How Would a Harvard Oncologist Manage His Own Chronic Lymphocytic Leukemia?

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Genitourinary Oncologist and Researcher, Beth Israel Deaconess Medical Center; Instructor in Medicine, Harvard Medical School

Cancer patients often ask their doctors, “What would you do if you were me?” Here, our Curious Dr. George asks Harvard oncologist Jon Arnason, MD, how he would handle his own diagnosis of chronic lymphocytic leukemia (CLL).

Curious Dr. George:Imagine a hypothetical scenario in which, as an active clinical and research oncologist in general good health, you have lately felt less energetic than usual, have been feeling fatigued at night, and have lost some weight without dieting. You decide to visit your primary care physician for a check-up. On physical examination, she notes that you are a little pale, discovers moderately enlarged lymph nodes in the axilla and groin, and a slightly enlarged liver and spleen. She orders several lab tests. Your hematocrit is 38, hemoglobin 12, WBCs 90 000 with mostly mature lymphocytes, a proper number of granulocytes, and normal platelets. A provisional diagnosis of chronic lymphocytic leukemia (CLL) is made. How would you proceed?

Jon Arnason, MD: CLL is the most common kind of leukemia. It is a diagnosis that is often made in situations similar to the hypothetical one you present above. In addition, many patients present incidentally when laboratory testing is performed and demonstrates an incidentally elevated white blood cell count. Upon suspicion of CLL it is important to confirm the diagnosis with peripheral blood flow cytometry.

A new diagnosis of CLL can be quite distressing for patients. However, it is important to determine whether the patient is actually suffering pathology from their disease. A large percentage of patients who present with CLL will not have any active symptoms and may go for an extended period time, sometimes many years, before developing any symptoms that are attributable to their disease. In addition, a subset of CLL patients may never develop harm related to their cancer. Therefore, we do not recommend initiation of treatment if patients are asymptomatic from their CLL. Signs and symptoms that would suggest that patients require treatment include significant anemia, low platelet count, enlarged lymph nodes that are causing or about to cause symptoms, an enlarged spleen, or other systemic symptoms such as fever and weight loss that may be attributed to their disease. In addition, if the patient’s CLL-related white blood cell count doubles in less than 6 months, this suggests that the patient will imminently have symptoms and would benefit from treatment.

In the absence of the above signs or symptoms, we recommend a strategy of active surveillance. The goal of active surveillance is to identify when the patient will be about to develop symptoms and discuss treatment options at that time. At diagnosis there are number of tests that we can perform to help us predict whether a patient will have a relatively rapid progression or a more indolent course. Perhaps the most important testing to perform at diagnosis is a cytogenetic analysis. There are a number of recurrent cytogenetic abnormalities that we see with CLL. Deletion 13q is associated with a relatively good prognosis. Trisomy 12 is associated with an intermediate prognosis. Deletion 11q abnormalities are associated with large lymph nodes and a relatively more rapid progression. Finally, 17p abnormalities are associated with a poor prognosis and lack of response to traditional chemotherapeutic strategies. In addition to cytogenetic abnormalities, there is a test called IGVH mutational status. Mutations of IGVH are associated with a better prognosis than the absence of mutation.

Traditionally, CLL was treated with a combination of chemotherapeutic agents and antibody therapy. However, recent clinical studies have demonstrated that targeted therapy with oral agents and antibody treatments are more effective with less toxicity than traditional chemotherapeutic strategies. Current guidelines suggest the use of a Bruton’s tyrosine kinase inhibitor, such as acalabrutinib or zanubrutinib for continuous therapy. Alternatives include the use of the Bcl-2 inhibitor venetoclax with CD20 antibodies, potentially in addition to the use of Bruton’s tyrosine kinase inhibitors. The majority of patients will have a response to these treatments and improvement in any underlying CLL-related symptoms.

If I was diagnosed with the above findings and labs, I would not want to receive therapy. As an aging, busy clinician I am always fatigued at night, have less energy than I used to, and struggle to maintain my weight as I’m running around between clinic patients and the inpatient unit. The current data suggests that I’m not going to live any longer if I treat my CLL at diagnosis compared to at the time that I have clear symptoms. Furthermore, treatment options have significantly improved during my career, and I am hopeful that there is the potential for long term remission with some of our emerging therapies, such as CAR-T cells.

Dr. Arnason can be reached at jarnason@bidmc.harvard.edu.

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