Blinatumomab (8) – Blincyto®

• Clinical trials
  • The subject of this benefit assessment procedure was study 20120215, which investigated the efficacy and safety of blinatumomab as consolidation therapy compared with a high-risk consolidation therapy in paediatric patients with high-risk first relapse of Ph- CD19+ B-ALL.

Paediatric patients aged ≥ 1 month to < 1 year with high-risk first relapse of Philadelphia chromosome-negative, CD19-positive B-cell precursor ALL as part of consolidation therapy

• Hint for a non-quantifiable additional benefit, as the scientific evidence does not permit quantification.
• The certainty of the evidence is rated as a hint due to the limitations of the available evidence.
• No clinical data are available for the benefit assessment of blinatumomab in paediatric patients aged ≥ 1 month to < 1 year (infants) with high-risk first relapse of Philadelphia chromosome-negative, CD19-positive B-cell progenitor ALL as part of consolidation therapy.
• In the marketing authorisation dossier, the pharmaceutical manufacturer refers to the patient population aged ≥ 1 year to < 18 years within the same therapeutic indication, which was assessed in the benefit assessment procedure for blinatumomab by resolution of 20 January 2022.
• The marketing authorisation for blinatumomab in infants with high-risk first relapse of Ph-, CD19+ B-cell precursor ALL as part of consolidation therapy is based on a population pharmacokinetic (pop PK) or a mechanistic physiology-based pharmacokinetic (M-PBPK) modelling using data from adult and paediatric patients aged over 1 year with (B)-ALL and non-Hodgkin’s lymphoma (NHL).
• With regard to the comparability of the high-risk group of infants with the high-risk group of paediatric patients aged ≥1 year to <18 years, it can be assumed, based on the statements of clinical experts during the oral hearing, that sufficient comparability exists.
• The experts explained in this regard that a high-risk relapse is defined as a relapse occurring within the first 18 months following diagnosis; consequently, all relapses occurring in infancy (up to a maximum of 12 months) are, by definition, high-risk relapses.
• Relevant clinical data on this patient group are not expected to become available in the future either, due to the small number of patients who can be recruited.
• The comparative study 20120215, on which the transfer of the additional benefit is based, included a patient cohort whose age range is directly adjacent to that of the patient population under consideration here.
• In the corresponding benefit assessment (resolution of 20 January 2022), blinatumomab was shown to have very clear advantages in paediatric patients aged ≥ 1 year or older with high-risk first relapse of Ph-, CD19+ B-cell precursor ALL.
• Overall assessment
  • In its overall assessment, the G-BA considers it appropriate in this case to extrapolate the findings regarding the additional benefit of blinatumomab from the benefit assessment for paediatric patients aged ≥ 1 year to < 18 years to paediatric patients aged ≥ 1 month to < 1 year (infants) with high-risk first relapse of Ph- CD19+ B-ALL to be appropriate in this case.
  • Due to the associated uncertainties and the limitations of the available evidence, the extent of the additional benefit is non-quantifiable.
  • An additional benefit exists in accordance with Section 35a(1), sentence 11, first half-sentence, of SGB V, but is non-quantifiable because the scientific evidence does not permit this.

Courtesy translation only, please refer to the German original.