Available data on anti-BCMA CART-cell therapy has demonstrated efficacy and manageable toxicity in heavily pretreated R/R MM patients. Chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA) represents a new strategy for the treatment of relapsed/refractory MM (R/R).
Idecabtagene Vicleucel (bb2121) |
Ciltacabtagene Autoleucel (JNJ-4528) |
Orvacabtagene Autoleucel (JCAR-H125) |
Idecabtagene Vicleucel (ide-cel, bb2121) |
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Author (year) |
Munshi (2020) |
Berdeja (2019) Alsina (2020) |
Berdeja (2020) Madduri (2020) |
Mailankody (2020) |
Lin (2020) |
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Reference |
[24] |
[31] |
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Study Name |
KarMMa |
CRB-402 |
CARTITUDE-1 |
EVOLVE |
CRB-401 |
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Construct |
The ide-cel CAR is comprised of a murine extracellular single-chain variable fragment (scFv) specific for recognizing BCMA, attached to a human CD8 α hinge and transmembrane domain fused to the T-cell cytoplasmic signaling domains of CD137 4-1BB and CD3-ζ chain, in tandem |
Cells engineered with bb2121 construct are then ex vivo cultured with PI3K inhibitor bb007 |
2 BCMA-targeting single-domain antibodies to boost avidity plus a 4-1BB co-stimulatory domain |
Comprising fully human BCMA-binding domain with low affinity for soluble BCMA, 4-1BB co-stimulatory domain, CD3ζ signaling domain |
The same characteristics asthe KarMMa study |
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Median Age |
61 (range 33–78) |
62 (range, 33–74) |
61 (range, 43–78) |
61 (range, 33–77) |
61 |
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Cell Dose × 106 kg |
150 |
300 |
450 |
150 |
300 |
450 |
0.75 |
300 |
450 |
600 |
50, 150, 450, or 800 × 106 in the dose-escalation phase 150 to 450 × 106 in the dose-expansion phase. |
No. Patients |
4 |
70 |
55 |
12 |
28 |
20 |
97 (29 phase Ib/68 phase II) |
19 |
18 |
7 |
21 patients dose-escalation phase; 41 dose-expansion phase. |
Lymphodepletion |
FLU + CY |
FLU + CY |
FLU + CY |
FLU + CY |
FLU + CY |
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Median Followup |
13.3 |
8.5 |
11.5 |
9.5 |
8.8 |
2.3 |
14.7 |
B-cell maturation antigen (BCMA); Lymhodepletion consisted of Fludarabine (FLU) 30 mg/m2 × 3 days + Cyclophosphamide (CY) 300 mg/m2 × 3 days
Car t Cell Construct |
Idecabtagene Vicleucel (bb2121) |
Ciltacabtagene Autoleucel (JNJ-4528) |
Orvacabtagene Autoleucel (JCAR-H125) |
Idecabtagene Vicleucel (ide-cel, bb2121) |
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---|---|---|---|---|---|---|---|---|---|---|---|
Author (Year) |
Munshi (2020) |
Berdeja (2019) Alsina (2020) |
Berdeja (2020) Madduri (2020) |
Mailankody (2020) |
Lin (2020) |
||||||
Study Name |
KarMMa |
CRB-402 |
CARTITUDE-1 |
EVOLVE |
CRB-401 |
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Reference |
[24] |
[31] |
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Response Rate |
|||||||||||
ORR |
50% |
69% |
82% |
83% |
43% |
73% |
97% |
95% |
89% |
92% |
76(%) |
CR |
25% |
29% |
39% |
18% |
67% |
37% |
42% |
29% |
39(%) |
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Median DoR |
NR |
9.9 |
11.3 |
11.9 |
NR |
NR |
NR |
NR |
10.3(%) |
||
Median PFS |
2.8 |
5.8 |
12.1 |
NR |
NR |
NR |
NR |
9.3 |
NR |
NR |
8.8 (%) |
Evaluable for MRD |
4 |
70 |
54 |
7 |
6 |
4 |
57 |
11 |
11 |
3 |
37 |
MRD- |
50% |
31% |
48% |
100% |
83.3% |
100% |
93% |
72.7% |
90.9% |
100% |
81% |
CRS Event |
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All |
50% |
76% |
96% |
67% |
94.8% |
89% |
76(%) |
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Median Time to First Onset |
7 (2–12) |
2 (1–12) |
1 (1–10) |
3 (1–20) |
7 (1–12) |
2 (1–4) |
Nk |
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Grade 3–4 |
0 |
4% |
6% |
2% |
4% |
3% |
6(%) |
||||
Grade 5 |
0 |
1% |
0 |
2% |
1% |
0 |
0 |
||||
Neurotoxicities |
|||||||||||
All |
0 |
17% |
20% |
22% |
20.6% |
13% |
44% |
||||
Median Time to First Onset |
NA |
3 (1–10) |
2 (1–5) |
7 (3–24) |
8 (3–12) |
4 (1–6) |
Nk |
||||
Grade 3–4 |
0 |
7% |
12% |
4% |
10.3% |
3% |
3% |
||||
Grade 5 |
0 |
0 |
0 |
2% |
0 |
0 |
0 |
B-cell maturation antigen (BCMA); median time to first onset expressed in days (range); median age expressed in years (range); median follow up and progression-free survival (PFS) expressed in months; overall response rate (ORR); complete remission (CR): median duration of response (DoR) expressed in months; not known (Nk).
This entry is adapted from the peer-reviewed paper 10.3390/cancers13112639