All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit the International Myeloma Foundation or HealthTree for Multiple Myeloma.
Introducing
Now you can personalise
your Multiple Myeloma Hub experience!
Bookmark content to read later
Select your specific areas of interest
View content recommended for you
Find out moreThe Multiple Myeloma Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the Multiple Myeloma Hub cannot guarantee the accuracy of translated content. The Multiple Myeloma Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.
The Multiple Myeloma Hub is an independent medical education platform, sponsored by Bristol Myers Squibb, GSK, Pfizer, Roche and Sanofi. The levels of sponsorship listed are reflective of the amount of funding given. Digital educational resources delivered on the Multiple Myeloma Hub are supported by an educational grant from Janssen Biotech, Inc. View funders.
Bookmark this article
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.
Subscribe to get the best content related to multiple myeloma delivered to your inbox