Ciltacabtagen autoleucel (1) – Carvykti®

• Clinical trials
  • The single-arm, open-label Phase Ib/II trial CARTITUDE-1 was conducted to investigate the efficacy and safety of Ciltacabtagen autoleucel in people with relapsed or refractory multiple myeloma who had previously received at least three lines of treatment, including an immunomodulator, a proteasome inhibitor and an anti-CD-38 antibody.
  • The LocoMMotion study is a prospective, non-interventional study which was used by the pharmaceutical manufacturer to conduct an indirect comparison of Ciltacabtagen autoleucel with standard therapy in everyday healthcare situations.
  • The ongoing CARTITUDE-4 study is an open-label, randomised trial comparing Ciltacabtagen autoleucel with PVd or DPd in patients with multiple myeloma who have previously received 1–3 lines of treatment, including an immunomodulator and a proteasome inhibitor.

Adults with relapsed and refractory multiple myeloma who have previously received at least three lines of treatment, including an immunomodulator, a proteasome inhibitor and an anti-CD38 antibody, and who showed disease progression during their last line of treatment

• Hint for a non-quantifiable additional benefit, as the scientific data do 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.
• mortality
  • The endpoint of overall survival was defined in the CARTITUDE-1 study as the time from infusion of Ciltacabtagen autoleucel to the time of the patient’s death.
  • At the time of the data cut-off submitted for the benefit assessment (follow-up period: 28.6 months), a total of 39 individuals (31.5 %) had died. Overall survival at month 24 was 73.9 %.
  • Due to the single-arm study design, a comparative assessment of the overall survival data is not possible.
• Morbidity – Progression-free survival (PFS)
  • In the CARTITUDE-1 study, PFS is defined as the time from infusion of Ciltacabtagen autoleucel to the first documented disease progression according to the criteria of the International Myeloma Working Group (IMWG), based on laboratory parameters as well as haematological and imaging procedures, or death from any cause, whichever occurs first.
  • The median PFS in the CARTITUDE-1 study was 27.4 months.
  • Due to the single-arm study design, a comparative assessment of the PFS data is not possible.
• Morbidity – Overall response rate
  • The overall response rate is the primary endpoint in the CARTITUDE-1 study and is defined as the achievement of a partial response or better, as assessed by an independent review committee using the IMWG criteria.
  • In the CARTITUDE-1 study, the overall response rate was 83.1% in the ITT population.
  • Due to the single-arm study design, a comparative assessment of the data on the overall response rate is not possible.
• Quality of life – EQ-5D-VAS
  • General health status was assessed for patients in Phase II of the CARTITUDE-1 study (PRO population) using the European Quality of Life – 5 Dimensions (EQ-5D-VAS) visual analogue scale.
  • The response rate for the EQ-5D-VAS was already less than 70% by day 100, meaning that the presented responder analyses are not considered suitable for benefit assessment.
• Quality of life – symptom scales of the EORTC-QLQ-C30
  • The assessment of the symptoms fatigue, nausea and vomiting, pain, dyspnoea, insomnia, loss of appetite, constipation and diarrhoea was carried out using the symptom scales of the EORTC-QLQ-C30 in patients in the PRO population of the CARTITUDE-1 study.
  • No data are available for the period between screening and infusion. Consequently, the length of the time interval between the initial assessment (screening) and Day 7 (Day 7 after infusion) is unclear.
• Quality of life – EORTC QLQ-C30 quality of life scales
  • Quality of life was assessed using the EORTC-QLQ-C30 in patients in the PRO population of the CARTITUDE-1 study.
  • No data are available for the period between screening and infusion. Consequently, the length of the interval between the initial assessment (screening) and Day 7 (Day 7 after infusion) is unclear.
  • The response rate for the EORTC QLQ-C30 was already less than 70% by day 100, meaning that the presented responder analyses are not considered suitable for benefit assessment.
• Quality of life – individual items of the EORTC QLQ-MY20
  • Quality of life was assessed in the PRO population of the CARTITUDE-1 study using four individual items from two scales of the QLQ-MY20. The individual items ‘Restlessness and agitation’ from the ‘Treatment side effects’ symptom scale, as well as ‘Thoughts about the illness’, ‘Worry about dying’ and ‘Worry about future health status’ from the ‘Future prospects’ scale were assessed.
  • Based on the documentation provided, it is not clear to what extent the analysis of individual items has been validated, or whether the individual items have only been validated within the context of the questionnaire as a whole.
  • Notwithstanding this, due to the single-arm study design, a comparative assessment of the data against the EORTC QLQ-C30 and -MY20 is not possible.
• Side effects
  • In the CARTITUDE-1 study, at least one adverse event (AE) occurred in 99.2% of patients in the ITT population.
  • Serious AEs occurred in 95.2% of patients, and severe adverse events in 62.9%. The most common adverse events were disorders of the blood and lymphatic system (93.5%), in particular neutropenia (87.1%) and anaemia (70.2%).
  • A comparative assessment of the side effects is not possible due to the single-arm study design.
• Overall view
  • Data for the benefit assessment are available from the single-arm, multicentre Phase Ib/II CARTITUDE-1 trial, which formed the basis for marketing authorisation.
  • With regard to the submitted analyses of the indirect comparison (weighted analyses, PS matching), there are major uncertainties regarding the comparability of the study populations, particularly in terms of balance and high case loss rates. The indirect comparison presented is assessed, on the whole, as failing to provide a data basis that is sufficiently robust to enable reliable conclusions to be drawn regarding the quantification of the additional benefit.
  • The pooled analysis of the CARTITUDE-1, CARTITUDE-4 and LocoMMotion studies is not considered suitable for benefit assessment due to its heterogeneity.
  • The data on the patient population of the CARTITUDE-4 study are not used as the basis for this assessment, but are presented for supplementary information.
  • For the CARTITUDE-1 study, the pharmaceutical manufacturer has submitted data on mortality, morbidity, quality of life and side effects. However, due to the single-arm study design, these data do not allow for a comparative assessment.
  • Overall, 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.