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In AMPLIFY, an all-oral, 14-month course of acalabrutinib plus venetoclax beat FCR or BR chemo-immunotherapy in fit CLL patients, offering a time-limited alternative to indefinite pills.
AMPLIFY randomised 867 fit, previously untreated patients with CLL without del(17p) or TP53 mutation to acalabrutinib plus venetoclax (AV), acalabrutinib plus venetoclax plus obinutuzumab (AVO), or investigator's choice of FCR or bendamustine-rituximab. The primary endpoint was PFS for AV versus chemo-immunotherapy. Estimated 36-month PFS was 76.5% with AV, 83.1% with AVO and 66.5% with chemo-immunotherapy (hazard ratios 0.65 and 0.42 respectively). Overall survival favoured AV, driven largely by deaths from COVID-19 in the chemo-immunotherapy arm during the pandemic. AVO produced the deepest MRD responses but more infections and neutropenia.
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.
Shares del(17p) / TP53 aberration in CLL, CLL13 / GAIA, Obinutuzumab, Chronic lymphocytic leukaemia, first treatment.
Shares CLL13 / GAIA, Obinutuzumab, Chronic lymphocytic leukaemia, first treatment, BCL-2.
Shares Acalabrutinib, Obinutuzumab, BTK (Bruton tyrosine kinase), Chronic lymphocytic leukaemia, first treatment.
Shares del(17p) / TP53 aberration in CLL, BCL-2, AbbVie (incl. ImmunoGen, Capstan), CD20.
Shares BTK inhibitor + venetoclax, fixed duration, Obinutuzumab, BTK (Bruton tyrosine kinase), Chronic lymphocytic leukaemia, first treatment.
Shares Acalabrutinib, Obinutuzumab, BTK (Bruton tyrosine kinase), Chronic lymphocytic leukaemia, first treatment.
Shares Acalabrutinib, Obinutuzumab, Chronic lymphocytic leukaemia, first treatment, AbbVie (incl. ImmunoGen, Capstan).
Shares BTK inhibitor + venetoclax, fixed duration, BTK (Bruton tyrosine kinase), Chronic lymphocytic leukaemia, first treatment, BCL-2.