It can be a head-turning experience for a patient with newly diagnosed CLL to be told, “You have cancer, but we do not need to treat it right away.” The idea of watchful waiting may be quite foreign to them. While some individuals are grateful that they do not require therapy immediately, others may find this to be incredibly anxiety provoking. This strategy goes against messages from the lay media about how early detection and early treatment save lives. While this may be true for many other cancers, it is not true for CLL at this time.

In most cases, I obtain molecular prognostic testing at diagnosis, including IGHV mutation status, fluorescence in situ hybridization (FISH), and TP53 mutation analysis. Other practitioners may elect to wait until the patient needs therapy, and either approach is acceptable. The IGHV analysis provides an indication of how quickly the disease is likely to progress, and the FISH analysis predicts response to therapy, once needed. Using these assessments, I can provide an estimate for the patient about how their disease is likely to behave.

TP53 is a variable that I think is commonly misunderstood. Getting both FISH and TP53 sequence analysis is important to identify those patients who might have mutations or deletions. The FISH assay detects the deletion of a segment of DNA that corresponds to the patient’s TP53. At the sequence level, TP53 mutations largely are seen in those who already have 1 copy of TP53 deleted. However, approximately 1 in 3 patients with aberrant TP53 functioning have a mutation at the sequence but no 17p deletion. If you rely only on FISH, you can miss some of those patients with TP53 mutations, so testing for both can be important.

Both TP53 mutation and complex karyotype testing are areas in which there seem to be considerable variability between practices. Many investigators who spend a lot of time studying and treating CLL will test for complex karyotype because it provides additional information, but none of these tests are free of charge, and I think that using them carefully and judiciously is a reasonable approach. Because of the variability in the process of karyotyping, it is important to use a reputable reference laboratory. If the cells are stimulated too much, that can drive them toward a complex karyotype that may or may not actually be clinically relevant. I do not necessarily obtain complex karyotyping for every patient, but I am increasingly performing more of this testing in my practice.

We still do not have any evidence that there is a high-risk group (eg, IGHV-unmutated disease and 17p deletion) for whom initiating therapy prior to conventional International Workshop on Chronic Lymphocytic Leukemia treatment criteria is indicated. This may change with time, and I believe that we are developing therapeutics that may have the ability to alter that trajectory—but we are not there yet.