Targeting of Bcl-2 might, therefore, be a promising option, especially in patients with specific or adverse AML features.

The agents, which target different critical pathways in the malignant B cell – Bruton tyrosine kinase (BTK) by ibrutinib and B-cell lymphoma 2 protein (BCL2) by venetoclax – significantly improved outcomes compared with historical controls.

Participants were randomly assigned to receive either daily oral venetoclax for up to 2 years or intravenous bendamustine on days 1 and 2 of each 28-day cycle for six cycles, with both groups also receiving rituximab for the first 6 months.

One study investigated the addition of the BCL-2 inhibitor venetoclax to hypomethylating agents in AML patients aged 65 years and older, while the other evaluated the combination of inotuzumab ozogamicin – an anti-CD22 antibody bound to the cytotoxic agent calicheamicin – and low-intensity chemotherapy in ALL patients aged at least 60 years.

They each received the orally bioavailable inhibitor of apoptosis regulator Bcl-2 venetoclax at a starting dose of 20 mg daily, increasing to 400 mg daily by week 5.

A total of 49 participants were given the BCL2 inhibitor venetoclax daily with a stepwise escalation to the target doses of 200–600 mg, after which monthly rituximab was initiated, at a dose of 375 mg/m 2 in the first month and 500 mg/m 2 in months 2–6.

Stimulation of T cells by 4-1BBL, its cognate ligand expressed on dendritic cells, results in proliferation and upregulation of the antiapoptotic proteins Bcl-2-like protein 1 (Bcl-xL) 79 , Bcl-2-related protein A1 (Bfl-1) 79 , 80 and CASP8 and FADD-like apoptosis regulator (c-FLIP) 80 , which protect T cells from activation-induced cell death 79 , 80 , 81 , 82 .