Reason for request
Maintenance of the favourable opinion for reimbursement as a single agent, for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL), only in patients not eligible for treatment with full-dose fludarabine.
Therapeutic improvement compared to the bendamustine / rituximab combination.
Treatment initiation is defined on the basis of the presence of symptoms and progression of the disease, in accordance with the existing Binet and Rai classifications. According to the most recent guidelines (IWCLL 2018), in general practice, patients with asymptomatic early-stage disease (Rai 0, Binet A) should be monitored without therapy unless they have evidence of disease progression or disease-related symptoms.
In patients requiring treatment, the choice depends on several factors, in particular the presence of del17p deletion and/or TP53 mutation, the patient’s general condition and the presence or otherwise of comorbidities.
In the first-line treatment of CLL, in previously untreated patients and in the absence of 17p deletion or TP53 mutation, the therapeutic strategy is as follows:
- in patients without significant comorbidities: the rituximab + fludarabine + cyclophosphamide combination (R-FC protocol) is the reference treatment.
- in patients aged over 65 years and/or those with comorbidities making them ineligible for the standard R-FC protocol, the options are ibrutinib (IMBRUVICA) as a single agent, obinutuzumab (GAZYVARO) in combination with chlorambucil (CHLORAMINOPHENE) or bendamustine (LEVACT) in combination with rituximab.
Role of the medicinal product in the care pathway
IMBRUVICA (ibrutinib) as a single agent remains a first-line therapy for CLL in patients aged over 65 years and/or those with comorbidities making them ineligible for treatment with full-dose fludarabine.
As a reminder, IMBRUVICA (ibrutinib) has no role in the management of patients eligible for fludarabine.
In the presence of a 17p deletion or TP53 mutations, IMBRUVICA (ibrutinib) as a single agent remains a first-line treatment.
The clinical benefit of IMBRUVICA remains substantial as a single agent, for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia, only in patients not eligible for treatment with full-dose fludarabine.
Clinical Added Value
the Committee considers that IMBRUVICA (ibrutinib) as a single agent provides a minor clinical added value (CAV IV) compared to the bendamustine/rituximab combination in patients not eligible for treatment with full-dose fludarabine.