What is your preferred 1L treatment for newly diagnosed Del(17p)/TP53 mutation, high-risk CLL?

For patients with TN-CLL with TP53 aberration, the treatment options are usually based on patient factors. If a patient is a candidate for combination therapy, I prefer to treat them with uMRD-guided BTKi+BCL2i ± CD20 mAb. I only add a CD20 mAb to patients with no history of frequent infections and ...

For patients with TP53-aberrant CLL with indications for treatment, my preferred first-line treatment is with indefinite second-generation covalent BTKi therapy, e.g., acalabrutinib or zanubrutinib, which are highly effective in this setting. Fixed-duration obinutuzumab with venetoclax per CLL14 is ...

I don't have a preference for one particular treatment for del17p/TP53-mutated CLL. The conversation around 1L treatment is similar for all patients with CLL, which involves discussing fixed-duration vs. continuous treatment regimens. For patients with CLL with del17p or TP53 mutations, this discuss...

Options best supported by available data:

1. Continuous zanubrutinib or acalabrutinib. I do not add a CD20 antibody given ELEVATE-TN, which showed that adding obinutuzumab to acalabrutinib was not helpful in this patient population.
2. MRD-guided zanubrutinib plus Venetoclax per SEQUOIA Arm D.

other reaso...