Treatment and assessments
toxicity, DLTs, non-hematologic
DISEASE PROGRESSION
Patients were administered 560 mg ibrutinib once daily as a fixed dose from initial administration with concurrent venetoclax (starting with a ramp-up period to mitigate the risk of TLS). Venetoclax ramp-up consisted of four dose increases every 7 days: patients received a starting dose of 20 mg, then proceeded to 50 mg, 100 mg, 200 mg, and 400 mg venetoclax. DLTs were assessed in the first six patients during the venetoclax ramp-up period for a minimum of 5 weeks and at least 1 week of venetoclax dosing at 400 mg. Further detail pertaining to definition and criteria of DLTs (non-hematologic and hematologic) are described in the supplement. The supplement includes details on ibrutinib and venetoclax dose interruptions and reductions. Patients could continue ibrutinib plus venetoclax for a maximum of 104 weeks followed by ibrutinib monotherapy until disease progression, unacceptable toxicity, or withdrawal of consent. Patients who were high-risk for TLS (at least one lesion > 10 cm or at least one lesion > 5 cm and circulating lymphocytes) and/or baseline creatine clearance < 60 mL/min were followed closely with prophylactic measures including adequate hydration, anti-hyperuricemic agents, labs, and hospitalization [