Am I at Risk for Developing Progressive CLL?

Research Identifies Likelihood of CLL Progression in Patients

Researchers at nine institutions in the United Kingdom have found a way to predict whether patients with chronic lymphocytic leukemia (CLL) will develop more progressive forms of the blood cancer — a discovery that could help guide decisions about when to start treatment.

The research findings, published in Nature Communications in January 2021, identified a genetic tendency to develop progressive CLL (meaning the leukemia has caused significant changes to blood counts or other serious symptoms) by examining blood samples of patients with the disease.

"The study has demonstrated that CLL patients often possess the same genetic tendencies, and as such we can analyze the non-cancerous cells of prospective patients to predict the likelihood of future diagnosis,” Dr. David Allsup, a senior lecturer at Hull York Medical School in the United Kingdom, said in a press release.

He added: “The study also allows us to move towards a more personalized diagnosis of leukemia and adapt our approach for patients based on the likelihood of them developing aggressive symptoms.”

Watch and Wait or Treatment?

Most people diagnosed with CLL are in their 70s, according to the Mayo Clinic. But CLL may not cause any symptoms for years, despite the leukemia cells being present in the blood. In fact, approximately 70% of newly diagnosed CLL patients do not need immediate treatment, according to the CLL Society. Those patients are actively observed by their healthcare team, a status referred to in laymen’s terms as “Watch and Wait.”

“Usually when we first meet a patient and we're starting to talk to them and you say, ‘Listen, we don't want to do anything,’ people think that's crazy, right?” said Dr. Ian Flinn, a CLL expert from Tennessee Oncology, in a Patient Power interview. “We know from studies that have been done over decades that patients who are treated early don't necessarily do better than patients who are watched and waited until they have progression of disease, signs and symptoms of the CLL that's causing issues for them.”

He added: “It's not that our therapies aren't good, they're actually excellent right now, they're just not better early than when you use them later.”

Still, it's important that patients with CLL are treated as soon as their disease becomes active, Dr. Richard Furman, director of the CLL Center at Weill Cornell Medical College in New York, told Patient Power, “so, you don't have those long-term issues of damaging the bone marrow and the immune system that could really lead to long-term complications.”

A Challenging Prognosis

Treatment for symptomatic CLL has been transformed by highly effective chemoimmunotherapy regimens, such as obinutuzumab (Gazyva) in combination with chlorambucil, and targeted therapies like ibrutinib (Imbruvica), a Bruton tyrosine kinase (BTK) inhibitor, and venetoclax (Venclexta), which targets the BCL2 protein.

However, identifying those patients at risk of progression remains challenging. While the recent discovery is not a cure for CLL, being able to identify the disease early could boost survival.

“Emerging evidence suggests that early treatment for patients at high risk of developing progressive CLL could significantly delay the onset of symptomatic leukemia and improve survival,” said study co-author Professor James Allan, a professor of cancer genetics at Newcastle University Centre for Cancer, in the press release.

Dr. Allsup echoed his colleague.

"Not only does the research inform us if patients have the genetic tendency to develop progressive CLL,” he said, “but it also enables us to determine whether or not a patient's CLL will require treatment in the future or not. That way, we are able to keep a close eye on the patients with a high risk and have treatment options available as soon as they are required."