Blinatumomab (7) – Blincyto®

• Clinical trials
  • The MT103-205 trial investigated paediatric patients aged ≥ 28 days to < 18 years with B-ALL, who had relapsed following ≥ 2 prior lines of treatment or following a prior allogeneic haematopoietic stem cell transplant, or who were refractory to other treatments.
  • Study 20120215 is a multicentre, randomised, controlled, open-label Phase III trial involving paediatric patients with high-risk first relapse of Ph- CD19+ B-ALL, to evaluate the efficacy and safety of blinatumomab as consolidation therapy compared with standard high-risk consolidation therapy.

Paediatric patients aged ≥ 1 month to < 1 year with Philadelphia chromosome-negative, CD19-positive B-cell progenitor ALL, which is refractory or has relapsed following at least two prior lines of treatment, or has relapsed following a prior allogeneic haematopoietic stem cell transplant

• In summary, the additional benefit of blinatumomab is assessed as follows:
• Hint for a non-quantifiable additional benefit, as the scientific evidence does not permit quantification.
• Consequently, the G-BA classifies the extent of the additional benefit of blinatumomab in the treatment of paediatric patients aged ≥ 1 month to < 1 year with Philadelphia chromosome-negative, CD19-positive B-cell progenitor ALL, which is refractory or has relapsed following at least two previous lines of treatment, or has relapsed following a previous allogeneic haematopoietic stem cell transplant, is non-quantifiable.
• There is an additional benefit in accordance with Section 35a(1), sentence 11, first half-sentence, of SGB V, but it is non-quantifiable because the scientific evidence does not permit this.
• The certainty of the findings is assessed as a hint due to the limitations of the available evidence.
• mortality
  • For infants with Philadelphia chromosome-negative, CD19-positive B-cell progenitor ALL, which is refractory or has relapsed after at least two previous lines of treatment, or has relapsed following a previous allogeneic haematopoietic stem cell transplant, no clinical trials are available.
  • The clinical data for the 9 individuals aged < 1 year from the single-arm studies MT103-205 and RIALTO, identified in the EMA’s literature search, were not submitted for the benefit assessment.
• morbidity
  • For infants with Philadelphia chromosome-negative, CD19-positive B-cell progenitor ALL that is refractory or has relapsed following at least two prior lines of treatment, or has relapsed following a prior allogeneic haematopoietic stem cell transplant, there are no clinical trials available.
  • The clinical data for the 9 subjects aged < 1 year from the single-arm studies MT103-205 and RIALTO, identified in the EMA’s literature search, were not submitted for the benefit assessment.
• Health-related quality of life
  • For infants with Philadelphia chromosome-negative, CD19-positive B-cell progenitor ALL that is refractory, has relapsed after at least two prior lines of treatment, or has relapsed following a prior allogeneic haematopoietic stem cell transplant, no clinical trials are available.
  • The clinical data for the 9 individuals aged < 1 year from the single-arm studies MT103-205 and RIALTO, identified in the EMA’s literature search, were not submitted for the benefit assessment.
• Side effects
  • For infants with Philadelphia chromosome-negative, CD19-positive B-cell progenitor ALL that is refractory or has relapsed following at least two prior lines of therapy, or has relapsed following a prior allogeneic haematopoietic stem cell transplant, there are no clinical trials available.
  • The clinical data for the 9 subjects aged < 1 year from the single-arm studies MT103-205 and RIALTO, identified in the EMA’s literature search, were not submitted for the benefit assessment.
• Conclusion
  • For infants with Philadelphia chromosome-negative, CD19-positive B-cell precursor ALL, which is refractory or has relapsed after at least two previous lines of treatment, or has relapsed following a previous allogeneic haematopoietic stem cell transplant, there are no comparative data from clinical trials available to assess the extent of the additional benefit.
  • The pharmaceutical manufacturer bases its evidence for the extent of the additional benefit on an evidence transfer of the results of clinical trials 20120215 and MT103-205, extrapolating findings from older paediatric patients to infants.
  • The evidence transfer from older paediatric patients to infants, as sought by the pharmaceutical manufacturer, is not accepted here, in particular because no comparative data were available for older paediatric patients in the present therapeutic indication from which extrapolations could be made.

Courtesy translation only, please refer to the German original.