VENCLYXTO (vénétoclax) - LLC en association avec l’obinutuzumab

Key points

Approval of reimbursement, in association with obinutuzumab, for the treatment of previously untreated patients with chronic lymphocytic leukaemia (CLL), only in the presence of a 17p deletion and/or TP53 mutation or for patients with no 17p deletion or TP53 mutation and ineligible for fludarabine-based treatment.

Disapproval of reimbursement in the other marketing authorisation contexts, namely for patients with no 17p deletion or TP53 mutation and eligible for fludarabine-based treatment.

Therapeutic improvement?

Therapeutic improvement with respect to the chlorambucil + obinutuzumab association for treatment.

Role in therapeutic strategy?

According to ESMO 2021 guidelines, the French group FILO’s 2020 guidelines, and IWCLL 2018 guidelines, the therapeutic indications are defined according to the presence of symptoms and progressive nature of the disease (as per the existing Binet and Rai classifications). In routine practice, patients with asymptomatic early-stage (Rai 0, Binet A) disease should be monitored without any treatment, unless they have signs of disease progression or disease-related symptoms. In cases of psychological impact or complications from the disease, particularly tumoral syndrome and/or cytopenia, treatment is required.

For patients requiring a first-line treatment, the choice of this treatment is dependent on a number of parameters: age, health state of the patient, presence of comorbidities or not, and cytogenetic status (presence of del(17p) and/or TP53 mutation, IGVH mutation status):

• In the presence of a TP53 mutation and/or del(17p),
  • IMBRUVICA (ibrutinib) monotherapy is currently the conventional treatment
  • CALQUENCE (acalabrutinib), as monotherapy or in association with obinutuzumab, is a therapeutic option
• In the absence of TP53 mutation and/or del(17p),
  • For patients with no significant comorbidities, the Transparency Committee has deemed that the therapeutic strategy should be adapted according to the patient’s IGVH mutation status.
    • For patients with a mutated IGVH status, the choice between rituximab + fludarabine + cyclophosphamide immunochemotherapy (FCR regimen) and targeted therapy with the IMBRUVICA (ibrutinib) + rituximab association may be discussed.
    • In cases of non-mutated IGVH status (currently recognised as a factor in poor immunochemotherapy response), the IMBRUVICA (ibrutinib) + rituximab association is the first-line treatment.
    • Note that, in France, IMBRUVICA (ibrutinib) monotherapy currently has no reimbursed indication for the first-line treatment of FCR regimen-eligible patients with no TP53 mutation or del(17p).
  • For patients who are older and/or have comorbidities, meaning that they are not eligible for the “full-dose” standard FCR regimen, the options are:
    • Associations of anti-CD20 monoclonal antibody and chemotherapy:
      • GAZYVARO (obinutuzumab) + chlorambucil (G-Clb regimen)
      • MABTHERA (rituximab) + bendamustine (BR)
    • Targeted therapies:
      • VENCLYXTO (venetoclax) + GAZYVARO (obinutuzumab) (G-VEN)
      • IMBRUVICA (ibrutinib) monotherapy.
      • CALQUENCE (acalabrutinib) +/- GAZYVARO (obinutuzumab)

Role of VENCLYXTO (venetoclax) in the therapeutic strategy:

In view of the data available from the CLL14 study demonstrating the superiority of VENCLYXTO (venetoclax) associated with obinutuzumab with respect to the chlorambucil + obinutuzumab (OClb) association in terms of progression-free survival, haematological response rate, and minimal residual disease outcomes, VENCLYXTO (venetoclax) in association with obinutuzumab, is an additional first-line CLL treatment option for patients with no 17p deletion or TP53 mutation and ineligible for fludarabine-based treatment, and for patients with a 17p deletion or a TP53 mutation.

The Committee points out that, although this treatment is preferable over the immunochemotherapy regimens for cases ineligible for ibrutinib, failing comparative data, it is not possible to determine its role with respect to BTK inhibitors.