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MABTHERA - LDGCB / LB / LA-B / LB-like pédiatriques (rituximab)

Opinions on drugs - Posted on Jan 08 2021

Reason for request

New indication

Key points

Favourable opinion for reimbursement of MABTHERA (rituximab) in combination with chemotherapy for the treatment of paediatric patients (aged ≥ 6 months to < 18 years old) with previously untreated advanced stage CD20 positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL)/Burkitt leukaemia (mature B-cell acute leukaemia) (BAL) or Burkitt-like lymphoma (BLL).

What therapeutic improvement?

Therapeutic improvement compared to chemotherapy alone.

Role in the care pathway?

The standard first-line treatment for previously untreated paediatric advanced stage mature B-cell NHL consists of the combination of several chemotherapies.

The prognosis for children and adolescents with NHL has significantly improved in recent decades thanks to the use of short, intensive cycles of systemic and intrathecal chemotherapies.

In France, the 5-year overall survival rate in children under the age of 15 years is estimated to be 88.3% (CI95%: 85.1-90.8) in NHL (with the exception of Burkitt lymphoma) and 92.6% (CI95%: 89.7-94.7) in Burkitt lymphoma according to the French Regional Health Observatory.

However, prognostic factors such as extranodal involvement, in particular of the central nervous system (CNS) and bone marrow, as well as elevated LDH levels, enable the identification of a category of children with a less favourable prognosis (70 to 80% survival). In the event of early relapse, salvage therapies are less effective, with a survival of around 30%.

There is no recent consensus in France relative to the management of mature B-cell NHL in paediatrics. Treatment involves chemotherapies, including, in particular, corticosteroids, anthracyclines, cyclophosphamide, vinca-alkaloids, etoposide, cytarabine, methotrexate administered in combinations, by successive blocks, and respecting a “dose-intensity” principle.

In the latest American NCCN guidelines updated in 2020, the therapeutic management of paediatric patients with aggressive mature B-cell lymphoma involves several polychemotherapy cycle phases (prephase, induction and consolidation) and combines rituximab with this sequential polychemotherapy (R-COPADM, R-CYM, R-CYVE).

Role of the medicinal product in the care pathway

MABTHERA (rituximab) is a first-line treatment in combination with chemotherapy for the treatment of paediatric patients (aged ≥ 6 months to < 18 years old) with previously untreated advanced stage CD20 positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL)/Burkitt leukaemia (mature B-cell acute leukaemia) (BAL) or Burkitt-like lymphoma (BLL).


Clinical Benefit
Substantial

The Committee deems that the clinical benefit of MABTHERA (rituximab) in combination with chemotherapy is substantial in the treatment of paediatric patients (aged ≥ 6 months to < 18 years old) with previously untreated advanced stage CD20 positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL)/Burkitt leukaemia (mature B-cell acute leukaemia) (BAL) or Burkitt-like lymphoma (BLL).

Clinical Added Value
minor

Considering:

  • demonstration of the major contribution of rituximab in adults, particularly in aggressive CD20 positive diffuse large B-cell non-Hodgkin lymphoma, in combination with chemotherapy
  • the role of the rituximab chemotherapy combination in non-Hodgkin lymphomas in both adults and children, established for almost two decades;
  • the known safety profile of MABTHERA (rituximab), comparable to that in adults;
  • the results of the Inter-B-NHL Ritux 2010 study, which, in terms of event-free survival in the interim analysis, suggest an HR=0.33 (CI90% [0.16-0.69]); p=NS for the rituximab in combination with chemotherapy group compared to the chemotherapy group alone, and an HR=0.32 (CI90% [0.17-0.58]) in the “main” analysis, with a two-sided alpha risk threshold of 10%;

despite:

  • numerous methodological limitations limiting the interpretability of the results of the multicentre academic study (Inter-B-NHL Ritux 2010), including the choice of the two-sided alpha risk threshold of 10% and the premature interruption of randomisation (at the first interim analysis), thereby compromising interpretation of the results of this study;
  • an increased toxicity in the MABTHERA group in combination with chemotherapy, particularly infectious toxicity;

the Transparency Committee considers that MABTHERA (rituximab) provides a minor clinical added value (CAV IV) compared to chemotherapy alone in children and adolescents (aged ≥ 6 months to < 18 years old) with previously untreated advanced stage CD20 positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL)/Burkitt leukaemia (mature B-cell acute leukaemia) (BAL) or Burkitt-like lymphoma (BLL).

 

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