del(17p) / TP53 aberration in CLL
A del(17p) deletion or TP53 mutation means loss or damage of the p53 safety gene in CLL. These patients should never get chemotherapy; they need BTK inhibitors or venetoclax, usually continuously.
Present in ~5-10% at diagnosis and up to 40% at relapse. Chemoimmunotherapy is ineffective; continuous BTK inhibition (SEQUOIA arm C, 5-year PFS 72% with zanubrutinib) or venetoclax-based therapy is standard; fixed-duration regimens have shorter remissions in this group. Excluded from AMPLIFY, so acalabrutinib-venetoclax is not labelled for del(17p)/TP53.
AMPLIFY delivered the first all-oral, fixed-duration doublet for front-line CLL and supported its approval, giving fit patients a way to avoid both chemotherapy and years of continuous BTK inhibitor. It does not settle whether a doublet or triplet is best, or how AV compares with venetoclax-obinutuzumab. Patients with TP53 aberration were excluded and still need different strategies.
CLL14 established the first chemotherapy-free, fixed-duration regimen for front-line CLL and made MRD-guided thinking mainstream in the disease. Patients get a year of treatment and then a treatment-free period rather than indefinite therapy. The choice today is between fixed-duration venetoclax combinations and continuous BTK inhibitors, with no proven survival difference.
MURANO made fixed-duration venetoclax the standard for relapsed CLL and showed that stopping therapy after a deep response is safe for most patients. It also established MRD at end of treatment as a practical guide to who is likely to stay in remission. Retreatment with venetoclax at relapse appears feasible.
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not linked directly; found by shared links- ProductRituximab
Shares Caution: chemoimmunotherapy in del(17p)/TP53 CLL, SEQUOIA, MURANO: two years of venetoclax plus rituximab versus chemo-immunotherapy in relapsed CLL, Mantle cell lymphoma.
- PairingBTK inhibitor + venetoclax, fixed duration
Shares SEQUOIA, AMPLIFY, AMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patients, Chronic lymphocytic leukaemia.
- TermIGHV mutational status
Shares AMPLIFY, CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients, Chronic lymphocytic leukaemia.
- ProductBendamustine
Shares MURANO: two years of venetoclax plus rituximab versus chemo-immunotherapy in relapsed CLL, Mantle cell lymphoma, Chronic lymphocytic leukaemia.
- ProductZanubrutinib
Shares Caution: chemoimmunotherapy in del(17p)/TP53 CLL, SEQUOIA, Mantle cell lymphoma, Chronic lymphocytic leukaemia.
- ProductAcalabrutinib
Shares AMPLIFY, AMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patients, Mantle cell lymphoma, Chronic lymphocytic leukaemia.
- CompanyAbbVie (incl. ImmunoGen, Capstan)
Shares MURANO: two years of venetoclax plus rituximab versus chemo-immunotherapy in relapsed CLL, AMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patients, CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients, Mantle cell lymphoma.
- ProductVenetoclax
Shares Caution: chemoimmunotherapy in del(17p)/TP53 CLL, SEQUOIA, AMPLIFY, MURANO: two years of venetoclax plus rituximab versus chemo-immunotherapy in relapsed CLL.