Chronic lymphocytic leukemia (CLL), a cancer of B-cell lymphocytes, is the most common type of leukemia in adults. BCR signaling pathways inhibitors play an important role in the survival, proliferation, tissue adhesion, and migration of CLL cells. This finding has prompted the development of tyrosine kinase inhibitors that are directed against the B-cell receptor (BCR) pathway, including Bruton's tyrosine kinase and PI3 kinase. Another important factor in the survival of leukemic cells is played by BCL-2, an antiapoptotic protein, which is overexpressed in CLL and it is associated with tumor cell survival and resistance to chemotherapy. Venetoclax is a selective small-molecule inhibitor of BCL-2 facilitates apoptosis by binding directly to the BCL-2 protein, displacing proapoptotic proteins, and triggering mitochondrial outer-membrane permeabilization and caspase activation.
During the last 10 years treatment with the BCR signaling pathway inhibitors, ibrutinib and idelalisib, and the BCL2 inhibitor venetoclax have emerged as an effective treatment approach for B-cell malignancies, including CLL.
Treatment discontinuation with these agents due to disease progression or toxicities is a common event described in patients included in controlled clinical trials (CTs). Subsequent survival of patients who discontinue treatment with these agents is related to the reason for treatment discontinuation.
As BCR and BCL-2 inhibitors are only recently available for CLL treatment, little is known about the proportion, reasons for treatment discontinuation and outcomes of patients treated with these agents in the clinical practice. The purpose of this Italian, multicenter, retrospective/prospective observational study is to define the proportion and outcomes of patients with CLL who discontinue treatment with a BCR inhibitor or the BCL-2 inhibitor given in the clinical practice.
As BCR and BCL-2 inhibitors are only recently available for CLL treatment, little is known about the proportion, reasons for treatment discontinuation and outcomes of patients who discontinue these agents given in the clinical practice.
The purpose of this Italian, multicenter, observational study is to define the proportion and outcomes of patients with CLL who discontinue a chemo-free treatment with a BCR inhibitor (ibrutinib, idelalisib) or BCL-2 inhibitor (venetoclax) given in the clinical practice.
The identification of baseline risk factors for early treatment discontinuation could be of help in the decision-making process to address the optimal treatment choice of for unselected patients with CLL treated in the clinical practice.