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The first-in-human study of venetoclax, the BCL-2 blocker that grew from a discovery at the Walter and Eliza Hall Institute in Melbourne. Four in five people with relapsed CLL responded.
A phase 1 dose-escalation study (NCT01328626) of daily oral venetoclax in relapsed or refractory chronic lymphocytic leukaemia or small lymphocytic lymphoma, led from the Royal Melbourne Hospital, the Walter and Eliza Hall Institute and Peter MacCallum Cancer Centre with AbbVie and Genentech. 56 patients received one of eight doses from 150 to 1,200 mg a day; 60 more were treated in an expansion cohort with a weekly stepwise ramp-up to 400 mg. Most had several previous treatments and 89 percent had poor prognostic clinical or genetic features.
Clinical tumour lysis syndrome occurred in 3 of 56 patients in dose escalation, with one death; after the ramp-up schedule was introduced it occurred in none of the 60 in the expansion cohort. 92 of 116 patients (79 percent) responded, including 71 to 79 percent in subgroups with fludarabine resistance, 17p deletion or unmutated IGHV; 20 percent had complete remission, 5 percent without minimal residual disease by flow cytometry. Estimated 15-month progression-free survival at 400 mg was 69 percent.
It showed that blocking BCL-2 could clear chronic lymphocytic leukaemia that other drugs had not, and the ramp-up dosing it introduced to prevent tumour lysis is still how venetoclax is started.
Shares John F. Seymour, Walter and Eliza Hall Institute of Medical Research, Peter MacCallum Cancer Centre, Chronic lymphocytic leukaemia.
Shares Walter and Eliza Hall Institute of Medical Research, Peter MacCallum Cancer Centre, Venetoclax.
Shares Venetoclax, Chronic lymphocytic leukaemia.
Shares John F. Seymour, Venetoclax, Chronic lymphocytic leukaemia.
Shares Venetoclax, Chronic lymphocytic leukaemia.
Shares Venetoclax, Chronic lymphocytic leukaemia.
Shares Venetoclax, Chronic lymphocytic leukaemia.
Shares Venetoclax, Chronic lymphocytic leukaemia.
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