SAVE, Safe Accelerated Venetoclax Escalation: A phase Ib study of obinutuzumab plus venetoclax with daily ramp-up in CLL

While venetoclax (VEN)-based regimens are highly effective for patients with chronic lymphocytic leukemia (CLL), initiation is complex, due to the requirement of a 5-week dose ramp-up used to mitigate the risk of tumor lysis syndrome (TLS). We report the results of the first prospective study of VEN initiation using an accelerated inpatient dose ramp-up in CLL. Forty patients were treated, including 15 (37.5%) with relapsed or refractory disease and 13 (32.5%) with medium (27.5%, n=11) or high (5%, n=2) TLS risk at enrollment. All except one (97.5%) received obinutuzumab in combination with VEN. All patients completed an accelerated daily VEN ramp-up from 20 mg to 400 mg in the inpatient setting. None had clinical TLS. One (2.5%) patient with Bruton tyrosine kinase inhibitor-refractory CLL and high TLS risk developed laboratory TLS after the 200 mg dose of VEN, which normalized within a day with a 1-day dose hold and supportive care. The median inpatient time was 7 days. In intent-to-treat analyses of efficacy at 3 months, the overall response rate was 78.0%. Our data support the feasibility of accelerated VEN ramp-up in select patients in experienced centers and warrant further exploration of this approach in broader clinical settings. NCT04843904.