How would you manage a CLL patient with Richters transformation that is resistant to R-CHOP with transfusion dependent cytopenias and a marrow demonstrating significant involvement by DLBCL and CLL?

Very hard situation. Probably this patient has received BTKi and venetoclax based therapies already. These cases are difficult to treat. There are no standard therapies.

Ideally, I try to take them to CAR-T therapy. The challenge is how to collect due to significant cytopenias due to extensive marrow involvement. A few cases of DLBCL in the bone marrow, I gave obinutuzumab single agent and was able to clear the marrow temporarily and long enough to collect for CAR-T. In some cases, patients bec...

Agree that this is very difficult. Combination of venetoclax + Btk inhibitor is safe and can be active in this situation. I also like the idea of anti-CD20 monoclonal antibody.

I am not aware of any data on the use of polatuzumab vedotin in Richter's, but this would be an option (+rituximab) if most of the cells in the marrow are DLBCL.