European Commission approves cilta-cel for the treatment of RRMM after ≥1 prior LOT

On April 22, 2024, the European Commission granted approval to ciltacabtagene autoleucel (cilta-cel) for the treatment of relapsed/refractory multiple myeloma (RRMM) after one or more prior therapies, including an immunomodulatory agent (IMiD) or proteasome inhibitor (PI), who are lenalidomide-refractory with disease progression on the last therapy.¹

The approval of this new indication for cilta-cel is based on data from the phase III CARTITUDE-4 trial (NCT04181827) in which patients with RRMM and 1–3 prior lines of therapy were randomized to  receive either cilta-cel or a standard of care (SOC) regimen, consisting of daratumumab, pomalidomide, and dexamethasone (DPd) or pomalidomide, bortezomib and dexamethasone (PVd).¹

CARTITUDE-4 pivotal data

• A total of 419 patients were randomized to the cilta-cel (n = 208) or SoC arm (n = 211)
• The overall response rate (ORR) was significantly higher in the cilta-cel arm compared with SoC (Figure 1).²
• Treatment with cilta-cel resulted in a significantly decreased risk of disease progression or death versus the SoC arm at a hazard ratio of 0.26 (95% confidence interval [CI], 0.2–0.4).
• Median progression-free survival was not reached in the cilta-cel arm vs 11.8 months in the SoC arm.¹
• The 12-month progression-free survival rate was 76% in the cilta-cel arm versus 49% in the SoC arm.¹
• The most common adverse events were hematologic, with neutropenia being most frequent Grade 3/4 adverse event in both cohorts (Table 1).¹

Cilta-cel, ciltacabtagene autoleucel; CR, complete response; ORR, overall response rate; PR, partial response; sCR, stringent complete response; SoC, standard of care; VGPR, very good partial response.
*Data from European Medicines Agency.²

Table 1. Adverse events of interest*

AE, adverse event; cilta-cel, ciltacabtagene autoleucel; CRS, cytokine release syndrome; SoC, standard of care. *Data from San-Miguel, et al.3
Adverse events, %	Cilta-cel (n = 208)	SoC (n = 208)
Grade 3/4 neutropenia	90	82
Grade 3/4 thrombocytopenia	41	19
Grade 3/4 anemia	36	14
Serious AEs	44	39
Infection	62	71
CRS	76	-