The European Commission ( EC ) has granted Conditional Marketing Authorization for Abecma ( Idecabtagene vicleucel; Ide-cel ), a first-in-class B-cell maturation antigen ( BCMA )-directed chimeric antigen receptor ( CAR ) T cell immunotherapy, for the treatment of adult patients with relapsed and refractory multiple myeloma, who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.
Abecma is the first and only CAR T cell therapy approved that is directed to recognize and bind to BCMA, a protein that is nearly universally expressed on cancer cells in multiple myeloma, leading to the death of BCMA-expressing cells.
Abecma is delivered via a single infusion with a target dose of 420 x 10(6) CAR-positive viable T cells within a range of 260 to 500 x 10(6) CAR-positive viable T cells.
The efficacy of Abecma is based on results from the pivotal KarMMa study in which 128 patients with relapsed and refractory multiple myeloma who had received at least three prior therapies including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody and were refractory to the last treatment regimen were treated with Abecma.
In the study, the overall response rate ( ORR ) was 73% ( 95% CI: 66-81 ), and 33% of patients achieved a complete response ( CR; 95% CI: 25-41 ).
Onset of response was rapid with a median time to response of one month.
In addition, responses were durable, with a median duration of response of 10.6 months ( 95% CI: 8.0 – 11.4 ), and 23 months ( 95% CI: 11.4 – 23.3 ) for those who achieved a complete response ( CR ).
In a pooled safety analysis of 184 patients treated with Abecma in the KarMMa and CRB-401 studies, cytokine release syndrome ( CRS ) occurred in 81% of patients, with grade 3 or more CRS, using the Lee grading system, occurring in 5.4% of patients.
There was one case of fatal ( grade 5 ) CRS reported.
The median time to onset of CRS was one day ( range: 1-17 days ) and the median duration of CRS was five days ( range: 1-63 days ).
Any grade neurotoxicity of the 128 patients receiving Abecma in the KarMMa study occurred in 18% of patients, including grade 3 events in 3.1% of patients, with no grade 4 or 5 events occurring.
The median time to onset of neurotoxicity was two days ( range: 1-10 days ) and the median duration was three days ( range: 1-26 days ).
The most common ( more than 20% ) adverse reactions in the pooled safety analysis included neutropenia, cytokine release syndrome, anaemia, thrombocytopenia, infections - pathogen unspecified, leucopenia, fatigue, diarrhoea, hypokalaemia, hypophosphataemia, nausea, lymphopenia, pyrexia, cough, hypocalcaemia, infections - viral, headache, hypomagnesaemia, upper respiratory tract infection, arthralgia, and oedema peripheral.
The most common grade 3 or 4 adverse reactions were neutropenia ( 88.6% ), anaemia ( 58.2% ), thrombocytopenia ( 53.5% ), leucopenia ( 45.1% ), lymphopenia ( 30.4% ), infections - pathogen unspecified ( 17.9% ), hypophosphataemia ( 17.4% ), febrile neutropenia ( 14.7% ), hypocalcaemia ( 7.1% ), infections - viral ( 7.1% ), pneumonia ( 6.0% ), cytokine release syndrome ( 5.4% ), hypertension ( 5.4% ) and hyponatraemia ( 5.4% ).
In Europe, nearly 50,000 people are diagnosed with multiple myeloma each year. Despite advances in treatment, multiple myeloma remains an incurable disease, and many patients suffer through periods of remission and relapse.
Patients with relapsed and refractory multiple myeloma who have been exposed to all three major drug classes often have poor clinical outcomes and few remaining treatment options.( Xagena )
Source: Bristol Myers Squibb, 2021