IMBRUVICA (ibrutinib) - Chronic lymphocytic leukaemia (CLL)

New indication.

Key points

Favourable opinion on reimbursement, in combination with venetoclax, in the treatment of adult patients with chronic lymphocytic leukaemia (CLL) not previously treated and not presenting with a 17p deletion and/or a TP53 mutation, and ineligible for treatment with full-dose fludarabine. 

Unfavourable opinion on reimbursement in the other situations of the MA extension namely, in combination with venetoclax, in the treatment of adult patients with CLL not previously treated presenting with a 17p deletion or a TP53 mutation and in patients not presenting with a 17p deletion or a TP53 mutation and eligible for treatment with fludarabine.

What therapeutic improvement?

Improvement in therapeutic strategy.

Role in the care pathway?

In the light of the data available from the GLOW study which demonstrated the superiority of the medicinal product IMBRUVICA (ibrutinib) in combination with venetoclax compared to the combination chlorambucil + obinutuzumab (O-Clb) in terms of progression-free survival, procurement of minimal residual disease and complete response rate, IMBRUVICA (ibrutinib) in combination with venetoclax, is an additional first-line treatment option for CLL in patients not presenting with a 17p deletion or a TP53 mutation and ineligible for treatment with fludarabine.

The current data do not allow IMBRUVICA (ibrutinib) in combination with venetoclax to be positioned relative to therapeutic alternatives such as IMBRUVICA (ibrutinib) in monother-apy, VENCLYXTO (venetoclax) in combination with obinutuzumab, and CALQUENCE (acalabrutinib) in combination or not with obinutuzumab in the absence of comparative data.

In patients with CLL not previously treated presenting with a 17p deletion or a TP53 mutation and in patients not presenting with a 17p deletion or a TP53 mutation and eligible for treatment with fludarabine, the role of IMBRUVICA (ibrutinib) in combination with venetoclax is not established, due to lack of data.

The Committee recalls that in compliance with the SmPC “appropriate clinical evaluation of cardiac history and cardiac function should be performed prior to initiating treatment with IMBRUVICA. Patients should be carefully monitored during treatment for signs of clinical deterioration of cardiac function, and clinically managed. Consider further evaluation (e.g. ECG, echocardiogram), as indicated, for patients in whom there are cardiovascular concerns"  (see section 4.2 of the SmPC).

Specific recommendations

As a reminder, with regard to VENCLXYTO (venetoclax), the Committee recommends a systematic assessment of the risk of occurrence of tumour lysis syndrome (tumour mass best appraised by a CT scan, lymphocytosis, estimation of glomerular filtration), before beginning the treatment. Preventive measures such as the use of urate-lowering drugs, hyperhydration (oral or intravenous) and biological monitoring of patients during the first days of treatment must be implemented systematically. The appropriateness of hospitalisation must be assessed on a case-by-case basis according to the initial assessment of the risk of tumour lysis syndrome.