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Efficacy and Safety of Baricitinib in Refractory Chronic Graft-Versus-Host Disease (cGVHD): Preliminary Analysis Results of a Phase 1/2 Study
Background: Chronic Graft-versus-Host Disease (cGVHD) is a multi-organ disorder characterized by immune dysregulation, impaired organ function, and decreased survival. Refractory cGVHD remains an unmet need with limited effective treatment options. Janus kinase (JAK) inhibition targeting JAK-STAT is...
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Published in: | Blood 2020-11, Vol.136 (Supplement 1), p.1-1 |
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Main Authors: | , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that cite this one |
Online Access: | Get full text |
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Summary: | Background: Chronic Graft-versus-Host Disease (cGVHD) is a multi-organ disorder characterized by immune dysregulation, impaired organ function, and decreased survival. Refractory cGVHD remains an unmet need with limited effective treatment options. Janus kinase (JAK) inhibition targeting JAK-STAT is promising in cGVHD due to this multifaceted pathway's key role in immune cell development, function, and inflammation. Baricitinib is a JAK1/2 inhibitor FDA-approved at 2 mg daily for treatment of rheumatoid arthritis, and which has shown therapeutic promise in preclinical models of GVHD. Herein, we report the preliminary analysis results of a phase 1/2 study exploring the efficacy and safety of the JAK 1/2 inhibitor baricitinib in therapy-refractory cGVHD.
Methods: Patients (pts) with therapy-refractory moderate-severe cGVHD per NIH criteria were enrolled on an NCI sponsored treatment protocol (NCT02759731). This is a phase 1/2 single center, single arm study of baricitinib starting at an oral dose of 2 mg daily, given for 28-day cycles, with intra-patient dose escalation to 4 mg daily after 3 months (mos) for a total of 12 cycles. Adverse events (AEs) were monitored and graded per CTCAEv4.3. Clinical responses were measured every 3 mos per the 2014 NIH cGVHD Response Criteria. The primary efficacy endpoint was ORR (CR+PR) at 6 mos; if PR or SD, pts were treated for up to 12 mos and monitored for 12 mos post-completion. Subjects self-report questionnaires included the Lee symptom bother scale (LSS). Peripheral blood samples were collected for pharmacokinetic and correlative studies at several time points throughout study.
Results: Twenty pts with refractory cGVHD were enrolled. Median patient age was 54 years (24-68), 55% female, 90% Caucasian. Median time from cGVHD diagnosis to study enrollment was 36.8 mos, with median baseline KPS of 80%. cGVHD NIH global score was severe in all pts (due to sclerotic skin in all except one oral), involving a median of 4 (2-6) organs, and treated with a median of 4 (2-7) lines of prior systemic therapy including ibrutinib in 3. At study enrollment, all but 3 (85%) were on concurrent systemic immunosuppression, including steroids for 12 (60%) at a median dose of 10 mg (2.5-30) prednisone daily.
ORR at 6-months was 63% (95% CI 47-87%), with durable responses seen in 7 of 8 evaluable pts at 12-mos. ORR at any time was 90% (85-100%), with median time to ORR of 1.4 mos (1.4-6.3). Organ-specific responses were seen in all involve |
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ISSN: | 0006-4971 1528-0020 |
DOI: | 10.1182/blood-2020-140392 |