Favourable opinion on reimbursement in “the first-line treatment of chronic lymphocytic leukaemia (CLL), solely in monotherapy or in combination with obinutuzumab: in adult patients not presenting with a 17p deletion or a TP53 mutation and ineligible for treatment with full-dose fludarabine, or in adult patients presenting with a cytogenetic status with a poor prognosis (17p deletion or a TP53 mutation)”.
What therapeutic improvement?
Therapeutic improvement in the management strategy.
Role in the care pathway?
The new data are not of a nature to modify the previous conclusions of the TC (opinion of 05/05/2021).
Clinical Benefit
Substantial
The actual benefit provided by CALQUENCE (acalabrutinib) in monotherapy or in combination with obinutuzumab is significant in the first-line treatment of chronic lymphocytic leukaemia (CLL) solely: in adult patients not presenting with a 17p deletion or a TP53 mutation and ineligible for treatment with full-dose fludarabine, or in adult patients presenting with a cytogenetic status with a poor prognosis (17p deletion or TP53 mutation).
Clinical Added Value
minor
Taking into account:
the demonstration of the superiority of the combination acalabrutinib and obinutuzumab (AO) versus chlorambucil + obinutuzumab (O-Clb) (HR = 0.10; 95% CI, [0.06; 0.17], p<0.0001), and of acalabrutinib in monotherapy versus O-Clb (HR = 0.20; 95% CI, [0.13; 0.30], p<0.0001), with regard to progression-free survival (hierarchical primary or secondary endpoint) in patients with CLL not previously treated (9.2 % with a 17p del mutation and 11.4 % with a TP53 mutation),
with a median progression-free survival not reached with the AO combination and acalabrutinib in monotherapy and a median of 22.6 months in the O-Clb group,
But in view of:
the absence of a robust comparison with ibrutinib, a comparator judged more clinically relevant than the combination chlorambucil + obinutuzumab with regard to current practice and the development of therapeutic strategy, in particular in patients presenting with a 17p deletion or a TP53 mutation,
the absence of robust data on overall survival, an endpoint that will remain exploratory due to the interruption of the hierarchical sequence upstream,
the absence of a formal conclusion on quality of life (exploratory endpoint),
the partially met medical need in first-line treatment with the available alternatives, particularly ibrutinib,
In the same way as VENCLYXTO (venetoclax) in combination with obinutuzumab, the Committee considers that CALQUENCE (acalabrutinib) in monotherapy or in combination with obinutuzumab provides minor clinical added value (CAV IV) compared to the combination chlorambucil + obinutuzumab in patients with CLL not previously treated and presenting with a 17p deletion or a TP53 mutation or in patients not presenting with a 17p deletion or a TP53 mutation and ineligible for treatment with fludarabine.
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