Susan O’Brien, MD: Hello and welcome to this OncLive® My Treatment Approach program on Chronic Lymphocytic Leukemia [CLL]. I’m Susan O’Brien, associate director for Clinical Science, at the Chao Family Comprehensive Cancer Center [Orange, CA]. I'm also the medical director of the Sue and Ralph Stern Center for Clinical Trials and Research at the University of California-Irvine. I’m pleased to discuss how we approach newly diagnosed CLL patient along with my colleague, Anthony Mato, MD, MSCE, who is the director of the CLL program at Memorial Sloan Kettering Cancer Center [New York, NY]. We're going to get started by looking at a patient case. The case is a 61-year-old man who presents with fatigue and left upper quadrant fullness for about 3 months. His physical exam shows his vital signs are normal, but he has cervical adenopathy at about 2.5 cm. He has a spleen palpable 5 cm below the left costal margin. Otherwise, he looks well. If we take a look at his laboratory findings, his white cell count is 157 with predominant lymphocytes. His ALC [absolute lymphocyte count] is actually 111. He's anemic with a hemoglobin of 9.6 and his platelets are ok at 120,000. He's neutropenic with an ANC [absolute neutrophil count] of 170. Flow cytometry is consistent with CLL and that it's CD5+, CD19+ and CD23+. His molecular analysis shows that his IGHV [immunoglobulin heavy chain] gene is unmutated and he also has a deletion 17p. His beta-2-microglobulin is 3.8, so it is high, and his bone marrow biopsy shows diffuse infiltration by CLL. Anthony, what’s your impression of this case? Do you think this is a typical case? Is somewhat unusual case? What’s your thoughts?

Anthony Mato, MD, MSCE: Well, I think it’s a typical case for a patient who presents with symptoms of CLL. I would say what’s unusual is the majority of patients we see are generally asymptomatic at the time of diagnosis. So, this is a patient who has I would say, less than indolent disease or less than indolent presentation. Within a few months of the diagnosis, they have advanced stage disease. To me, it's pretty clear that this patient requires CLL directed therapy based on the physical exam findings that you highlighted. The anemia, which is probably due to marrow infiltration in the absence of some other etiology. It doesn't seem like there's anything here going for hemolysis, or we would have been told that. What's a little bit unusual or atypical in terms of the molecular genetic profile is that this patient falls into the minority of patients who have deletion 17p at the time of their initial presentation.

Susan O’Brien, MD: I agree with you. I think he's somewhat unusual for both factors that you mentioned. The first factor is that he presents with very advanced disease. I would say the best majority of the patients I see have been detected because they had a routine physical, or pre-operation blood work for knee surgery, that showed a lymphocytosis. Occasionally I see patients where they've themselves will notice lymph nodes, usually quite small. But the vast majority of the patients I see are pretty much asymptomatic at diagnosis. Now, maybe this patient is more progressed because he has high risk disease. As you said, he has a 17p deletion. In particular when those patients have an unmutated IGHV gene, they tend to progress very rapidly and probably 50% to 75% need treatment within 1 year of diagnosis. The good news as you alluded to is that this abnormality is not that common at diagnosis, it probably makes up only about 5% to 7% of patients, but it's a very common clonal evolution, so we're much more likely to see this in a relapsed refractory population.

Transcript edited for clarity.