Venetoclax Consolidation in High-Risk Cll Treated With Ibrutinib for ≥1 Year Achieves a High Rate of Undetectable MRD

Authors

Philip A Thompson
Michael J Keating
Alessandra Ferrajoli
Nitin Jain
Christine B Peterson
Naveen Garg
Sa A Wang
Jeffrey L Jorgensen
Tapan M Kadia
Prithviraj Bose
Naveen Pemmaraju
Nicholas J Short
William G Wierda

Publication Date

7-1-2023

Journal

Leukemia

DOI

10.1038/s41375-023-01901-4

PMID

37138019

PMCID

PMC11913176

PubMedCentral® Posted Date

3-17-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Patients receiving ibrutinib for CLL rarely achieve undetectable measurable residual disease (U-MRD), necessitating indefinite therapy, with cumulative risks of treatment discontinuation due to progression or adverse events. This study added venetoclax to ibrutinib for up to 2 years, in patients who had received ibrutinib for ≥12 months (mo) and had ≥1 high risk feature (TP53 mutation and/or deletion, ATM deletion, complex karyotype or persistently elevated β2-microglobulin). The primary endpoint was U-MRD with 10−4 sensitivity (U-MRD4) in bone marrow (BM) at 12mo. Forty-five patients were treated. On intention-to-treat analysis, 23/42 (55%) patients improved their response to CR (2 pts were in MRD + CR at venetoclax initiation). U-MRD4 at 12mo was 57%. 32/45 (71%) had U-MRD at the completion of venetoclax: 22/32 stopped ibrutinib; 10 continued ibrutinib. At a median of 41 months from venetoclax initiation, 5/45 patients have progressed; none have died from CLL or Richter Transformation. In 32 patients with BM U-MRD4, peripheral blood (PB) MRD4 was analyzed every 6 months; 10/32 have had PB MRD re-emergence at a median of 13 months post-venetoclax. In summary, the addition of venetoclax in patients treated with ≥12mo of ibrutinib achieved high rate of BM U-MRD4 and may achieve durable treatment-free remission.

Keywords

Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Adenine, Bridged Bicyclo Compounds, Heterocyclic, Neoplasm, Residual, Antineoplastic Combined Chemotherapy Protocols, Piperidines, Sulfonamides

Published Open-Access

yes

Recommended Citation

Thompson, Philip A; Keating, Michael J; Ferrajoli, Alessandra; et al., "Venetoclax Consolidation in High-Risk Cll Treated With Ibrutinib for ≥1 Year Achieves a High Rate of Undetectable MRD" (2023). Faculty, Staff and Student Publications. 5728.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5728