Case series: CYP Inhibition and low dose ibrutinib for steroid‐refractory chronic graft‐versus‐host disease
Abstract
Chronic graftversushost disease (cGvHD) is a complication of allogeneic stem cell transplant associated with poor quality of life and increased mortality.1 Half of treated patients develop steroidrefractory (SRcGvHD).1 Ibrutinib is an irreversible interleukin2 inducible kinase inhibitor, that blocks the proliferation of Th2 cells but not Th1 cells, the former being linked to cGvHD development.2 A multicentre study reported overall response rates (ORR) of 67% with a standard dose of ibrutinib (420 mg orally, daily, until progression) in cGvHD,3 but the 12– 512.3 USD per month cost of the drug is unpayable by our patients. Ibrutinib is metabolized by cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4), while itraconazole is an accessible CYP3A4 inhibitor that increases the plasma concentration of ibrutinib 10fold.4 Coadministering itraconazole can reduce the dosage and costs of ibrutinib by 66.6%, so this option is feasible in our limitedresource setting.5 We report the results of a case series on the preliminary efficacy and safety of CYP inhibition and low dose ibrutinib for SRcGvHD. This case series reports five consecutive patients with active SRcGvHD that received ibrutinib (140 mg orally daily, continuously) and a strong CYP3A4 inhibitor (itraconazole, 100 mg orally twice daily, continuously). They were followed weekly in the first month and then monthly. We assessed treatment response following the 2014 National Institutes of Health recommendations and quality of life with the…
How strong is the evidence?
Evidence Hub reads this as a case series, done in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health. Reported size: 42 participants or records.
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