Monitoring CLL After Initial Diagnosis

In chronic lymphocytic leukemia (CLL), not all patients need treatment immediately after a diagnosis. Only about a third of patients do. Dr. Nicole Lamanna, a leukemia specialist at Columbia University School of Medicine, told SurvivorNet that CLL grows very slowly and some patients may be able to take an active surveillance approach for years. How often these patients are monitored depends upon their blood counts.

“The tempo of their disease is very, very important,” Dr. Lamanna said “Initially when somebody gets diagnosed, if they don’t need treatment, I tend to follow people quarterly, more or less the first year. The longer somebody has had this leukemia, and declaring that they don’t need treatment, we don’t see them as often. We start spreading out those visits, because their blood counts have been stable for years, and some of those folks are seeing me every six months. Some of them are seeing me annually.”

How a patient is treated, or monitored, will depend a lot on the results of several tests. Often, a patient is first diagnosed with CLL due to routine bloodwork. Occasionally, someone is diagnosed after seeking care for a symptom like swollen lymph nodes.

Weighing Treatment vs. Active Surveillance

“In terms of the path that patients go on when they’re first diagnosed with CLL, it can vary quite a bit.  Many patients are actually asymptomatic at the time of diagnosis, and it’s just a routine blood count that leads to the discovery of the disease,” Dr. Matthew Davids, associate director of the center for CLL at Dana-Farber Cancer Institute, told SurvivorNet. “This is often just an elevated lymphocyte count that’s not associated with any symptoms.”

Tests that go into diagnosing and planning treatment for CLL include:

• Flow cytometry of blood or immunohistochemistry of lymph tissue or bone marrow
• FISH
• DNA sequencing
• CpG-stimulate karyotype
• Physical exams
• Blood tests: CBC with differential and a comprehensive metabolic panel

“Once the diagnosis is established, there’s a variety of different molecular tests that can be sent from the blood that can help inform the prognosis for patients,” Dr. Davids explained.

“When we have the full profile of these prognostic markers, it can be very helpful in terms of determining when a patient may need treatment … For example, patients with the chromosome 17 deletion or TP53 mutation often need treatment within a few months or a year or so of diagnosis. Whereas patients who have lower risk disease like chromosome 13 abnormalities or mutated IGHV may actually go for several years, if not decades, before requiring therapy.”

Dr. Matthew Davids explains how IGHV mutations play a role in CLL prognosis.

Staging the cancer will also help doctors determine if treatment is necessary right away, and if so, what type of treatment to go with. In the U.S., the Rai staging system is commonly used for CLL. This staging system is based on how many lymphocytes are affecting the body and it’s broken up into five stages, zero, I, II, III and IV.

Staging CLL

“Early stage disease typically is manifested by an elevated lymphocyte count in the blood without any other manifestations, and we actually call this Rai stage zero CLL,” Dr. Davids explains. “When we can feel enlarged lymph nodes on the physical exam, that’s considered to be Rai stage I disease, and when we can feel an enlarged spleen or liver, we consider that Rai stage II disease.  All three of these stages, zero, one, and two, are typically considered to be early stages of CLL.

“When the disease infiltrates the bone marrow and starts to result in low red blood cell count, which we call anemia, or low platelets, which we call thrombocytopenia, these are the advanced stages, three and four, of CLL, and typically those do require treatment,” Dr. Davids added.

The five stages can also be condensed into three risk groups:

• Stage 0 is low-risk of getting worse
• Stage I and II are intermediate risk
• Stage III and IV have a high risk of progressing

For patients with disease that does require treatment, chemotherapy was once the standard approach. However, in recent years there have been incredible developments when it comes to treating CLL. Chemotherapies can now also be used with other drugs — like antibody treatments — to help treat the disease.

One of those therapies, the most common antibody treatment for CLL, targets the CD20 antigen, a protein found on B cells (which, in the case of CLL, are cancerous) in the body and summons a patient’s immune system to attack the cancer cell.

Dr. Julia Vose explains how obinutuzumab can be used to treat CLL.

The drug obinutuzumab, a CD20 antibody, is now being combined with other agents in certain treatment plans to potentially increase its effectiveness. This monoclonal antibody is usually most effective when used in combination with CLL targeted-therapy drugs, according to Dr. Julie Vose, chief of hematology and oncology at the University of Nebraska Medical Center’s Buffett Cancer Center.

Those drugs can include:

• A BTK inhibitor, which is an oral drug that targets a protein on the B cells called Bruton tyrosine kinase (BTK)
• A BCL2 inhibitor such as venetoclax, also taken orally, that targets the protein BCL2

Dr. Vose explained to SurvivorNet that when obinutuzumab is combined with these other drugs, it can be more effective at targeting and killing cancer cells.