Case series: CYP Inhibition and low dose ibrutinib for steroid‐refractory chronic graft‐versus‐host disease.

Keywords: chronic graft versus host disease; CYP; ibrutinib; itraconazole; low dose EN chronic graft versus host disease CYP ibrutinib itraconazole low dose 573 576 4 04/20/23 20230501 NES 230501 Chronic graft-versus-host 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 steroid-refractory (SR-cGvHD).[1] Ibrutinib is an irreversible interleukin-2 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. Shorter ibrutinib cycles until progression are feasible, (i.e., patient 1 received only 2 months of ibrutinib-itraconazole therapy and the response lasted 6.5 months). This case series reports five consecutive patients with active SR-cGvHD that received ibrutinib (140 mg orally daily, continuously) and a strong CYP3A4 inhibitor (itraconazole, 100 mg orally twice daily, continuously). [Extracted from the article]