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Safety of venetoclax rapid dose escalation in CLL patients previously treated with B-cell receptor signaling antagonists
- Source :
- Blood Adv
- Publication Year :
- 2020
-
Abstract
- Venetoclax has efficacy in patients relapsing after B-cell receptor pathway inhibitors (BCRis); however, because of the risk of tumor lysis syndrome (TLS), a 5-week dose ramp-up is required to attain the target dose. Patients relapsing after BCRis frequently have proliferative disease, requiring a faster time to target dose than this scheme allows. This limitation can potentially be overcome with rapid dose escalation (RDE). We analyzed 33 chronic lymphocytic leukemia patients who underwent venetoclax RDE after prior BTKi treatment. Median time to target dose was 9 days. Seventeen patients (52%) developed laboratory TLS, and 5 (15%) developed clinical TLS, all as a result of renal injury. TLS was seen in more patients with a higher initial tumor burden. TLS occurred at all dose levels, with most episodes occurring at the 50- and 100-mg doses. Most interestingly, a decrease in absolute lymphocyte count (ALC) from pre–venetoclax dose to 24 hours post–venetoclax dose of 10 × 103/μL was associated with an increased risk of TLS (hazard ratio, 1.32; P = .02), after controlling for venetoclax dose level. Venetoclax RDE with close in-hospital monitoring at experienced centers and in select patients is feasible. The rapidity with which ALC drops helps predict TLS and could help guide dose-escalation decisions.
- Subjects :
- Oncology
medicine.medical_specialty
Chronic lymphocytic leukemia
Receptors, Antigen, B-Cell
Antineoplastic Agents
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Antigen
Internal medicine
medicine
Humans
Receptor
B cell
Sulfonamides
Lymphoid Neoplasia
Venetoclax
business.industry
Hazard ratio
Hematology
medicine.disease
Bridged Bicyclo Compounds, Heterocyclic
Leukemia, Lymphocytic, Chronic, B-Cell
Tumor lysis syndrome
Leukemia
medicine.anatomical_structure
chemistry
030220 oncology & carcinogenesis
business
030215 immunology
Subjects
Details
- ISSN :
- 24739537
- Volume :
- 4
- Issue :
- 19
- Database :
- OpenAIRE
- Journal :
- Blood advances
- Accession number :
- edsair.doi.dedup.....a5e7a766200579fcd16dd74b31f4d703