Table 1 Clinical developmental summary of CAR T-cell therapies for MCL
From: CAR T-Cell therapy for the management of mantle cell lymphoma
Phase | Intervention | Number enrolled | Adverse event | Remarks | Progression-free survival (PFS) | Overall survival (OS) | NCT number |
|---|---|---|---|---|---|---|---|
Approved | Brexucabtagene Autoleucel (KTE-X19) [105] | 74 | Out of 33 patients, 91% develops CRS, 55% grade 2 and 3% patient with grade 3 adverse event | Best response was observed in 12% of total patients 3% of patient die within 1 month of infusion Overall response rate – 83% | PFS- 77% and 51% for post infusion of 6 and 12 month, respectively | OS- 83% and 61% post 6 and 12 months | NCT04162756 |
184 | Common grade 3 adverse event was observed as neutropenia (80%), anemia (49%), thrombocytopenia (49%) | Serious adverse event was observed in 48% patients •••Median follow-up was done at 6.2 months | PFS- 47% (at 2-year interval) | OS- 59% (at 2-year interval) | NCT03575351 | ||
CD19 CART-T (expressing IL-7 and CCL19) [108] | 39 | Grade 3 cytokine and higher grader (> 3) was observed I 12.8% and 10.3%, respectively | Fourth generation Therapy | PFS- 53.8% after 13 months | OS- Greater than 2 years | NCT04833504 | |
3 | Drug: BTK inhibitor + Fludarabine + Cyclophosphamide + CAR-T-CD19 Cells Drug: Fludarabine + Cyclophosphamide + CAR-T-CD19 Cells | 24 | The study is ongoing and hence the data is not available | The study is ongoing and hence the data is not available | The study is ongoing and hence the data is not available | he study is ongoing and hence the data is not available | NCT05020392 |
2 | M19 CAR T-cells | 68 | Not noted yet | Not yet recruiting | PFS will be noted upto 24 weeks post-infusion once the study starts | OS will be noted upto 24 weeks post-infusion once the study starts | NCT05155215 |
Brexucabtagene autoleucel | 90 | N/A | N/A | Not yet received. PFS will be noted upto 7 years post-infusion | Not yet received. OS will be noted upto 7 years post-infusion | NCT04880434 | |
Biological: brexucabtagene autoleucel Drug: Axicabtagene Ciloleucel [109] | 105 | Toxicities were rare, only 3% of patient develops adverse event on the longer duration | Duration of action was noted as 28.2 months | PFS- 25.8 months | OS- 46.6 months | NCT02601313 | |
Anti-CD19/20-CAR vector-transduced T-cells [110] | 100 | Cytokine release cytokine -50% Grade 1 or 2 and grade are 36% and 14%, respectively | One person died in the clinical trial No cases of encephalopathy | PFS- 12 month (64%) | Data not available | NCT03097770 | |
CAR T-Cell (CAR-20/19-T Cells) [111] | 65 | Not reported | Dose of 2.5 × 106 cells/kg (n = 16) | PSI was 866–1109 and polyfunctionality was 40–45% | Data not available | NCT04186520 | |
Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes (CD19-Specific Chimeric Antigen Receptor) [112] | 204 | The study is ongoing and hence the data is not available | The study is ongoing and hence the data is not available | The study is ongoing and hence the data is not available | The study is ongoing and hence the data is not available | NCT01865617 | |
CTX112 (Anti-CD19 CAR-T Cell Therapy) [113] | 120 | Not available | Not available | Not available | Not available | NCT05643742 | |
MB-106 (CD20-targeted CAR T-cell therapy) [114] | 287 | No CRS or ICANS ≥ Grade 3 | FDA Grants Orphan Drug Designation to MB-106 | Not available | An overall response rate (“ORR”) of 96% and complete response (“CR”) rate of 75% observed in a wide range of hematologic malignancies including follicular lymphoma (“FL”), CLL, diffuse large B-cell lymphoma (“DLBCL”) | NCT05360238 | |
JCAR017 (lisocabtagene maraleucel) [115] | 385 | Adverse event of grade 3 was observed on 79% during treatment and 5% post-infusion | CAR T was present in blood for upto 4 years | PFS- 6.8 months (average) (40.6%) | OS- 27.3 month (average) (50.5%) | NCT02631044 | |
1 | Anti-CD19/20-CAR vector-transduced T-cells [110] | 100 | Fatigue, night sweats, hypotension, injection site reaction, leukopenia, and anemia | Duration of action was 94% and 74% for 6 and 12 months | PFS- 76% and 59% for 6 and 12 months, respectively | The study is ongoing and hence the data is not available | NCT03097770 |
ADI-001(CD20 gamma delta CAR-T) [116] | 78 | Adverse event was observed in 78% in grade ½ | 78% overall and complete response rate and sustained durability in patients | PFS data not available | The study is ongoing and hence the data is not available | NCT04735471 |