CLL Treatment Represents ‘Very Optimistic Area’ in Research

The treatment of patients with chronic lymphocytic leukemia (CLL) has changed over the past five years to include targeted drugs and immunotherapy, which improves outcomes, remission duration and survival compared with chemotherapy.

With this shift in standard of care from chemotherapy to targeted therapies, patients with CLL and their caregivers should become aware of the more-effective treatment options available for them, said Dr. William G. Wierda, professor of medicine and section head of CLL at The University of Texas MD Anderson Cancer Center in Houston, in the CURE®’s Educated Patient® Leukemia Summit. After the presentation, CURE® spoke with Wierda about the progress that has been made in the treatment of CLL and what’s to come in this space.

CURE®: What are some of the major takeaways from your presentation?

Wierda: It's very, very unusual for us to use chemotherapy. There are certain situations where chemotherapy is contraindicated. Most of the time, patients should be talking with their doctors — if it's their first treatment or if it's a subsequent treatment —about targeted therapy and what their options are with oral targeted therapy.

There (are) two basic strategies with targeted therapy. One is the objective of getting a patient in a good, deep remission and getting them off treatment. There's an important drug that we use in that strategy called venetoclax (Venclexta). The scenario is for a fixed duration of treatment (for) one to two years with (Venclexta). A lot of times, we use additional medicines with (Venclexta) with (the) intent of getting patients in remission, and at the end of that treatment period, getting them off treatment and on observation in remission usually for several years.

The other strategy is more of a maintenance strategy. That is where we use medicines to maintain control of the disease. They're extremely effective in controlling the disease for long periods of time. It does require that patients continue on those medicines and take them daily. We have excellent disease control with that strategy as well, but it's different. Having a conversation with their doctor about these two strategies, the pluses and minuses and working with their doctor to make a decision about what the right strategy might be for a particular individual is an important conversation to have.

Are there other benefits that targeted drugs and immunotherapy offer that chemotherapy may not?

Every treatment, any medication, has side effects and toxicities, and we do see side effects and toxicities with the newer targeted therapies.

With chemotherapy, the side effects and toxicities were usually more severe. They were related to suppression of the immune system and decreases in the neutrophil count and in other blood counts, and risk for infection that's associated with that. When we used chemotherapy, we were worried about infection and those types of side effects and toxicities. Also, chemotherapy does damage the bone marrow. There are long-term effects where patients can get other cancers in the bone marrow because of their exposure to chemotherapy. The side effects and toxicities that we worry about with chemotherapy, both short term and long term, are a bit more severe than what we worry about with the targeted therapy.

The (side effects) we see with the targeted therapies are a bit more manageable and more tolerable. They have allowed us to more effectively manage disease in the older population. CLL is a disease of older people, (and) they don't tend to tolerate any medicines as well as younger people. Chemotherapy is more toxic to older people than it is to younger people. Also, the targeted therapies, we tend to see more side effects and toxicities in the older patients, but the targeted therapies are much better tolerated by older patients than chemotherapy. (Targeted therapies make) for a better treatment option and way to control the disease than we had with chemotherapy.

Is there a difference to how these treatments are administered compared with chemotherapy?

They're oral agents. We can talk about the targeted therapies in two general groups. One is the BTK inhibitors. Those are drugs like ibrutinib (Imbruvica) and acalabrutinib (Calquence). Those are broadly approved in CLL. Those are drugs that we use for the maintenance-type strategy. The other drug is (Venclexta). Those two categories of drugs have different side effects and toxicity profiles.

There are things that we monitor. For example, with the BTK inhibitors, (Imbruvica and Calquence), we do have an increased risk for bruising and bleeding. There are uncommon side effects that can be a problem like atrial fibrillation (rapid, irregular heartbeat) and hypertension (increased blood pressure). For the (Venclexta)-based therapies, (Venclexta) is an extremely potent drug in killing the leukemia cells, so much so that we can't start it at the standard dose. We have to start it at a very low dose, and we have to ramp it up over four weeks. There is a challenge with that drug in terms of this initiation and the ramp-up because we have to check the labs and make sure patients don't have problems with tumor lysis syndrome (when the contents of tumor cells are released into the bloodstream) with (Venclexta)-based therapy, but long term, when you get patients on the intended dose, it's an extremely well tolerated drug. We see very little side effects and toxicities from it. We can see neutropenia (low white blood cell count) with it, and that's usually responsive to dose reduction.

There are challenges with the new oral agents. They are a bit different, but in general, those drugs are much better tolerated by individuals who are older. When we think about older people, we think about individuals over 65 is being in the older category.

What’s on the horizon for CLL treatment?

Outcomes have remarkably improved over the recent years. Patients who have CLL who are over 65 or over 70, even if they need treatment, my expectation is for almost all patients, their lifespan won't be shortened by their diagnosis and need for treatment for CLL. Our patients are doing exceptionally well. They may need treatment, but we have very good drugs to control (and manage) their disease. And I think we're close to figuring out a cure for patients with CLL, so stay tuned. It's a very optimistic area and field (that) has been very gratifying for me to work in particularly over the last five to 10 years. There are patients who develop resistant disease, including to the targeted therapies, and we're working on new strategies for those patients where the targeted therapies aren’t working.

Clinical trials are important. And when I talk to patients, it's important to emphasize how important they are because we don't really make progress unless we have patients who are interested and willing to participate in clinical trials. If we can't do clinical trials, we can't make advances and develop the curative treatments. Investigating clinical trial options is important particularly for those individuals who are able to participate and are able to find appealing clinical trials to participate in. Things look very optimistic for patients with CLL. I'm excited to continue the work that we're doing.

This interview has been edited for clarity and conciseness.

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