Considerations and Triggers for Initiation of Treatment in a Patient with R/R CLL

An expert in treating CLL discusses potential treatment options for a patient with relapsed/refractory CLL who has been previously treated with venetoclax plus obinutuzumab.

Catherine Coombs, MD, MS: Our next question relates to what treatment I would select for this patient and why. This is a very complicated question, and I’m going to start by saying I do not think there is 1 right answer. I think the first consideration I would make is having a discussion with the patient regarding what his preferences are. Is his goal to spend more time at home, in which case perhaps reintroduction of venetoclax and the associated ramp-up may not be desirable, given the need for frequent monitoring for tumor lysis syndrome [TLS], and potential hospitalization, depending on his TLS risk stratification. If that were his goal, then perhaps a covalent BTK [Bruton tyrosine kinase] inhibitor, such as acalabrutinib or ibrutinib being the 2 FDA-approved agents, at least in April 2022, may be more desirable. The other thing I would ask him is how he did with his first go-round of therapy. Some patients cruise through that ramp-up and don’t have many adverse effects. If that was the case, then it may be desirable to the patient to repeat that regimen. I would say those are my top 2 choices for this patient. But I think there are other options that could be considered but would be less desirable, specifically being a PI3K inhibitor, which I usually would not jump to given the toxicity profile. It seems to be quite a bit less favorable compared to the other continuous monotherapy, being a continuous BTK inhibitor. Or there is chemotherapy, which I think also I would not favor, due to less efficacy and also increased toxicity, especially among older individuals.

The triggers to initiate therapy upon progression for a relapsed patient are pretty much the same as the triggers that initiate frontline therapy. These are the IWCLL [International Workshop on Chronic Lymphocytic Leukemia] guidelines for initiating therapy. This could be cytopenia, which is what is present in this patient’s case, hemoglobin of 9.2 [g/dL], and associated symptoms of fatigue. He also has thrombocytopenia, but also some other disease-related symptoms, including his low-grade fevers. This patient clearly meets an indication for therapy. I would say that myself and most other CLL-focused doctors have a bit lower of a threshold to pull the trigger on therapy upon relapse, given that there’s a bit of inevitability to therapy once a patient is already on therapy once. Of course, this can depend upon an individual clinical circumstance. But I would say in the relapsed setting, I may tend to put someone on therapy a little sooner than in the front line, given that we know at that point they’re likely going to need therapy, and it’s simply a matter of time. Especially when considering venetoclax as a patient’s therapy, I think it’s probably the better part of valor not to wait too long, given that the more disease that’s present can increase their risk for tumor lysis syndrome. Of course, this is within reason. I would never start a patient who had no symptoms and a white count of 15. But this patient in our case example is clearly past that threshold.

Transcript edited for clarity.

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