BLINCYTO (blinatumomab) - Lymphoblastic leukaemia (ALL)

The clinical benefit of BLINCYTO (blinatumomab) 38.5 micrograms powder for concentrate and solution for solution for infusion is substantial as part of consolidation therapy for the treatment of adult patients with Philadelphia chromosome negative CD19 positive B-cell precursor acute lymphoblastic leukaemia (ALL) in first complete remission with negative minimal residual disease (MRD).  

Considering:

• evidence of a superiority of BLINCYTO (blinatumomab) in addition to consolidation chemotherapy, compared to consolidation chemotherapy alone, in adult patients aged 30 to 70 years with newly diagnosed BCR-ABL1 gene fusion-negative B-cell precursor ALL an negative MRD status, in a phase 3, comparative, randomised, open-label study (ECOG-ACRIN E1910 study), in terms of overall survival (OS) with:
  • HR = 0.44 (95% CI: [0.25; 0.76]; p = 0.003),
  • OS medians not reached in either of the two treatment groups,
•  and 5-year OS rates of 82.4% (95% CI [73.7; 88.4]) versus 62.5% (95% CI [52.0; 71.3]);
•  the medical need currently partially met by the available alternatives;
• the safety profile, which is deemed to be acceptable to date; 

and despite:

• the open-label design of the study;
• the exploratory nature of the secondary endpoints, in particular relapse-free survival and the endpoints relative to allogeneic HSCT;
• the methodological limitations concerning collection of safety data: SAEs, AEs leading to treat ment suspension or discontinuation, grade 1-2 AEs, with the times to onset and durations of the AEs not having been collected/presented, limiting interpretation of these data;
• the lack of quality of life data;
• limitations concerning the transposability of the population included in the study to the indication concerned, given the following factors:
  • the chemotherapies used during the consolidation phase of the study (4 chemotherapy cycles) are less intense than the protocols used in routine practice in France (6 to 8 cycles in the GRAALL and Hyper-CVAD protocols), particularly in young adults,
  • the marked difference in the definition of negative MRD status: in the ECOG-ACRIN E1910 study, achievement of negative MRD at D28 is more favourable than the definition currently used in France to define the standard risk patient group (MRD < 10-4 at D72,
  • high percentages (25% and 29.5%) of recourse to transplantation in patients with a negative MRD status that do not reflect routine practice in France (expert opinion). It should be recalled that, to date, no benefit has been demonstrated for the contribution of HSCT in MRD-negative patients. Furthermore, MRD was measured using a different flow cytometry method 
    to that used in France;
• the absence of efficacy and safety data in adult patients aged from 18 to 30 years with Philadelphia chromosome negative CD19 positive B-cell precursor ALL in first complete remission with negative MRD. However, it should be noted that:
  • the pathophysiology of MRD-negative Philadelphia chromosome negative CD19 positive B-cell precursor ALL is comparable in young adults and in adults over the age of 30 (expert opinion), 
  • furthermore, the results of a study conducted in B-cell precursor ALL with positive MRD, in first or second complete remission (MT103-203 study) suggest a comparable efficacy in adults aged 18 to 34 years compared to the other age groups; 

the Committee deems that BLINCYTO (blinatumomab) 38.5 micrograms powder for concentrate and solution for solution for infusion provides a moderate clinical added value (CAV III) as part of consolidation therapy for the treatment of adult patients with Philadelphia chromosome negative CD19 positive B-cell precursor acute lymphoblastic leukaemia (ALL) in first complete remission with negative minimal residual disease (MRD).  

https://www.has-sante.fr/jcms/p_3752475/fr/blincyto-07102025-avis-economique-ceesp-855