A 79-Year-Old Man With Relapsed Chronic Lymphocytic Leukemia - Episode 4
Jeff Sharman, MD: After first-line treatment, what is the trigger to start second-line therapy in CLL? Again, the same indications that we talked about for first-line therapy are true in second-line therapy: rapid progression of lymphocyte count, symptomatic bulky lymph nodes, emergence of bone marrow dysfunction. Those are true in both the front-line and relapsed refractory setting.
When you’re considering treatment for patients with therapy in the relapsed setting, that’s going to be strongly influenced by what they received in the first-line setting. For a patient such as this with the deletion of 17p, you don’t have a whole lot of options. They would include venetoclax in combination with rituximab, similar to the MURANO study, or idelalisib and rituximab. Because this patient has significant chronic kidney disease, the risk of tumor lysis is quite high.
Furthermore, we know that if there’s a sweet spot for PI3 kinase inhibitors, it tends to be in that older population with significant medical comorbidities. I think this is a great patient for whom to consider idelalisib-rituximab. It wouldn’t be wrong to pick rituximab with venetoclax; however, it would need to be very carefully monitored for risk of tumor lysis, likely even admitting that patient to the hospital for the first several dose levels. With some 79-year-old patients, that’s a difficult proposition to make, so I think in this particular case starting idelalisib-rituximab would be very reasonable.
We’re asked to comment on the patient’s status at the current time. Does his risk status matter? The answer is yes. We’re probably going to get about a year and a half median progression-free survival for idelalisib-rituximab. The question will be what to do next.
In a 79-year-old, perhaps other medical comorbidities may limit survival beyond that, but this is a patient where if the next therapy is going to be venetoclax-based treatment, I don’t want that patient to develop bulky adenopathy before transitioning to that therapy because the risk of tumor lysis may be too great.
Regarding next treatment options, there are clinical trials in this space looking at BTK inhibitors that may work even after a prior BTK inhibitor has stopped working. LOXO305 is one potential option, and ARQ 531 is another BTK inhibitor that could work in this space. If the patient is able to travel for a clinical trial, that might be an option.
Transcript edited for clarity.
Case: A 79-Year-Old Man With Relapsed Chronic Lymphocytic Leukemia