Complex testing offers answers and guidance about a lifelong illness


For patients with chronic lymphocytic leukemia (CLL) — the most common leukemia in adults — advanced testing can not only provide valuable information about their disease state, but peace of mind in the face of a progressive, incurable illness. Oftentimes, however, complex molecular and genetic tests to identify biomarker cues about disease trajectory and treatment intolerance are not performed, putting patients at risk for unmet expectations and unsatisfactory outcomes.

According to data from the inform CLL Registry, the largest U.S.-based, prospective registry of CLL patients receiving treatment, less than 30% of patients undergo molecular testing to stratify their risk of disease progression. Among patients already receiving treatment, data highlight low rates of biomarker testing, which is useful for identifying mutations that hinder therapy response.

This scattershot testing is apparent to Mayo Clinic hematologists who specialize in managing CLL.

“Breast cancer, lung cancer, colon, and prostate cancers are more common type of cancers seen in the community, but CLL is not as common as these types of cancers,” says Mayo Clinic hematologist Wei Ding, M.B.B.S., Ph.D. “Many of the complex molecular tests may not be easily accessible or be very familiar to community oncologists. These molecular tests that help predict the evolving nature of CLL disease are critically important for patients to plan for their future lives. As these tests are often not routinely offered in the community, patients come to Mayo Clinic to seek an answer. They appreciate that we share the features of their disease with them and develop a long-term model of care for them.”

Patients who turn to Mayo Clinic and Mayo Clinic Laboratories for another take on their illness have access to a comprehensive slate of CLL tests, including fluorescence in situ hybridization (FISH), molecular tests (including IGHV and TP53 somatic mutation analyses), and flow cytometry methodologies, all which meet the requirements of the National Comprehensive Cancer Network and the CLL-International Prognostic Index.

Comprehensive testing yields detailed results

Because many patients diagnosed with CLL do not initially present with symptoms necessitating treatment, it’s essential that prognostic tests are completed at the initial consultation to provide a more predictable picture for their disease course.

For all patients, including asymptomatic individuals requiring a “watch and wait” approach, FISH testing and molecular mutation tests to identify prognostic markers can denote different tiers of risk, Dr. Ding says. “When an asymptomatic patient comes into the office and gets their diagnosis, they are extremely anxious about how the disease is going to behave. This is a very important counseling point for that patient. Highly complex testing guides us to classify that patient into whatever risk they are and make projections based on the survival curve. This helps us to think about how to monitor the patient and how they will progress even before the therapy point.”

Having results that highlight disease trajectory is vital to patients who badly want information on their prognosis and monitoring plan, Dr. Ding says. “We typically follow these patients for a long time and the frequency of follow up is guided by testing.”

Dr. Ding says concrete information about disease trajectory helps inform choices. “It’s important for patients so they can make decisions such as whether they should be changing their life’s course or quitting their stressful job. Testing helps to inform decisions from both the physician and patient side.”

Advanced testing guides treatment

Often patients with CLL don’t experience symptoms until years after their initial diagnosis. These can include fatigue, weight loss, night sweats, fever and/or chills, enlargement of lymph nodes, upper abdominal pain due to splenic enlargement, and low blood counts. When worsening symptoms do require treatment, molecular testing, such as TP53 and CLL FISH assays, can identify genetic deviations that affect patient response to certain therapies.

“Even though novel therapies tend to work on everyone, there are differences in how well patients respond and in the side effects,” Dr. Ding says. “When we consider the options of therapy for a patient, the decision is typically made based on risk factors, patient preferences and comorbidities, such as if the patient is elderly or has heart disease or other disease. We tend to treat with a different type of therapy than others who don’t have those issues.”

By performing TP53 sequencing studies and IGHV mutation analysis, along with CLL FISH, which are not always available at lower volume laboratories, providers get the most complete picture of genetic abnormalities. For instance, mutations identified through TP53 sequencing are associated with poor outcomes and patients may be resistant to standard chemotherapy and chemoimmunotherapy regimens.

Informed with a complete picture of how patients will respond to treatment, providers can prescribe the most appropriate therapy — sometimes experimental therapies — or point patients to clinical trials, Dr. Ding says.

It’s important to consider how best to acquire those detailed results in areas or instances when advanced testing isn’t possible, Dr. Ding says. “At Mayo Clinic, we are very subspecialized and consider ourselves to be more of an expert in CLL testing. We are at an academic center and we strive to be better.”

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Robin Huiras-Carlson

Robin Huiras-Carlson is a senior marketing specialist at Mayo Clinic Laboratories and a Mayo Clinic employee since 2015. Her writing focuses on specialty testing, innovation, and patient-focused initiatives.