Patient with CLL (del 13q, IGHV unmutated), history of autoimmune hemolytic anemia s/p rituximab, started ven/obin for frontline treatment 5 years ago. He has continued on venetoclax monotherapy at the end of his one year of treatment with ven/obin. Peripheral blood MRD has been positive since 3 years ago, initially at 0.04% and over the past few months, has risen to 1.6% months ago and 3.2%. Patient would like to lengthen the duration he can be in remission prior to needing his next line of therapy (with a BTK inhibitor). Is it reasonable to try obin at this time to achieve MRD negativity (in the absence of meeting iwCLL criteria for needing next line of therapy)? Would you stop the venetoclax at this time or continue it until he needs his next line of treatment?

CLL Specialist

Absolutely reasonable to give another course of obinu while continuing the venetoclax and repeat mrd testing in a few months to see if you are making any progress. I don’t see too much downside assuming he is tolerating/has tolerated this regimen well. If he’s progressing further, I would stop both ven and obinu but if he’s responding I’d be open to continuing both. I have on occasion continued BTKi beyond progression with the thought that it’s still giving some disease control and withdrawing it will cause more rapid progression. I think the same argument can be made here, though not evidence-based.