A retrospective observational study of rapid titration of venetoclax (VEN) in patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).

Abstract

e19018 Background: CLL and MCL can present with rapid disease progression that requires quick control. VEN is an oral, small-molecule inhibitor of BCL-2 that requires careful dose titration to avoid TLS. However, standard outpatient titration of VEN takes 29 days to reach max dose, with the low doses achieving little disease control. A common practice at our site is to rapidly titrate VEN to 100mg within 1 week with hospitalization for careful TLS monitoring and management. We present the safety and outcomes of 39 identified patients treated as such. Methods: The rapid VEN titration plan was: VEN 20mg x 2 days, 50mg x 2 days, then 100mg daily with q6-q8 hour monitoring of TLS labs plus ongoing IV hydration and allopurinol with or without rasburicase per clinical judgment. Most patients were treated in such manner if TLS did not occur. Clinically stable patients were typically discharged after 2 days of VEN 100mg, then continued weekly outpatient dose escalation to the 200mg and then the 400mg dose levels. If a patient was progressing on a Bruton's Tyrosine Kinase inhibitor, the inhibitor was often given concurrently with the early doses of VEN. Results: Patient characteristics are listed in the table. 23% (5 of 22) of patients with CLL and 35% (6 of 17) of patients with MCL had laboratory TLS (Howard SC, NEJM2011). In the patients with CLL, 2/5 were low risk for TLS, and in the patients with MCL, 3/6 were low risk for TLS. Only 4.5% (1 of 22) of CLL patients and no MCL patients had clinical TLS (Grade 2 creatinine elevation). In that specific patient, considered low risk for TLS, the elevated creatinine did not recover but was subsequently deemed secondary to Richter’s transformation involving the kidneys. No unexpected toxicity was observed outside of those typically associated with VEN and anti-CD20 antibody, when used. The mean number of days to reach 100mg was 6.5 days (quartile [Q] 1:5d; Q3: 10d), and the mean number of days to reach the planned VEN target dose was 18.8 with range (Q1:14d; Q3: 25d). Sixty-four percent of patients achieved the 400mg dose level. Conclusions: This single-institution retrospective analysis highlights the low rate of clinical TLS when using VEN with rapid titration in a controlled environment for high-risk patients needing rapid disease control. However, lab TLS occurred in low-risk patients treated in this manner, necessitating hospitalization despite low risk. No unexpected or additional toxicity was observed. [Table: see text]