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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.
In plain words · TP53 is the 'guardian of the genome', broken in half of all cancers. Fixing it directly has so far defeated every attempt, so drugs exploit what its loss makes cancers depend on.
Showing the target this term concerns: TP53.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
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.
Shares CLL-IPI (chronic lymphocytic leukaemia prognostic index), AMPLIFY, CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients, Chronic lymphocytic leukaemia, first treatment.
Shares AMPLIFY, AMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patients, SEQUOIA, Chronic lymphocytic leukaemia, first treatment.
Shares The p53 network (guardian of the genome), Richter transformation of chronic lymphocytic leukaemia, Cytogenetics and FISH, TP53.
Shares CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients, Chronic lymphocytic leukaemia, first treatment, Chronic lymphocytic leukaemia.
Shares 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, Chronic lymphocytic leukaemia, first treatment, Chronic lymphocytic leukaemia.
Shares AMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patients, Chronic lymphocytic leukaemia, first treatment, Chronic lymphocytic leukaemia.
Shares Relapsed or refractory chronic lymphocytic leukaemia, Chronic lymphocytic leukaemia, first treatment, Chronic lymphocytic leukaemia.
Shares SEQUOIA, Mantle cell lymphoma, Chronic lymphocytic leukaemia.