Presenters: Caroline M. Mejías-De Jesús, PharmD, BCOP, Beth Israel Deaconess Medical Center, Boston, MA; Lauren McGinty, PharmD, BCOP, Beth Israel Deaconess Medical Center, Boston, MA
Co-Authors: Verona Abdelmeseh, PharmD, BCOP, Northshore University Hospital, Manhasset, NY; Ajoy Dias, MD, MRCP, Beth Israel Deaconess Medical Center, Boston, MA
BACKGROUND: The use of venetoclax has benefited numerous patients and has changed the treatment landscape across several hematologic malignancies. However, it brings several challenges, including prolonged hospitalizations for slow dose ramp-ups with frequent monitoring. There are limited data on the safety of escalating doses more rapidly than is described in initial trials and in the prescribing information, but doing so has the potential to benefit patients and the healthcare system by decreasing the number of admissions and lengths of stay associated with treatment initiation.
OBJECTIVE: To evaluate the safety and feasibility of rapid dose escalation of venetoclax in patients with hematologic malignancies.
METHOD: A retrospective chart review was conducted for adults in the inpatient setting with hematologic malignancies who received rapid ramp-ups of venetoclax that deviated from the prescribing information recommendations between January 2018 and June 2022 at Beth Israel Deaconess Medical Center. The safety end points included the proportion of patients who had tumor lysis syndrome (TLS) per the Cairo-Bishop criteria and other adverse events (AEs) during the ramp-up. Feasibility was measured by the proportion of patients achieving the target 400-mg dose or an alternative stable dose. Descriptive statistics were calculated.
RESULTS: A total of 22 patients received a rapid dose escalation of venetoclax. The median age at venetoclax initiation was 68.5 years (range, 51-87 years). The most common indications included mantle-cell lymphoma (N = 6; 27.3%), relapsed/refractory chronic lymphocytic leukemia (CLL; N = 5; 22.7%), and de novo CLL (N = 4; 18.2%). A total of 10 (52.6%) patients received B-cell receptor pathway inhibitor therapy immediately before receiving venetoclax. All patients started the ramp-up in the inpatient setting with TLS monitoring. The most common schedule (9.1%) was 20 mg on day 1 of week 1, 50 mg on days 2 and 3 of week 1, 100 mg on days 4 through 7 of week 1, 200 mg on days 1 through 7 of week 2, and then 400 mg daily. All but 1 patient received appropriate TLS prophylaxis. In all, 19 (86.4%) patients completed the ramp-up and achieved the 400-mg target dose. A total of 3 (13.6%) patients achieved a stable dose of 200 mg as a result of drug–drug interactions or AEs. The median time to a target or stable dose was 14 days (range, 4-39 days). Laboratory TLS occurred in 1 (4.5%) patient at the 20-mg dose, which resolved without intervention; 2 (9.1%) patients at the 50-mg dose, 1 of which resolved without intervention and the other required treatment with rasburicase and sevelamer; and 1 (4.5%) patient at the 200-mg dose, which resolved without intervention. No clinical TLS was reported. Other AEs included anemia (45.5%), thrombocytopenia (36.4%), and neutropenia (31.8%). No discontinuation of venetoclax occurred during the ramp-up.
CONCLUSION: Rapid dose escalation of venetoclax initiated with close inpatient monitoring was tolerated with minimal TLS.
- Davids MS, Shadman M, Parikh SA, et al. A multicenter, retrospective study of accelerated venetoclax ramp-up in patients with relapsed/refractory chronic lymphocytic leukemia. Abstract presented at the American Society of Hematology Annual Meeting 2020; Abstract 3145. https://ash.confex.com/ash/2020/webprogram/Paper139885.html.
- Koenig KL, Huang Y, Dotson EK, et al. Safety of venetoclax rapid dose escalation in CLL patients previously treated with B-cell receptor signaling antagonists. Blood Adv. 2020;4:4860-4863.
- Davids M, Jones J, Eradat H, et al. Modified venetoclax dose ramp-up in select high-risk patients with chronic lymphocytic leukemia (CLL) with progression after B-cell receptor pathway inhibitors (BCRi). Clin Lymphoma Myeloma Leuk. 2017;17(suppl 2):302. Abstract CLL-101.