Faculty Collaboration Database

Real-world outcomes and management strategies for venetoclax-treated chronic lymphocytic leukemia patients in the United States. Haematologica 2018 Sep;103(9):1511-1517

Date

06/09/2018

Pubmed ID

29880613

Pubmed Central ID

PMC6119152

DOI

10.3324/haematol.2018.193615

Scopus ID

2-s2.0-85052872031 (requires institutional sign-in at Scopus site)   130 Citations

Abstract

Venetoclax is a BCL2 inhibitor approved for 17p-deleted relapsed/refractory chronic lymphocytic leukemia with activity following kinase inhibitors. We conducted a multicenter retrospective cohort analysis of patients with chronic lymphocytic leukemia treated with venetoclax to describe outcomes, toxicities, and treatment selection following venetoclax discontinuation. A total of 141 chronic lymphocytic leukemia patients were included (98% relapsed/refractory). Median age at venetoclax initiation was 67 years (range 37-91), median prior therapies was 3 (0-11), 81% unmutated IGHV, 45% del(17p), and 26.8% complex karyotype (≥ 3 abnormalities). Prior to venetoclax initiation, 89% received a B-cell receptor antagonist. For tumor lysis syndrome prophylaxis, 93% received allopurinol, 92% normal saline, and 45% rasburicase. Dose escalation to the maximum recommended dose of 400 mg daily was achieved in 85% of patients. Adverse events of interest included neutropenia in 47.4%, thrombocytopenia in 36%, tumor lysis syndrome in 13.4%, neutropenic fever in 11.6%, and diarrhea in 7.3%. The overall response rate to venetoclax was 72% (19.4% complete remission). With a median follow up of 7 months, median progression free survival and overall survival for the entire cohort have not been reached. To date, 41 venetoclax treated patients have discontinued therapy and 24 have received a subsequent therapy, most commonly ibrutinib. In the largest clinical experience of venetoclax-treated chronic lymphocytic leukemia patients, the majority successfully completed and maintained a maximum recommended dose. Response rates and duration of response appear comparable to clinical trial data. Venetoclax was active in patients with mutations known to confer ibrutinib resistance. Optimal sequencing of newer chronic lymphocytic leukemia therapies requires further study.

Author List

Mato AR, Thompson M, Allan JN, Brander DM, Pagel JM, Ujjani CS, Hill BT, Lamanna N, Lansigan F, Jacobs R, Shadman M, Skarbnik AP, Pu JJ, Barr PM, Sehgal AR, Cheson BD, Zent CS, Tuncer HH, Schuster SJ, Pickens PV, Shah NN, Goy A, Winter AM, Garcia C, Kennard K, Isaac K, Dorsey C, Gashonia LM, Singavi AK, Roeker LE, Zelenetz A, Williams A, Howlett C, Weissbrot H, Ali N, Khajavian S, Sitlinger A, Tranchito E, Rhodes J, Felsenfeld J, Bailey N, Patel B, Burns TF, Yacur M, Malhotra M, Svoboda J, Furman RR, Nabhan C

Author

Nirav N. Shah MD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Antineoplastic Agents
Antineoplastic Combined Chemotherapy Protocols
Bridged Bicyclo Compounds, Heterocyclic
Disease Management
Drug Resistance, Neoplasm
Female
Humans
Leukemia, Lymphocytic, Chronic, B-Cell
Male
Middle Aged
Recurrence
Sulfonamides
Survival Analysis
Treatment Outcome
Tumor Lysis Syndrome