Novel Combination Advances in CLL - Episode 1

Reactions to Newer Therapies in CLL

Sameer Parikh, MBBS:The frontline treatment paradigm for chronic lymphocytic leukemia [CLL] has evolved over many years. We now have several new molecules, particularly small-molecule inhibitors, that have become available for the treatment of chronic lymphocytic leukemia. In particular, these agents constitute the BTK [Bruton tyrosine kinase] inhibitors, such as ibrutinib or acalabrutinib. Other medications, such as venetoclax, which is a BCL2antagonist, have also been approved for the frontline management of chronic lymphocytic leukemia. These agents have all been compared with standard of care. Chemoimmunotherapy regimens have included FCR [fludarabine, cyclophosphamide, and rituximab], bendamustine and rituximab, and chlorambucil-based regimens. And so, all of these are particularly exciting new molecules and treatments for the management of patients with CLL.

The major goals of therapy for patients who need treatment for chronic lymphocytic leukemia are the alleviation of disease symptoms and getting patients to a reasonably good remission status. In the past, the vast majority of our chemotherapy treatment regimens [lasted] approximately 6 months. After that, treatments would stop.

With the introduction of Bruton tyrosine kinase inhibitors like ibrutinib-based therapy, the paradigm shifted to more of a continuous treatment regimen, simply because ibrutinib, as a single agent or even in combination with anti-CD20 therapies, was not able to achieve deep remissions. However, now with more combination therapies, such as ibrutinib with venetoclax, or with venetoclax in combination with CD20 monoclonal antibody therapies, we are able to achieve deep remissions that allow for stopping treatment.

And so, I think we are now seeing a focus on trying to restrict the length of therapy to either 1 or 2 years of fixed duration to allow us to stop treatment once patients get to MRD [minimal residual disease]-negative status.

Transcript edited for clarity.