CARVYKTI (ciltacabtagene autoleucel) - Multiple myeloma

The clinical benefit of CARVYKTI (ciltacabtagene autoleucel) is substantial in the MA indication.

Considering:

• evidence in an open-label, randomised phase 3 study of the superiority of CARVYKTI (ciltacabtagene autoleucel) compared to the DPd or PVd regimens (investigator’s choice treatment), in terms of:
  •  progression-free survival (primary endpoint) as assessed by a computerised algorithm validated under the management of a laboratory blinded to the treatment allocated, and defined by IMWG criteria: HR = 0.26 (CI95%: [0.18; 0.38]), p-value < 0.0001 without taking into account progression events occurring in the first 8 weeks, otherwise HR = 0.40 (CI95%: [0.29; 0.55]);
  • complete response or stringent complete response rate as assessed by a computerised algorithm (ranked secondary endpoint): OR = 10.3; CI95%: [6.5; 16.4]), p < 0.0001;
  • overall response rate (ranked secondary endpoint): OR = 3.0; CI95%: [1.8; 5.0]), p < 0.0001;
  • overall minimum residual disease (MRD) negativity rate (ranked secondary endpoint): OR = 8.7; CI95%: [5.4; 13.9]), p < 0.0001;
  • overall survival (ranked secondary endpoint) on the second interim analysis performed on 01/05/2024 with an HR = 0.55; CI95%: [0.39; 0.79]), p = 0.0009 < 0.0108;
  • time to worsening of symptoms according to the MySIm-Q score with 79 deteriorations ob served (30 in the cilta-cel group and 49 in the control group) and an HR = 0.38; CI95%: [0.24; 0.61]), p < 0.0001. The median time to worsening of the score was 23.7 months in the cilta cel group, and 18.86 months in the control group; 

and despite:

• a crossover of progression-free survival curves, with a higher number of progressions in the cilta-cel group during the first 8 weeks before injection of the cells, with no clear explanation, a crossover that is also found on the overall survival curves, thereby suggesting an increase in early mortality pending reinjection, before a potential delayed benefit;
•  a safety profile marked, in particular, by neurotoxicity and a long-term risk of secondary haematological cancer, requiring more data to eliminate uncertainties with respect to the longer term general safety profile of this CAR-T;
• the impossibility of positioning it compared to ABECMA (idecabtagene vicleucel) in patients from their second multiple myeloma relapse, in the absence of robust data.

The Committee deems that CARVYKTI (ciltacabtagene autoleucel) provides a moderate clinical added value (CAV III) compared to the DPd [daratumumab – pomalidomide – dexamethasone] and PVd [pomalidomide – bortezomib – dexamethasone] regimens in the treatment of adult patients with relapsed and refractory multiple myeloma, who have received at least one prior therapy, including an immunomodulatory agent and a proteasome inhibitor, have demonstrated disease progression on the last therapy, and are refractory to lenalidomide.