Why Chemotherapy Is No Longer the Standard for Most CLL Patients

BTK inhibitors have transformed CLL care by helping patients live longer while avoiding many of the side effects associated with traditional chemotherapy.

“Rather than in the old days when we targeted with cytotoxic chemo — the stuff that makes your hair fall out and makes you feel sick — these actually inhibit a pathway that’s critical to the cancer cells and less critical to normal cells,” Dr. Yair Levy, a Dallas-based hematologist at Baylor University Medical Center, explains to SurvivorNet.

Targeting the Cancer Instead of Healthy Cells

Traditional chemotherapy works by attacking rapidly dividing cells throughout the body. While this approach can destroy cancer cells, it also damages healthy cells that divide quickly, such as those in the hair follicles, digestive tract and bone marrow. That’s why chemotherapy often causes side effects like hair loss, nausea and low blood counts.

BTK inhibitors work differently. These drugs block a signaling pathway known as the B-cell receptor pathway, which CLL cells depend on to grow and survive.

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“When we interrupt that signaling, we disrupt things that are vital for these cancer cells for growth, survival and proliferation,” Dr. Levy says.

BTK inhibitors target the leukemia more selectively by interfering with a process that CLL cells rely on far more than normal cells.

A Major Leap Beyond Chemotherapy

According to Dr. Levy, this difference in how BTK inhibitors work represents one of the biggest advances in CLL treatment in recent decades.

“They’re not cytotoxic chemotherapy,” he says. “They don’t just target rapidly dividing cells.” Unlike chemotherapy, BTK inhibitors do not “try to cause breaks in DNA” or “prevent DNA synthesis,” he explains. Those mechanisms are “the mainstay of how these cytotoxic chemotherapies work.”

Instead, they interrupt the signals that cancer cells rely on to grow and survive.

“The cancer cells are much more dependent on this pathway than our normal cells,” Dr. Levy explains. “So we do get a more targeted killing of the cancer cells as opposed to normal cells. That also lends itself to a better tolerability profile.”

Because BTK inhibitors cause less damage to healthy tissues, many patients experience fewer debilitating side effects than they would with chemotherapy.

Treatment Can Now Continue for Years

Another important advantage is how doctors administer these therapies. Chemotherapy is typically administered for a limited period because the cumulative damage to healthy cells eventually outweighs the benefits.

“You can’t just give people cytotoxic chemotherapy forever because it would not be very well tolerated,” Dr. Levy says. BTK inhibitors, however, are designed for long-term use.

“People can just take a pill every day — or sometimes a pill twice a day — and they can be on it for many, many years at a time,” he says.

For many patients, these oral medications keep the leukemia under control while allowing them to continue working, traveling and participating in everyday activities.

‘Quality of Life Remains High’

Perhaps the biggest change has been the impact on survival. Dr. Levy says the advances in targeted therapies have dramatically changed what it means to receive a CLL diagnosis.

“I’m just so excited that my patients are just not dying of CLL anymore,” he says. “No one’s lived forever yet, but they’re dying with CLL, not from CLL, which is a very important distinction.”

Equally important is that many patients are able to maintain a good quality of life during treatment.

“Therapies tend to be relatively well tolerated,” Dr. Levy says. “So quality of life remains high, which is incredibly important because the worst thing in life is not dying — the worst thing in life is a long and unpleasant life. Thankfully, we’ve managed to get therapies that prolong life, and they do it in a very, very tolerable, non-invasive way.”

Research Continues to Push the Field Forward

Despite the dramatic progress, researchers continue working to improve treatment options for patients whose disease becomes resistant to current therapies.

“We do still have some unmet needs,” Dr. Levy says, noting that some patients eventually become refractory to both BTK inhibitors and another class of targeted drugs known as BCL-2 inhibitors. Doctors can use these therapies together or in sequence to achieve deep remissions that may eventually allow some patients to stop treatment.

New Options When CLL Stops Responding

Even so, the outlook continues to improve. New approaches — including CAR T-cell therapy and other investigational treatments— are expanding the options available for patients whose CLL returns or stops responding to treatment.

“We do have CAR T[-cell] therapies,” Dr. Levy says, “and we also have some very promising drugs that are in development.”

As research advances, physicians hope even more patients will benefit from treatments that not only extend survival but also preserve quality of life — quite a shift from the days when chemotherapy was the only option.

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