Chronic Lymphocytic Leukemia Treatment Updates

Farrukh Awan, MD, University of Texas Southwestern Medical Center, spoke with the Journal of Clinical Pathways about some of the most important advancements in chronic lymphocytic leukemia (CLL) treatment over the past 10 years.

Please introduce yourself by stating your name, title, organization, and relevant professional experience.

I'm Farrukh Awan, and I'm a professor of medicine in the Department of Internal Medicine at the University of Texas (UT) Southwestern Medical Center in Dallas, Texas, where I also lead the lymphoma program and focus my clinical care on patients with CLL.

Can you discuss some of the recent advancements in CLL treatment?

The field of CLL has grown rapidly over the last 10 years or so, and we've had a number of exciting developments. It started off with a Bruton’s tyrosine kinase (BTK) inhibitor, and we had three kinds of inhibitors, which revolutionized the treatment for patients with CLL. Since then, we've come a long way.

With the first-generation molecules and drugs, we were trying to learn from them. Now, newer molecules are potentially more active, and they may have less toxicities. We have multiple generations of these molecules targeting specific proteins in the CLL cells. As a result, patients are experiencing long and durable remissions and the disease can be controlled for a long period of time. We are also exploring various combinations of these treatments in an effort to advance the field.

The biggest advancement in the field has been BTK inhibitors. We now have third generation—or some people might call them fourth generation— drugs which are effective even if the first few generations stop working for our patients. There are also BCL2 inhibitors, which are effective and can be given to patients for limited duration. This has also been a big advancement because BCL2 inhibitors give us the option of stopping treatment after a certain time point, whereas BTK inhibitors are continued indefinitely. Together, both of those treatments have significantly improved outcomes for CLL patients.

In the US and in most countries that have access to these molecules, there has been a decline in the use of chemotherapy for CLL treatment. In addition, these patients are living longer, enjoying normal lives, and are able to do things that they want to do. We’re now at another turning point where we're trying to combine these agents to come up with a strategy that allows patients to enter a nice, deep remission and stop the treatment for a certain period of time.

Following this, we are seeing that at some point down the course of the treatment, patients will experience a disease recurrence. So, the disease comes back, the resistance develops in the cancer cells, and then we have to treat them with alternative treatment.

One of the biggest advancements that has happened in the last few months has been the approval of the CAR-T cell product for patients with CLL. A small percentage of patients who have failed all approved options can have long remissions after undergoing these cellular therapy treatments.

The field keeps advancing and the prognosis for our patients has improved substantially. At some point, we hope to have a strategy that would cure or permanently eliminate the disease in a small subset of our patients. However, it's hard to quantify cures in CLL because the remission period is so long that we have to follow patients for a long period of time to definitively say that the cancer has completely been eliminated and will not come back after stopping therapy.

That's the ultimate goal that we have in the field, and we are slowly and gradually moving toward that goal. In the meantime, we are improving the lives of our patients and they are able to live long, productive lives despite having to take one or two pills a day to control the disease for a long period of time.