The European Commission ( EC ) has granted conditional marketing authorisation of Carvykti ( Ciltacabtagene autoleucel; Cilta-cel ) for the treatment of adults with relapsed and refractory multiple myeloma ( RRMM ) who have received at least three prior therapies, including an immunomodulatory agent ( IMiD ), a proteasome inhibitor ( PI ) and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy.
Cilta-cel is a chimeric antigen receptor T-cell ( CAR-T ) therapy featuring two B-cell maturation antigen ( BCMA )-targeting single domain antibodies.
CAR-T therapy is specifically developed for each individual patient, and it is administered as a single infusion.
Conditional marketing authorisation ( CMA ) is the approval of a medicine that addresses unmet medical needs of patients based on less comprehensive data than normally required, where the benefit of immediate availability of the medicine outweighs the risk, and the applicant is able to provide comprehensive clinical data in the future.
The CMA was supported by the pivotal CARTITUDE-1 study, including patients who had received a median of six prior treatment regimens ( range, 3–18 ), and had previously received an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 monoclonal antibody.
Findings presented at the American Society of Clinical Oncology ( ASCO ) 2021 Annual Meeting have shown that at a median duration of 18 months follow-up ( range, 1.5–30.5 ), a one-time treatment with Cilta-cel resulted in deep and durable responses, with 98% ( 95% Confidence Interval [ CI ], 92.7–99.7 ) of patients with relapsed and refractory multiple myeloma responding to therapy ( 98% overall response rate [ ORR ]; n=97 ).
Notably, 80% of patients achieved a stringent complete response ( sCR ), a measure in which a physician is unable to observe any signs or symptoms of disease via imaging or other tests after treatment.
The safety of Cilta-cel was evaluated in 179 adult patients across two open-label clinical trials ( MMY2001 and MMY2003 ).
The most common adverse reactions ( greater than or equal to 20% ) were neutropenia ( 91% ), cytokine release syndrome ( CRS ) ( 88% ), pyrexia ( 88% ), thrombocytopenia ( 73% ), anaemia ( 72% ), leukopenia ( 54% ), lymphopenia ( 45% ), musculoskeletal pain ( 43% ), hypotension ( 41% ), fatigue ( 40% ), transaminase elevation ( 37% ), upper respiratory tract infection ( 32% ), diarrhoea ( 28% ), hypocalcaemia ( 27% ), hypophosphataemia ( 26% ), nausea ( 26% ), headache ( 25% ), cough ( 25% ), tachycardia ( 23% ), chills ( 23% ), encephalopathy ( 22% ), decreased appetite ( 22% ), oedema ( 22% ), and hypokalaemia ( 20% ).
The longer-term efficacy and safety profile of Cilta-cel is being assessed in the ongoing CARTITUDE-1 study. Two-year follow-up results have shown that 98% of patients treated with Cilta-cel for relapsed and refractory multiple myeloma responded to therapy, and the majority of patients has achieved sustained depth of response.
Cilta-cel is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient’s own T-cells with a transgene encoding a chimeric antigen receptor ( CAR ) that identifies and eliminates cells that express BCMA.
BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B-cells and plasma cells.
The Cilta-cel CAR protein features two BCMA-targeting single domain antibodies designed to confer high avidity against human BCMA.
Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.
In Europe, more than 50,900 people were diagnosed with multiple myeloma in 2020, and more than 32,500 patients died. While some patients with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels or kidney failure. ( Xagena )
Source: Janssen Pharmaceutical, 2022