Phase 1b study of ianalumab plus ibrutinib in patients with chronic lymphocytic leukemia not achieving complete response with ibrutinib

Ianalumab (VAY736) is an anti-B cell-activating factor receptor monoclonal antibody. A multicenter phase 1b dose-escalation/expansion trial evaluated the comination of ianalumab and ibrutinib among patients with chronic lymphocytic leukemia (CLL) who did not achieve a complete response (CR) with ibrutinib alone or had developed resistance mutations. Patients received intravenous ianalumab (escalation: 0.3-9.0 mg/kg; expansion: 3.0 mg/kg) once every 2 weeks and continued ibrutinib (420 mg) once daily for up to eight cycles of 28 days. Thirty-nine patients were treated (escalation: n=15; expansion: n=24). No dose-limiting toxicities were observed. At cycle 9, 38.5% of patients were in CR or CR with incomplete marrow recovery, while 43.6% achieved undetectable measurable residual disease in blood or bone marrow. These patients discontinued ibrutinib and remained off therapy for 12.1 to 24.5 months. Grade 3 or worse adverse events occurred in 41.0%, which were treatment-related in 23.1%. No on-treatment deaths were reported; one patient died because of COVID-19 during the posttreatment period. The authors conclude that the combination was well tolerated. These data support further evalations with the combination of ianalumab and BTKi for CLL.