How would you treat a fit patient with a history of relapsed CLL who now presents with Richter transformation s/p autologous anti-CD19 chimeric antigen receptor (CAR) T-cells?

This is very challenging and essentially in a data-free zone. There are some data on off-label use of axi-cel for Richter, and liso-cel technically has a label for Richter. Results appear encouraging, but treatment and outcomes after CART failure are unknown. I would consider everything possible – clinical trials (preferred if available and eligible), immunotherapy, BTKi, BCL2i, chemotherapy, radiation, transplant, etc.

If clonality is known and the Richter is clonally unrelated to the underlying...