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The Multiple Myeloma Hub previously summarised activities on chimeric antigen receptor (CAR) T cells in China. Jianxiang Wang presented this topic at the 2nd European CAR T-cell Meeting, which has been summarised here. The article provided a summary of some of the investigational new drugs (IND) developed in China at the time.
At the 3rd European CAR T-cell Meeting, held virtually in February 2021, Jianxiang Wang presented information on the progression of CAR-T trials in China, specifically on reducing manufacturing times (FasTCAR) and incorporating a second target (dual CAR). He reported results from the trials evaluating the efficacy of GC022F and GC012F in relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and multiple myeloma (MM), respectively.1
The data cutoff date was November 4, 2020. The median follow-up was 126 days (range, 14−279 days). There was a transduction efficiency of 29.8% (17.0−60.1%) with the optimized manufacturing process and a 100% manufacture success rate.
The median bone marrow (BM) blasts was 42% (range, 0−73%). See further details on baseline characteristics in Table 1.
Table 1. Baseline characteristics*
Characteristic |
n = 11 |
---|---|
Gender (M/F) |
6/5 |
Median age, years (range) |
11 (3−48) |
BM Blasts at enrollment |
|
≥ 60%, n (%) |
2 (18.2) |
30−59%, n (%) |
4 (36.4) |
5−29%, n (%) |
1 (9.1) |
< 5%, n (%) |
4 (36.4) |
Relapsed after allo-HSCT, n |
1 |
Previous CD19 CAR-T, n |
3 |
Both CD19 CAR-T and allo-HSCT, n |
1 |
allo-HSCT, allogeneic hematopoietic stem cell transplant; BM, bone marrow; CAR-T, chimeric antigen receptor T-cell therapy. |
Table 2. Safety*
Adverse event (≥ 25% All Grade), n (%) |
All patients (n = 11) |
|
---|---|---|
All Grades |
Grade ≥ 3 |
|
Leukopenia |
11 (100) |
11 (100) |
Lymphopenia |
10 (91) |
10 (91) |
Thrombocytopenia |
9 (82) |
3 (27) |
Anemia |
9 (82) |
4 (36) |
Neutropenia |
8 (73) |
8 (73) |
Fever |
7 (64) |
1 (9) |
Hypocalcemia |
4 (36) |
0 (0) |
Hypokalemia |
4 (36) |
0 (0) |
Elevated ALT/AST |
3 (27)/3 (27) |
0 (0) |
ALT, alanine aminotransferase; AST, aspartate aminotransferase. |
Figure 1. Dose levels of GC012F*
C, cyclophosphamide; D, day; F, fludarabine; h, hours; QC, quality control.
*Adapted from Wang J. 20211
†Lymphodepletion regime was 30 mg/m2/day fludarabine and 300 mg/m2/day cyclophosphamide for 3 days.
Table 3. Patient baseline characteristics*
Characteristic |
n = 16 |
---|---|
Median age, years (range) |
56 (27−71) |
Male, n (%) |
10 (63) |
Type, n (%) |
|
IgG |
7 (44) |
IgA |
4 (25) |
IgD |
3 (19) |
Light chain |
2 (13) |
Median years since diagnosis (range) |
3 (1−10) |
High-risk profile†, n (%) |
15 (94) |
Double-hit‡, n (%) |
3 (19) |
Extramedullary plasmacytomas ≥ 1, n (%) |
5 (31) |
Median prior regimens of therapy, n (range) |
5 (2−9) |
Median prior lines of therapy, n (range) |
5 (2−7) |
Prior auto-SCT, n (%) |
4 (25) |
Triple exposed§,ǁ, n (%) |
15 (94) |
PI refractory |
15 (94) |
IMiD refractory |
14 (88) |
Anti-CD38 refractory |
4 (25) |
Penta exposedǁ, n (%) |
10 (63) |
Primary refractory, n (%) |
3 (19) |
Refractory to last therapy, n (%) |
12 (75) |
Auto-SCT, autologous hematopoietic stem-cell; IMiD, immunomodulatory drugs; PI, proteasome inhibitor. |
Table 4. Safety*
Adverse event |
All Grades, n (%) |
Grade ≥3, n (%) |
---|---|---|
Hematologic TEAE (≥25% All grades) |
||
Lymphopenia |
13 (81) |
13 (81) |
Neutropenia |
13 (81) |
13 (81) |
Leukopenia |
11 (69) |
11 (69) |
Thrombocytopenia |
11 (69) |
11 (69) |
Anemia |
8 (50) |
7 (44) |
Hypoalbuminemia |
8 (50) |
0 (0) |
Nonhematologic TEAE (≥25% All grades) |
||
LDH increase |
11 (69) |
0 (0) |
AST increase |
7 (44) |
5 (31) |
Diarrhea |
4 (25) |
0 (0) |
Lower respiratory tract infection |
3 (19) |
3 (19) |
AST, aspartate aminotransferase; LDH, lactate dehydrogenase; TEAE, treatment-emergent adverse event. |
The preclinical findings suggest that the FasTCAR platform can successfully manufacture the necessary product in 1 day with younger, less exhausted T cells and improved efficacy than conventional dual CAR-T cells.
Early clinical data for the CD19/CD22 FasT dual CAR T-cell GC022F, shows a favorable safety profile and good efficacy in treating R/R B-ALL patients.
Preliminary clinical data with the BCMA/CD19 FasT dual CAR T-cell GC012F, also showed a favorable safety profile, and promising efficacy in treating relapsed MM refractory compared with the currently available therapies.
Further studies with a larger sample size and longer-term follow-up are needed with both FasT dual CAR T-cell products.
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