ABSTRACT
Introduction
The BCL2 inhibitor venetoclax has dramatically changed the treatment of chronic lymphocytic leukemia (CLL) and has introduced the concept of time-limited therapy with targeted agents.
Areas covered
This review discusses the mechanism of action of venetoclax, adverse effects, and the clinical data with this agent as identified by a selective search of clinical trials in the PubMed database. Venetoclax is FDA-approved with anti-CD20 monoclonal antibodies; however, research is ongoing evaluating its efficacy when given in combination with other agents, such as the Bruton’s Tyrosine Kinase (BTK) inhibitors.
Expert opinion
Venetoclax-based therapy is an excellent treatment option for patients interested in time-limited therapy and can be offered in both the front-line and relapsed/refractory settings. Tumor lysis syndrome (TLS) risk evaluation, preventative measures, and strict monitoring should be conducted, while these patients ramp up to target dose. Venetoclax-based therapies produce deep and durable responses with patients often achieving undetectable measurable residual disease (uMRD). This has led to a discussion of MRD-driven, finite-duration treatment approaches, although longer term data is still needed. While many patients eventually lose uMRD status, re-treatment with venetoclax remains an area of interest with promising results. Mechanisms of resistance to venetoclax are being elucidated, and research is ongoing.
List of abbreviations
CLL | = | Chronic lymphocytic leukemia |
BTK | = | Bruton’s tyrosine kinase |
TLS | = | Tumor lysis syndrome |
BCL2 | = | B-Cell lymphoma 2 |
PFS | = | Progression free survival |
OS | = | Overall survival |
DOR | = | Duration of response |
MRD | = | Measurable residual disease |
uMRD | = | Undetectable measurable residual disease |
IGHV | = | Immunoglobulin heavy chain variable |
R/R | = | Relapse/refractory |
CR | = | Complete response |
PR | = | Partial response |
CRi | = | Complete response with incomplete count recovery |
EFS | = | Event-free survival |
EOT | = | End of treatment |
ASO-PCR | = | Allele-specific oligonucleotide polymerase-chain-reaction |
FC | = | Flow cytometry |
Declaration of interest
P Bose reports no disclosures relevant to this manuscript, however, receives research support from Incyte, BMS, CTI, Kartos, Telios, Morphosys, Disc Medicine, Ionis, Blueprint, Geron, Janssen, Cogent and Sumitomo Pharma Oncology, in addition to consulting fees/honoraria from Incyte, BMS, CTI, GSK, Morphosys, Pharma Essentia, Karyopharm, Abbvie, Blueprint, Cogent, Jubilant and Novartis.
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.