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

A review of the incidence of tumor lysis syndrome in patients with chronic lymphocytic leukemia treated with venetoclax and debulking strategies

“…In the Phase 3b M16-788/CLL-076 trial, low TLS risk was achieved in 20/26 (77%) patients after two cycles of debulking with obinutuzumab-bendamustine. The median decrease in lymph node size was 3 cm for obinutuzumab-bendamustine from baseline to Cycle 2; this reduced further with more cycles of debulking [24]. Ven initiated using a weekly ramp-up to target dose (cohort e Two patients were assessed after baseline.…”

“…Across studies of patients who received debulking with obinutuzumab prior to initiation of venetoclax, the aggregated number of clinical and/or laboratory TLS events was 18 in 502 patients (3.4%) [ 8 , 9 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. Two events (11.1%) were clinical (both during debulking); 13 (72.2%) were laboratory (four during debulking, three following debulking but prior to venetoclax, five during venetoclax ramp‐up, and one during combination treatment); and three (16.7%) were unclassified (timing of occurrence is not reported).…”

“…Two events (11.1%) were clinical (both during debulking); 13 (72.2%) were laboratory (four during debulking, three following debulking but prior to venetoclax, five during venetoclax ramp‐up, and one during combination treatment); and three (16.7%) were unclassified (timing of occurrence is not reported). Similarly, both clinical and laboratory TLS (one clinical [during venetoclax ramp‐up]; 10 laboratory [nine during debulking and one during venetoclax treatment]; and two unclassified [both during debulking]) were reported for 13/182 (7.1%) patients who received debulking with bendamustine (monotherapy or combined with obinutuzumab or rituximab) prior to initiation of venetoclax [ 24 , 25 , 26 , 27 , 28 ].…”

“…TLS risk reduced markedly in the Phase 2 Dutch‐Belgian Cooperative Trial Group for Hemato‐oncology (HOVON) 139/GIVe trial following debulking with two cycles of obinutuzumab monotherapy: 28% of patients were high risk, and 60% were medium risk prior to debulking; following debulking, only 1% of patients were high risk, and 15% were medium risk [ 49 ]. In the Phase 3b M16‐788/CLL‐076 trial, medium and high TLS risk (73% and 26% of patients, respectively) at baseline were mainly driven by increased ≥25 × 10 9 cells/L in 85% of patients) [ 24 ]. The median decrease in lymph node size was 0.5 cm for obinutuzumab monotherapy [ 24 ].…”

“…In the Phase 3b M16‐788/CLL‐076 trial, medium and high TLS risk (73% and 26% of patients, respectively) at baseline were mainly driven by increased ≥25 × 10 9 cells/L in 85% of patients) [ 24 ]. The median decrease in lymph node size was 0.5 cm for obinutuzumab monotherapy [ 24 ]. After two cycles of debulking therapy, low TLS risk was achieved in 56/61 (92%) patients treated with Obinutuzumab [ 24 ].…”