Jurnal Internasional Uji coba fase 1b dari terapi kombinasi berbasis ibrutinib pada limfoma SSP rekuren / refraktori
Ibrutinib is a first-class Bruton tyrosine kinase (BTK) inhibitor and has shown the activity of a single agent in recurrent central nervous system / refractory (CNS) lymphoma lymphoma. Clinical responses are often temporary or incomplete, indicating the need for a combination therapy approach. We conducted a phase 1b clinical trial to explore sequential combinations of ibrutinib (doses of 560 or 840 mg daily) with high-dose methotrexate (HD-MTX) and rituximab in patients with CNS lymphoma (CNSL). HD-MTX is given at 3.5 g / m 2 every 2 weeks for a total of 8 doses (4 cycles; 1 cycle = 28 days). Ibrutinib was held on days of HD-MTX infusion and continued 5 days after HD-MTX infusion or after HD-MTX cleansing. Ibrutinib every day with a single agent is given continuously after induction therapy is complete until the development of the disease, intolerable toxicity, or death. We also explore sequencing the next generation of circulating tumor DNA (ctDNA) in the cerebrospinal fluid (CSF) before and during treatment. The combination of ibrutinib, HD-MTX, and rituximab was tolerated with an acceptable safety profile (no grade 5 incidence, 3 grade 4 events). No dose limiting toxicity was observed. Eleven of 15 patients continued treatment of ibrutinib after completing 4 cycles of the combination of ibrutinib / HD-MTX / rituximab. Clinical response occurred in 12 of 15 patients (80%). Continuous tumor response is associated with ctDNA clearance from CSF. This trial is listed at www.clinicaltrials.gov as # NCT02315326.