Prognostic Factors in Chronic Lymphocytic Leukemia

William Wierda, MD PhD: Let’s talk a little more about the prognostic factors. Nicole, who do you think of as high risk? I assume we all do somewhat similar prognostic factor work-up. I assume the information is similarly useful to you all. It gives me a good picture of the patient and what to anticipate knowing their prognostic factor profile. Given that, who are the patients you’re nervous about who are high risk and may not need treatment, but you’re going to watch them a bit closer and you have to start thinking about treatment planning eventually and what the long-term plan will be for them?

Nicole Lamanna, MD: Dr Atallah just mentioned some of them. Of course, the things we worry about are those patients with 17p deletions. We didn’t mention the IGHV molecular testing as well for those who are unmutated. These are baseline prognostic markers. In the academic world, we test for a lot more. We can talk about other molecular mutations. But it’s important for physicians who are embarking on initiating their patients on any CLL [chronic lymphocytic leukemia] therapy, whether it’s front line or in the relapse setting, to absolutely test their cytogenetics, FISH [fluorescence in situ hybridization], and their molecular IGHV status, because that may influence the type of treatments you’re going to be administering. We can talk about that—certainly for the mutation—as we go through some of the data that have come out. But for baseline, you’re going to watch your higher-risk patients who tend to be the 17p or the TP53 mutations. You may watch them a little more closely.

As many of you know, there have been many international prognostic scoring indexes and scoring systems for patients with CLL that take into consideration the stage, their TP53 status, IGHV, beta-2 microglobulin, and so on. We can use that to help categorize the patients by risk factors. It certainly shouldn’t change treatment indications. We obviously haven’t changed what we’re doing. But it gives you a higher level of suspicion based on their prognostic scoring system, where they might be, or when the time to their treatment might be based on their risk factors. It’s important to obtain these because those who still might use chemotherapy-immunotherapy might lean away from that if they’re a patient with 17p or TP53 or if they’re unmutated. Now the novel agents have come into play, so there’s far less use of chemotherapy-immunotherapy. But for those who still may use some of it, these factors are very important to test prior to starting anybody on a new therapy.

William Wierda, MD PhD: What about triggers for treatment?

Nicole Lamanna, MD: Triggers are still obviously development of cytopenias, bulky lymphadenopathy, symptomatology, weight loss, fatigue that usually is in conjunction with progressive disease. Symptoms can be a little tricky because some people will have fatigue and other symptoms that might be out of proportion to what their disease looks like. We have to weigh those as well. But typically, the development of progressive cytopenias, bulky adenopathy, and the concern for whether somebody got Richter syndrome. But as you pointed out, it’s not very common in frontline therapy.

I agree about the CT scan imaging. I do a baseline CT scan prior to starting somebody on therapy depending upon, for instance, if you’re going to use venetoclax and you want to know if anybody might be at high risk for tumor lysis syndrome. If they have bulky adenopathy internally that you might not appreciate on the outside, some of the patients, like those with 11q or 6q deletions, can hide stuff in the abdomen that don’t seem to necessarily be on the periphery. You might want a baseline CT scan prior to starting therapy. Those traditional treatment indications are still the same until we define that it might be better to start some subgroups earlier based on their genetics and that we’re changing their outcome by starting therapy earlier.

William Wierda, MD PhD: Speaking of that, we need data to justify doing that. That would require a clinical trial. I believe there are some ongoing earlier intervention clinical trials that enroll potentially high-risk patients. Does anybody want to comment on any of those ongoing trials? I see Jennifer nodding her head. Are you involved in any early intervention clinical trials?

Jennifer Woyach, MD: I’m not, but I’d be happy to put in a plug for this SWOG cooperative group study. That study is looking at early vs delayed venetoclax plus obinutuzumab. As you know, there haven’t been early intervention trials that have shown a survival advantage before. A lot of the thought behind that is, now that we know the best patients to choose, we need a therapy that’s going to eliminate disease and be relatively free of toxicity. This study is going to take patients within 1 year of their CLL diagnosis, and they have to be either high or very high risk with the CLL-IPI [CLL International Prognostic Index] criteria. This emphasizes the need for doing those prognostic studies when people are first diagnosed if they’re interested in participating in a study like this. People who have complex karyotype regardless of their IPI score would also be eligible for this study.

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