IMBRUVICA - LLC en association (ibrutinib)
Reason for request
Unfavourable opinion for reimbursement for IMBRUVICA in combination with obinutuzumab in the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL).
The therapeutic indications are 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 of CLL treatment depends on several factors: the presence of del17p deletion and/or TP53 mutation (associated with an unfavourable prognosis due to a low response rate and a short duration of response to standard chemo-immunotherapy treatments), the patient’s general condition and the presence or otherwise of comorbidities.
- In the absence of a del17p mutation or TP53 mutations:
o In patients without significant comorbidities: as first-line therapy for CLL, a rituximab + fludarabine + cyclophosphamide combination (R-FC protocol) is the reference treatment,
o In elderly patients and/or those with comorbidities making them ineligible for “full-dose” standard R-FC protocols, the options are as follows:
- IMBRUVICA (ibrutinib), orally, as a single agent.
- Anti-CD20 monoclonal antibody and chemotherapy combinations:
- GAZYVARO (obinutuzumab) + chlorambucil (G-Clb protocol)
- MABTHERA (rituximab) + chlorambucil or bendamustine (B+R protocol).
- In the presence of a del17p mutation or TP53 mutations, IMBRUVICA as a single agent is the reference treatment.
Role of the medicinal product in the care pathway
Given the methodological limitations of the ILLUMINATE trial, and in the absence of comparative data versus ibrutinib as a single agent, the Committee deems that IMBRUVICA in combination with obinutuzumab has no role in the care pathway.
The clinical benefit of IMBRUVICA (ibrutinib) in combination with obinutuzumab is insufficient to justify its funding by the French national health insurance system in the indication extension “IMBRUVICA in combination with obinutuzumab is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL)”.