CLL-076: Phase 3b Study to Evaluate Debulking Regimens Prior to Initiating Venetoclax Therapy in Untreated Patients with Chronic Lymphocytic Leukemia

Background/Aims Bcl-2 inhibitor venetoclax (VEN) has demonstrated efficacy in patients with chronic lymphocytic leukemia (CLL). As VEN induces rapid cell death, patients with medium- to high tumor burden (TB) are at greater risk for tumor lysis syndrome (TLS). We explore tumor debulking prior to outpatient VEN initiation. Methods This phase 3b trial enrolled untreated adults with CLL/SLL without 17p deletion, having medium-to high TB. Patients received at least 2 cycles (C), or a maximum of 6 cycles of debulking therapy (Obinutuzumab [G] ± bendamustine [B]). Once achieved low TB, VEN was started with VEN+G initially, then VEN monotherapy. Primary endpoints were reduction in TB after every 2 C of debulking, and IWCLL response rates. Results As of 12/2/2019, 110 patients were included; 76 received G and 34 G+B for debulking. Majority were Conclusions Most patients achieved low TB at C2 of debulking with G±B prior to VEN ramp-up. AE of TLS was reported in 1 patient during VEN phase. Similar Gr ≥3 AEs were observed during VEN phases regardless of debulking agents. Debulking reduced TB and may facilitate outpatient VEN initiation. Abstract was previously published at EHA25.