After prior BTKi + venetoclax and subsequent progression, how do you then choose next line therapy for high risk CLL?

In a patient having clinical progression after a fixed-duration BTKi + venetoclax, I first rule out Richter transformation and check for the acquisition of TP53 aberration and/or resistance mutations. Although the latter is rare in fixed-duration targeted therapies, it is important to rule it out. T...

If the patient received time-limited BTKi + BCL-2 and was in remission at the time of discontinuation, then frequently we consider re-treatment as either BTK monotherapy, BCL-2 + anti-CD20, or BTK + BCL-2. Many of these patients will remain sensitive to both agents. You did not ask about how long th...

The first question to ask goes back to patient preference: does the patient want to pursue fixed duration or continuous treatment? If they want another line of fixed-duration treatment, I think retreating with a venetoclax-based regimen is effective based on the available data we have. We know from ...