Chronic lymphocytic leukemia (CLL) is a type of cancer affecting the immune system. In a person with CLL, the infection-fighting part of white blood cells, known as B cells, don’t function properly.

Currently, no drug or other therapy has been able to cure CLL, but researchers are working on developing new drugs in the hope of making a cure possible.

To cure CLL, a treatment will have to wipe out all of the cancer cells and prevent the cancer from ever coming back or relapsing. So far, the challenge has been that a small number of cancer cells often remain in the body after treatment. This is called minimal residual disease (MRD).

Because CLL is a slow-growing cancer, some people won’t need to start treatment for many years after diagnosis. In people whose cancer does spread, treatments can help them achieve long periods of remission, during which there is no sign of cancer in the body.

Just a few years ago, people with CLL had no treatment options beyond chemotherapy. In recent years, new combinations of different treatment methods, including chemoimmunotherapy. targeted therapy, and bone marrow and stem cell transplants, are changing the outlook of CLL.

These treatments dramatically extend the survival times for people with this cancer, helping them live longer in remission.

Researchers have been experimenting with new combinations of chemotherapy and immunotherapy (chemoimmunotherapy, or CIT) that work better than either treatment alone.

Some of these combinations, like FCR, are helping people live disease-free for much longer than ever before. FCR, a standard treatment for younger and fitter patients for over a decade, is a combination of the chemotherapy drugs fludarabine (Fludara) and cyclophosphamide (Cytoxan), plus the monoclonal antibody rituximab (Rituxan).

A 2016 study of 300 young and fit people with CLL who have a mutation in their IGHV gene found that more than half survived for 13 years disease-free on FCR. The study suggests that FCR can potentially cure some of the people with this type of gene mutation.

For people with CLL over the age of 65, doctors have preferred to treat them with the bendamustine-rituximab (BR) combination rather than FCR because of its lower toxicity.

But a 2018 study found that ibrutinib alone was more effective in prolonging the progression-free survival rate of older patients than treatment with BR. When compared with the combination of ibrutinib plus rituximab, there’s no significant difference in their effectiveness.

CAR T-cell therapy is a special kind of immune therapy that uses your own modified immune cells to fight cancer.

First, immune cells called T cells are collected from your blood. Those T cells are genetically modified in a lab to produce chimeric antigen receptors (CARs) — special receptors that bind to proteins on the surface of cancer cells.

When the modified T cells are placed back into your body, they seek out and destroy cancer cells.

CAR T-cell therapy is approved for a few other types of non-Hodgkin’s lymphoma but not for CLL. Ongoing clinical trials are studying whether this type of therapy could produce longer remissions or even a cure for CLL.

A 2022 case study shows complete remission for a decade in two people with CLL who received CAR T-cell therapy.

Targeted drugs like idelalisib (Zydelig), ibrutinib (Imbruvica), and venetoclax (Venclexta) go after substances that help cancer cells grow and survive. Even if these drugs can’t cure the disease, they may help people live much longer in remission.

Recent randomized controlled trials have compared the efficacy of the second-generation BTK inhibitor zanubrutinib with the standard first-line treatment, ibrutinib, as well as combination therapies such as bendamustine plus rituximab.

An analysis of these trials suggests that zanubrutinib is as promising a therapy as ibrutinib in helping those with CLL to continue to live without disease progression. It also suggests that this second-generation BTK inhibitor can be significantly better than immunochemotherapy in contributing to progression-free survival (PFS).

Other ongoing clinical trials are looking into many different combination treatments.

One 2019 study involved people with a median age of 75 who hadn’t been treated for CLL and had coexisting conditions. They were treated with a combination of venetoclax (targeted drug) and obinutuzumab (monoclonal antibodies/immunotherapy), and this combination was shown to be more effective than chlorambucil-obinutuzumab in contributing to PFS. As many as 63% of those treated with fixed-duration venetoclax-obinutuzumab remained without a PFS event (disease progression or death) 4 years after the treatment.

Allogenic stem cell transplantation is currently the only treatment that offers the possibility of a cure for CLL. With this treatment, you get very high doses of chemotherapy to kill as many cancer cells as possible.

Chemo also destroys the healthy blood-forming cells in your bone marrow. Afterward, you get a transplant of stem cells from a healthy donor to replenish the cells that were destroyed.

The problem with stem cell transplants is that they’re risky. The donor cells could attack your healthy cells. This is a serious condition called graft-versus-host disease.

Having a transplant also increases your risk of infection. Also, it doesn’t work for everybody with CLL. Stem cell transplants improve long-term disease-free survival in about 40% of people who get them.

As of now, no treatment can cure CLL. The closest thing we have to a cure is a stem cell transplant, which can be risky and only helps some people survive longer.

New treatments in development could change the future for people with CLL. Immunotherapies and other new drugs are already extending survival. In the near future, new combinations of drugs and other types of therapies may help people live longer.

The hope is that one day, treatments will become so effective that people will be able to stop taking their medication and live a full, cancer-free life. When that happens, researchers will finally be able to say that they’ve cured CLL.