The Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA – the EU medicines regulator) has today given a positive recommendation for the extension of the marketing authorisation for the CAR-T treatment ciltacabtagene autoleucel (Carvytki®), also known as cilta-cel, for use in patients who have received at least 1 prior therapy. The full wording of the license extension is as follows:

Carvykti is indicated for 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.

The CHMP decision is based on the results of the Phase III clinical trial data from CARTITUDE-4 which looked at cilta-cel in patients who had 1 – 3 prior lines of therapy and were no longer responding to lenalidomide (i.e. lenalidomide refractory). The trial compared cilta-cel to a physician’s choice of either pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) until disease progression. Patients in the cilta-cel arm also received PVd and DPd bridging therapy, prior to their single infusion of cilta-cel.

Published results of the trial show that one infusion of cilta-cel improved progression free survival (PFS) (i.e., the length of time before their disease progressed) and reduced the risk of disease progression or death by 74% compared to standard treatment.

In terms of side-effects, in the cilta-cel arm 97% of patients had grade 3 – 4 adverse events (severe side-effects). In the standard of care arm 94% of patients had grade 3 – 4 adverse events. These included infections (27% vs 25%) and cytopenias [i.e. reduced blood cell counts] (94% vs 86%). In patients who received cilta-cel, 76% had cytokine release syndrome (CRS – an inflammatory response to CAR-T with symptoms including fever and nausea) (1% grade 3 (severe); no grade 4 – 5) and 5% had immune effector cell associated neurotoxicity syndrome (ICANs – neurotoxicity causing symptoms such as confusion) (all grade 1 – 2).

Cilta-cel is currently approved by the European Commission for myeloma patients who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti‑CD38 antibody and whose disease has worsened since the last treatment. The new CHMP recommendation means that cilta-cel will be licenced for use in earlier stages of myeloma (after at least one prior treatment).

The European Commission now has 60 days in which to consider and adopt the CHMP commission recommendation. Once approved by the European Commission, it means cilta-cel is considered safe and effective for use in patients across Europe.

MPE interviewed Dr. Hermann Einsele, Director of the Department of Internal Medicine II at the Würzburg University Hospital, Germany, at the European Hematology Association annual congress 2023 about the CARTITUDE-4 study. You can watch the video interview here.

For further information on cilta-cel, you can read the MPE ciltacabtagene autoleucel factsheet here.