Saturday, November 22, 2025

Double refractory CLL and newly diagnosed CLL

 Ref Blood Oct 2025

CLL- 2024 ASH Frontline CLL

Newly diagnosed CLL needing rx

  • TP53 status
  • IGHV status
  • Indication for rx:
  • Cardiac hx, HTN, DOAC, bleeding hx or dual antiplatelets


Double refractory 

  • Prognosis PFS 7 months, OS 2 yr
  • 2 treatment options: pirtobrutinib and anti- CD 19  CAR- T Lisocel

1. Important to differentiate between true refractory versus exposed to these agents for limited time and or intolerance as a reason for stopping.

2. Obtain bx and mutation at progression to rule out Richter

3. Pirtobrutinib has an ORR of80% but responses last 15 months so best to start with this and plan on Lisocel. Lisocel has CR of 20%

4.  Do not discontinue BTK i immediately upon progression until there is access to the next line of treatment

5. For those who progress after CAR-T , allo SCT provided they have at least a PR

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