FDA approves ciltacabtagene autoleucel for the treatment of patients with RRMM

On February 28, 2022, it was announced that the U.S. Food and Drug Administration (FDA) granted the approval of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed chimeric antigen receptor T-cell therapy, for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who have received ≥4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.¹

The approval was based on the results of the CARTITUDE-1 trial (NCT03548207), a phase 1b/II, multicenter, single arm, open label study, which enrolled a total of 97 patients.¹ Of note, 87.6% were triple-class refractory, and those who received previous BCMA-directed therapy were excluded from this trial.² The 2-year follow-up results presented at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition showed²:

• An overall response rate of 98%, with 83% achieving stringent complete response.
• A median duration of response was not estimable (95% CI: 21.8 months–not estimable).
• A 2-year progression-free survival and overall survival of 60.5% and 74%, respectively.
• A total of 92% of patients achieving MRD negativity at 10⁻⁵.

The most common adverse reactions (occurring in ≥20% of patients) were pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections-pathogen unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting.¹

It is important to note that the safety information includes a boxed warning regarding cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS), Parkinsonism and Guillain-Barré syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, and prolonged and/or recurrent cytopenia. Warnings and precautions also include prolonged and recurrent cytopenias, infections, hypogammaglobulinemia, hypersensitivity reactions, secondary malignancies, and effects on ability to drive and use machines.³

Currently, cilta-cel is being evaluated by the European Medicine Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) and in various other clinical trials in the field of myeloma (see Table 1 below).

Table 1. Ongoing/planned clinical trials investigating ciltacabtagene autoleucel for the treatment of patients with multiple myeloma