Chronic lymphocytic leukemia (CLL) expert Dr. Seema Bhat explains the different treatment classes available for CLL patients and how the standard of care has evolved.
Dr. Seema Bhat is a hematologist at The Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Bhat here.
Dr. Bhat, when it’s time to start therapy, what types of treatments are available for CLL patients?
So, when we think about treatment for cancer, we think about chemotherapy – the conventional chemotherapy that’s associated with side effects like hair loss, nausea, or vomiting. I’m very happy to say that conventional chemotherapy is no longer the standard of care for patients with CLL. Patients who need treatment for CLL are nowadays treated with what are called, “targeted agents.”
And we have, in general, two different classes of targeted agents that have been approved for treatment for CLL. We have the BTK inhibitors, Bruton’s tyrosine kinase inhibitors, of which we have three. We have ibrutinib, we have acalabrutinib, and we have zanubrutinib. Then we have BCL-2 inhibitors, of which we currently have one approved, of which is called venetoclax. These treatments can be combined with monoclonal antibodies, which are directed towards the antigen called CD20. For example, rituximab or obinutuzumab.
Typically, venetoclax is combined with monoclonal antibody as a time-limited therapy. BTK inhibitors usually are not combined with monoclonal antibody.
What about stem cell transplant, does that fit in there?
So, stem cell transplant still has a role for treatment of patients with CLL, but it has moved down the line with such highly effective and well-tolerated oral agents available.
But, for refractory patients – what we call dual-refractory patients, we definitely are, especially in high – patients who have higher risk features, we do refer them to stem cell transplant.
And what is a dual-refractory patient, exactly?
Dual-refractory patients mean patients who have had a BTK inhibitor, be it ibrutinib, acalabrutinib, or zanubrutinib, and the disease has progressed on that. And then we give them venetoclax, which is a BCL-2 inhibitor. So, these are the two classes of targeted agents that we have available. If they have received ibrutinib, acalabrutinib, or zanubrutinib, and after that, a venetoclax, or venetoclax followed by a BTK inhibitor, and the disease has progressed on both. These patients are called dual-refractory, and currently they tend to be very resistant to whatever treatments we have available. And we looked at other modalities of treatment, be it clinical trials or stem cell transplants for that.