Outpatient venetoclax initiation following obinutuzumab debulking in patients with high or medium tumor burden at baseline

Debulking prior to venetoclax reduces tumor burden (TB) in CLL. We report utility of outpatient obinutuzumab debulking in a Phase 3b multicenter study (NCT03406156) in patients with treatment-naïve CLL to reduce TB prior to venetoclax dose escalation. Obinutuzumab debulking (2–6 cycles) was followed by 5 cycles of obinutuzumab + venetoclax and then venetoclax monotherapy for up to 53 weeks (13 total cycles). Primary endpoints were low TB rate post-debulking and best CR/CRi rate. Overall, 94% of patients with high/medium TB achieved low TB by end of debulking (86% by end of Cycle 2), including 97% of patients with medium TB and creatinine clearance <80 mL/min. Best CR/CRi rate was 51%; undetectable MRD (10−4) rate in peripheral blood was 93%. Five patients had TEAE of tumor lysis syndrome (prior to venetoclax in 4). Obinutuzumab debulking is effective for facilitating outpatient venetoclax initiation in CLL patients with high/medium TB at baseline.