroup analysis of overall response rate at day 28, all 13 patients with Grade II acute GVHD (aGVHD) at baseline responded to treatment with Jakafi, and over 40% of patients in both the Grade III or IV aGVHD groups responded.¹

ORR, overall response rate.

Reference

1. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.

FDA approval for Jakafi^® (ruxolitinib) for the treatment of steroid-refractory aGVHD was based on the data from the REACH1 study^1-3

• Although the adverse event data reported in REACH2 is informative, the risk information as described in the Full Prescribing Information for Jakafi should be considered when making prescribing decisions

References

1. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.

2. Jagasia M, Perales MA, Schroeder MA, et al. Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial. Blood. 2020;135(20):1739-1749.

3. Zeiser R, von Bubnoff N, Butler J, et al. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. N Engl J Med. 2020;382(19):1800-1810.