Idecabtagen vicleucel (3) – Abecma®

• Clinical trials
  • In the KarMMa-3 trial, idecabtagen vicleucel was compared with treatment as clinically indicated, with options including daratumumab + pomalidomide + dexamethasone (DPd), daratumumab + bortezomib + dexamethasone (DVd), ixazomib + lenalidomide + dexamethasone (IRd), carfilzomib + dexamethasone (Kd), or elotuzumab + pomalidomide + dexamethasone (Epd), taking into account the patient’s most recent treatment regimen.

Adults with relapsed and refractory multiple myeloma who have received at least two prior treatments and have shown disease progression during their most recent treatment; prior treatment includes an immunomodulator, a proteasome inhibitor and an anti-CD-38 antibody

• Overall, the G-BA concludes that, for idecabtagen vicleucel in the treatment of relapsed and refractory multiple myeloma in adults who have received at least two prior treatments and have shown disease progression during their most recent treatment, and who have been pre-treated with an immunomodulator, a proteasome inhibitor and an anti-CD-38 antibody, an additional benefit is not proven compared with a patient-specific treatment regimen.
• mortality
  • Overall survival was defined in the KarMMa-3 study as the time from randomisation to death from any cause.
  • No statistically significant difference was observed between the treatment groups for the endpoint of overall survival.
• Morbidity – Progression-free survival
  • Progression-free survival (PFS) was the primary endpoint of the KarMMa-3 study.
  • PFS is defined as the period from randomisation to the time of first disease progression or death from any cause.
  • There was a statistically significant prolongation of PFS in favour of idecabtagen vicleucel compared with the appropriate comparator therapy.
  • In summary, the available data do not indicate that the statistically significant prolongation of progression-free survival observed with idecabtagen vicleucel – defined as disease progression determined by laboratory parameters, imaging and haematological procedures in accordance with the IMWG criteria — is associated with an improvement in morbidity or health-related quality of life.
  • In this assessment, the results for the PFS endpoint are not taken into account.
• Morbidity – Symptoms
  • Symptoms of the disease were assessed in the KarMMa-3 study using the symptom scales of the EORTC-QLQ-C30 questionnaire and the myeloma-specific supplementary module EORTC-QLQ-MY20.
  • Overall, the event-time analyses submitted by the pharmaceutical manufacturer (time to first / confirmed / sustained deterioration / improvement) and the sensitivity analyses mentioned are therefore not suitable for the benefit assessment.
  • The cLDA analyses cannot be used, regardless of the structural problems with the data collection (important treatment phases prior to lymphocyte-depleting chemotherapy are not recorded in the intervention arm), cannot be used simply because the difference in response rates between the study arms at month 6 was greater than 25 per cent.
  • Overall, for the reasons stated, the results on disease symptoms (EORTC-QLQ-C30; EORTC-QLQ-MY20) cannot be meaningfully interpreted and therefore cannot be used for the benefit assessment.
• Morbidity – Health status (EQ-5D VAS)
  • Health status was assessed using the VAS scale in the EQ-5D questionnaire.
  • In line with the above comments on symptoms, the results regarding health status cannot therefore be meaningfully interpreted and cannot be used for the benefit assessment.
• Health-related quality of life
  • Health-related quality of life was assessed using the functional scales of the EORTC-QLQ-C30 questionnaire and the myeloma-specific supplementary module EORTC-QLQ-MY20.
  • In line with the above comments on symptoms, the results on health-related quality of life cannot therefore be meaningfully interpreted and cannot thus be used for the benefit assessment.
• Side effects (AEs), total
  • In the KarMMa-3 trial, an adverse event occurred in 100% of patients in the intervention arm; in the control arm, the figure was 99% of patients.
• Side effects – Serious adverse events (SAE), severe AEs (CTCAE grade ≥ 3)
  • For the endpoint of serious adverse events, no statistically significant difference was observed in the KarMMa-3 study.
  • For the endpoint of severe AEs (CTCAE ≥ 3), a statistically significant difference was observed to the disadvantage of idecabtagen vicleucel.
• Side effects – Discontinuation due to AEs
  • No suitable analyses are available for the endpoint ‘discontinuation due to AEs’.
  • The descriptive data indicate that only a few discontinuations due to AEs occurred in both treatment groups.
• Side effects – Specific side effects
  • For the specific adverse events of severe neurological toxicity, severe infections and secondary malignancies, no statistically significant difference between the treatment groups is evident in the detailed analysis.
• Overall assessment
  • For the endpoint of overall survival, there is no statistically significant difference between the treatment groups.
  • The presented analyses of disease symptoms (assessed using the EORTC QLQ-C30 and EORTC QLQ-MY20) and on health status (assessed using the EQ-5D-VAS) cannot be meaningfully interpreted and therefore cannot be used for the benefit assessment.
  • With regard to health-related quality of life, as assessed using the scales of the EORTC QLQ-C30 (Global Health Status and Functional Scales) and the EORTC QLQ-MY-20 (Functional Scales), no data that can be meaningfully interpreted – and therefore no data suitable for use in the benefit assessment – are available for the same reasons.
  • With regard to side effects, there is a statistically significant disadvantage for idecabtagen vicleucel compared with patient-specific therapy in terms of the endpoint ‘severe AEs’ (CTCAE grade ≥ 3).
  • Taking the results on side effects as a whole, there is a disadvantage for idecabtagen vicleucel compared with patient-specific therapy.

Courtesy translation only, please refer to the German original.