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B. Bruno et al.
Ide-cel (bb2121)
The first-in-man study with ide-cel (CRB-401) evaluated escalating doses of CAR-T (50x106, 150x106, 450x106, or 800x106 in the dose-escalation phase, and 150x106-450x106 in the expansion phase) in extensively pretreated MM (median of six prior therapy lines; 69% triple-class refrac- tory).51 Sixty-two patients were enrolled. At least PR was achieved by 76% of patients including complete response (CR) in 39%. All 15 patients with ≥CR who had an assess- ment for minimal residual disease (MRD) were MRD-neg- ative at the level of 10-5. Baseline BCMA expression or sBMCA levels did not affect response. There was a trend towards lower response in patients who received
Table 2. Ide-cel and Cilta-cel: CAR-T and clinical characteristics
Ide-cel (bb2121) / KarMMa (phase II)
Cilta-cel (JNJ-4528) / CARTITUDE-1 (phase IB/ II)
scFv (murine)
CD3ζ/4-1BB
Lentiviral
Bb21217 uses the same CAR construct as used for ide-cel. During ex vivo culture a PI3K inhibitor is added to enrich for CAR-T with memory-like phenotype
Flu/Cy
150-450x106
128 (140 patients underwent leukapheresis)
Bispecific variable fragments of llama heavy-chain antibodies; two distinct BCMA epitopes are targeted
≤150x106 CAR-T, in those with less in vivo CAR-T expan- sion, and in those with high-risk cytogenetic abnormali- ties. Median progression free survival (PFS) was 8.8 months for all patients, and 9.0 months for those who received 450x106 CAR-T. Median overall survival (OS) was 34.2 months. Based on these promising results of the phase I trial, a second trial (KarMMa, phase II study) was initiated to evaluate the value of ide-cel in larger numbers of patients who were previously exposed to immunomod- ulatory drugs (IMiD), a proteasome inhibitor, and a CD38 antibody.50 In this study 140 patients were enrolled with a manufacturing success of 99%; 128 of 140 (91%) received CAR-T, whereby 88% received bridging therapy prior to
Antigen-binding domain
Signaling domains Vector
Other features
Lymphodepletion CAR-T dose Number of patients
Bridging therapy (%)
Number of prior therapies (median)
Triple-class refractory (%)
High-risk cytogenetics (del(17p), t(4;14), or t(14;16) (%)
CD3ζ/4-1BB
Lentiviral
Bi-epitope BCMA binding confers high avidity binding
88 6 84
Flu/Cy
Median dose: 0.71x106/kg
Data presented for first 97 (113 patients were enrolled/apheresed
65
6
88
35 24 13
97%
67%
Median PFS: Not reached; 12-month PFS rate: 77%
95 4 7
4
21 (ICANS: 17%; other neurotoxicity*: 12%) 10 (ICANS: 2%; other neurotoxicity: 9%)
ICANS: 8 days; other neurotoxicities*: 27 days
ICANS: 4 days; other neurotoxicities: 75 days 13
42
Extramedullary disease (%) ≥PR
≥CR
Median PFS
39
150-450x106: 73% 150x106 : 50% 300x106 : 69% 450x106 : 82%
150-450x106: 33% 150x106 : 25% 300x106 : 29% 450x106 : 39%
150-450x106: 8.8 months 150x106 : 2.8 months 300x106 : 5.8 months 450x106 : 12.1 months
84 5 1
5 18 3
2
3 11 59
CRS (all grades) (%)
CRS (grade ≥3) (%)
Median time to CRS onset
(any grade) (days)
Median duration of CRS (any grade) (days)
Neurotoxicity (all grades) (%)
Neurotoxicity (grade ≥3) (%)
Median time to neurotoxicity onset
(any grade) (days)
Median duration of neurotoxicity (any grade) (days)
Time to peak CAR-T expansion (days)
CAR-T persistence 6 months, %
*Other neurotoxicities are defined as neurotoxicities occurring after resolution of cytokine release syndrome (CRS) and/or immune effector cell-associated neurotoxicity syndrome (ICANS). PR: partial response; CR: complete response; PFS: progression free survival.
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haematologica | 2021; 106(8)