Table 2.
Selection of ongoing and completed clinical trials of anti-BCMA CAR T cells for treatment of multiple myeloma
| CAR T cell | Lymphodepletion | CAR T cell dose (cells/kg) | CRS | NT | Comment | Identifier |
| NCI | Flu/Cy | 9×106 | 93% | 6% | Grade 3 or 4 CRS was associated with a high level of bone marrow plasma cells and NT was limited in the setting of severe CRS | NCT02215967 |
| (15/16) | (1/16) | |||||
| UPenn (Novartis) | ±Cy | Cohort 1: | 88% | 32% | The median peak fold-increases of IL-6 and several other cytokines were 1 to 2 orders of magnitude lower than that reported in the NCI BCMA CAR T cell study | NCT02546167 |
| 1×108–5×108 CAR T cells; | (22/25) | (8/25) | ||||
| Cohort 2: | ||||||
| Cy+(1×107–5×107) CAR T cells; | ||||||
| Cohort 3: | ||||||
| Cy+(1×108–5×108) CAR T cells | ||||||
| bb2121 | Flu/Cy | 50×106, 150×106, 450×6, 800×106 | 76% | 42% | CRS occurred at mostly grades 1 and 2 (70%), and NT of grade ≥3 occurred in one patient | NCT02658929 |
| (25/33) | (14/33) | |||||
| bb21217 | Flu/Cy | 150×106 | 67% | 25% | All CRS and NT events were manageable and no deaths occurred on this lowest-dose cohort | NCT03274219 |
| (8/12) | (3/12) | |||||
| LCAR-B38M/ | Cy | Median dose: 0.5×106 | 90% | 2% | CRS occurred at mostly grades 1 and 2 (83%), and NT events of grade 1 were resolved within 1 d | NCT03090659 |
| JNJ-68284528 | (51/57) | (1/57) | ||||
| MCARH171 | Cy or Flu/Cy | 1×106; 150×106, 450×106, 800×106 | 60% | 10% | CRS of grade ≥3 occurred in 20% of patients, and no NT events of grade ≥3 were observed | NCT03070327 |
| (6/10)# | (1/10)# | |||||
| FCARH143 | Flu/Cy | 50×106 | 91% | 9% | No CRS of grade ≥3 was observed | NCT03338972 |
| (10/11) | (1/11) | |||||
| JCARH125 | Flu/Cy | 50×106, 150×106, 450×106 | 80% | 25% | CRS of grade ≥3 occurred in 9% of patients, and NT events of grade ≥3 occurred in 7% of patients | NCT03430011 |
| (35/44) | (11/44) | |||||
| P-BCMA-101* | Flu/Cy | 0.75×106, 2×106, 6×106, 10×106, 15×106 | 10% | 5% | Only two cases of potential CRS were reported (grades 1 and 2) | NCT03288493 |
| (2/21) | (1/21) |
CAR, chimeric antigen receptor; NCI, National Cancer Institute; UPenn, University of Pennsylvania; Flu, fludarabine; Cy, cyclophosphamide; CRS, cytokine release syndrome; NT, neurotoxicity.
#
One patient required early steroids and radiation for impending cord compression and was not evaluable for toxicities;
*
P-BCMA-101 is manufactured using the “piggyback” approach, with a non-viral system for DNA delivery plus a small human fibronectin domain for BCMA. Favorable safety profile, high purity (>95% CAR+) and a T stem cell memory (TSCM) phenotype (gradual and prolonged activity)