Ruxolitinib (RUX) Vs Best Available Therapy (BAT) in Patients with Steroid-Refractory/Steroid-Dependent Chronic Graft-Vs-Host Disease (cGVHD): Primary Findings from the Phase 3, Randomized REACH3 Study
▪ BACKGROUND Standard first-line treatment of cGVHD includes systemic corticosteroids; however, about 50% of patients (pts) are steroid refractory or dependent (SR/D) and require additional treatment. The best second-line therapy option has not yet been defined. RUX, an oral JAK1/2 inhibitor, was su...
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Veröffentlicht in: | Blood 2020-11, Vol.136 (Supplement 1), p.22-24 |
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Sprache: | eng |
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BACKGROUND
Standard first-line treatment of cGVHD includes systemic corticosteroids; however, about 50% of patients (pts) are steroid refractory or dependent (SR/D) and require additional treatment. The best second-line therapy option has not yet been defined.
RUX, an oral JAK1/2 inhibitor, was superior to BAT in SR acute GVHD (aGVHD) in a phase 3 study (REACH2). Here we present the primary analysis of the REACH3 study (NCT03112603), a phase 3, open-label, randomized study evaluating RUX vs BAT in pts with SR/D cGVHD.
METHODS
Eligible pts were ≥ 12 years old, had received allogeneic hematopoietic cell transplant, and had developed moderate or severe SR/D cGVHD. Pts transitioning from aGVHD to cGVHD without tapering steroids were excluded. Pts treated with JAK inhibitors for aGVHD were allowed if they achieved complete response (CR) or partial response (PR) and had been off JAK inhibitor treatment for ≥ 8 weeks prior to cycle 1 day 1. Those treated with ≥ 2 prior lines of systemic therapy for cGVHD in addition to corticosteroids ± calcineurin inhibitors (CNI) were ineligible.
Pts were randomized (1:1) to RUX 10 mg bid or investigator-selected BAT (10 options) and were treated for 6 cycles (cycle = 28 days). Pts continued receiving their regimen of corticosteroids ± CNI. Viral prophylaxis and antibiotics were allowed as needed for infection prevention and treatment. Addition or initiation of a new BAT was allowed only after lack of response, intolerable toxicity, or cGVHD flare and was considered treatment failure. Crossover from BAT to RUX was allowed on or after cycle 7 day 1 (C7D1) in pts who did not achieve or maintain CR/PR, developed toxicity to BAT, or had a cGVHD flare.
The primary endpoint was overall response rate (ORR) at C7D1. ORR was defined as the proportion of pts achieving CR or PR, per NIH consensus criteria. Key secondary endpoints were failure-free survival (FFS; defined as time to the earliest of recurrence of underlying disease, start of new systemic treatment for cGVHD, or death) and improvement in symptoms based on change in the modified Lee symptom score (mLSS; 0 [no symptoms] to 100 [worst symptoms]) at C7D1. An mLSS responder was defined as having achieved a ≥ 7-point reduction from baseline in the total symptom score. The primary and key secondary endpoints were α-controlled via an overall hierarchical testing procedure.
RESULTS
A total of 329 pts were randomized to RUX (n = 165) or BAT (n = 164). Baseline characteristics were ba |
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ISSN: | 0006-4971 1528-0020 |
DOI: | 10.1182/blood-2020-137694 |