Idecabtagen vicleucel (1) – Abecma®

• Clinical trials
  • The ongoing KarMMa trial is an open-label, single-arm Phase II trial enrolling people with multiple myeloma who had received at least three previous treatment regimens, including a proteasome inhibitor (PI), an immunomodulator (IMiD) and a CD38 antibody, and who were refractory to their most recent treatment.
  • The ongoing, supportive CRB-401 trial is a two-part, non-randomised Phase I trial in people with relapsed and refractory multiple myeloma. The trial consists of a dose-escalation phase (Part A) and a dose-expansion phase (Part B).

Adults with relapsed and refractory multiple myeloma who have received at least three prior lines of therapy, including an immunomodulator, a proteasome inhibitor and an anti-CD38 antibody, and who have shown disease progression during their most recent treatment.

• Overall, the extent of the additional benefit is classified as non-quantifiable, as the scientific evidence does not permit quantification.
• As only single-arm data are available and a comparative assessment is not possible, the certainty of the evidence is rated as a hint.
• Overall, this results in a hint of a non-quantifiable additional benefit with regard to the strength of the evidence.
• mortality
  • Overall survival was defined in the KarMMa and CRB-401 studies as the time from the Ide-Cel infusion to death from any cause.
  • The median survival time for the KarMMa study is 23.3 months.
  • Due to the single-arm study design, a comparative assessment of the overall survival results is not possible.
• Morbidity – Progression-free survival
  • Progression-free survival (PFS) was assessed using the International Myeloma Working Group (IMWG) criteria as described by Kumar et al (2016), based on laboratory parameters as well as haematological and imaging procedures.
  • The median PFS in the KarMMa study was 9.1 months and in the CRB-401 study 9.9 months.
  • Due to the single-arm study design, a comparative assessment of the PFS data is not possible.
• Morbidity – Health status (EQ-5D VAS)
  • Health status was assessed only in the KarMMa study using the visual analogue scale (VAS).
  • The response rates are calculated by the pharmaceutical manufacturer in the dossier solely on the basis of those treated with Ide-Cel.
  • The EQ-5D VAS data are therefore considered unusable for the present benefit assessment.
  • Notwithstanding this, a comparative assessment of the EQ-5D VAS data is not possible due to the single-arm study design.
• Morbidity – Symptoms
  • Symptoms were assessed exclusively in the KarMMa study using the symptom scales of the EORTC-QLQ-C30 questionnaire and the myeloma-specific supplementary module EORTC-QLQ-MY20.
  • The analyses of symptoms are based on the PRO analysis set.
  • It is not possible to assess the response rates in relation to all individuals who have undergone leukapheresis and are still alive.
  • Consequently, the analyses of the symptom scales from the EORTC-QLQ-C30 questionnaire and the myeloma-specific supplementary module EORTC-QLQ-MY20 are considered unusable for the present benefit assessment.
  • Notwithstanding this, a comparative evaluation of the data on the EORTC QLQ-C30 and -MY20 is not possible due to the single-arm study design.
• quality of life
  • Health-related quality of life was assessed exclusively in the KarMMa study using the functional scales of the EORTC-QLQ-C30 questionnaire and the myeloma-specific supplementary module EORTC-QLQ-MY20.
  • The analyses of health-related quality of life are based on the PRO analysis set.
  • It is not possible to assess the response rates in relation to all individuals who underwent leukapheresis and are still alive.
  • Consequently, the analyses of the functional scales of the EORTC-QLQ-C30 questionnaire and the myeloma-specific supplementary module EORTC-QLQ-MY20 are considered unusable for the present benefit assessment.
  • Notwithstanding this, a comparative assessment of the data on the EORTC QLQ-C30 and -MY20 is not possible due to the single-arm study design.
• Side effects
  • The collection of endpoints relating to side effects differs depending on the study phase of the KarMMa and CRB-401 trials.
  • SAEs occurred primarily during the treatment phase between the Ide-Cel infusion and the end of follow-up in approximately 70% and 76% of participants, respectively.
  • Severe AEs were observed in approximately 30% and 35% of participants, respectively, during the study phase between leukapheresis and LDC; in approximately 54% and 65 per cent of participants, and in the phase between the Ide-Cel infusion and the end of follow-up in > 97 per cent of participants.
  • With regard to UESI, cytokine release syndrome (CRS) occurred in 84% and 92% of patients, respectively, in the phase following the Ide-Cel infusion.
  • Due to the single-arm study design, a comparative assessment of the data on side effects is not possible.
• Overall assessment
  • This benefit assessment is based on the results of the pivotal Phase II KarMMa trial on mortality, morbidity, health-related quality of life and side effects. In addition, data from the supportive Phase I CRB-401 trial on mortality and side effects are available.
  • Due to the single-arm study design, a comparative assessment of the data on idecabtagen vicleucel is not possible.
  • The indirect comparisons carried out between the efficacy endpoints of the KarMMa trial and those of the NDS-MM-003, PREAMBLE and MM-007 trials are subject to major uncertainty, primarily due to clinically relevant confounders that were not taken into account.
  • Overall, the indirect comparisons presented are not suitable for drawing conclusions about the extent of the additional benefit.
  • On balance, the extent of the additional benefit is classified as non-quantifiable, as the scientific evidence does not permit quantification.

Courtesy translation only, please refer to the German original.