Expression of BCL2 alternative proteins and association with outcome in CLL patients treated with venetoclax

Abstract

Venetoclax, a BCL-2 inhibitor, is highly effective for the treatment of patients with chronic lymphocytic leukemia (CLL) and dependence on alternative proteins may result in resistance to BCL-2 inhibition. Patients with CLL treated with venetoclax as monotherapy at MD Anderson Cancer Center between 05/2012 and 01/2016 were included and pretreatment bone marrow was analyzed by immunohistochemistry (IHC) for BCL-W, BCL-XL, BCL2-A1 and MCL-1. Twenty-seven patients were included. BCL-W + and BCL-2A1+ was found in 15% and 7% of the patients, respectively. Both BCL-XL and MCL-1 were negative in all samples. A higher CR and longer PFS rates were observed in patients with BCL-W+ (p = .60, p = .46), BCL-2A1+ (p = .60, p = .29), and either BCL-W + or BCL-2A1+ (p = .33, p = .20), though not statistically significant. Pretreatment IHC expression of BCL-2 alternative proteins does not predict response to venetoclax in CLL, but may be a surrogate for an indolent biology. Sensitive techniques are needed to explore anti-apoptotic pathways.

Keywords:

• Chronic lymphocytic leukemia
• apoptosis
• BCL-2
• BCL-2 family

Author contributions

PS designed the study, analyzed the data and wrote the manuscript; FF analyzed the data and coauthored the mansucript; WGW, AF, MK provided clinical care to patients and coauthored the manuscript; EJS, LMSS, FV, JDK and IIW performed IHC staining and analysis and coauthored the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The study was partially supported by MD Anderson Cancer Center Support grant CA016672.