Table 1 |.
Reported causes of death after CAR-T-cell therapies (excluding progressive disease)
| Study | Malignancy | Patient age (years) | CAR-T-cell product* (designation or name) | CAR-T-cell dose (per kg) | Day of death after CAR-T-cell infusion | Cause of death‡ |
|---|---|---|---|---|---|---|
| Morgan et al. (2010)88 | Metastatic colon cancer | 39 | HER2-28-137-ζ | 1×1010 total cells | 5 | ARDS |
| Brentjens et al. (2010)94 | CLL | 69 | CD19–28-ζ (19–28z) | 1.2–3.0×107 | 2 | CRS |
| Frey et al. (2014)44 | B-ALL | >18 | CD19–137-ζ (tisagenlecleucel, previously known as CTL019) | 6.5×106 | 5 | CRS(+Influenza B) |
| 6.7×106 | 15 | CRS (+ Pseudomonas sepsis, pneumonia) | ||||
| 8.4×106 | 15 | CRS (+ Stenotrophomonas sepsis, pneumonia) | ||||
| Kochenderfer et al. (2015)11 | PMBCL | 30 | CD19–28-ζ | 2.5×106 | 16 | Unknown (possibly cardiac arrhythmia) |
| Chong et al. (2016)95 | FL | >18 | CD19–137-ζ (tisagenlecleucel) | NA | NA | Encephalitis |
| Neelapu et al. (2016)24(ZUMA-1) | DLBCL | >18 | CD19–28-ζ (axicabtagene ciloleucel; axi-cel, also known as KTE-C19) | 2×106 | NA | HLH |
| Locke et al. (2016)96(ZUMA-l) | NHL | >18 | CD19–28-ζ (axi-cel) | 2×106 | NA | Cardiac arrest |
| Turtle et al. (2016)17 | B-ALL | 48 | CD19–137-ζ | 11.6×106CD4++8.4×106CD8+ | 3 | CRS |
| 52 | CD19–137-ζ | 1×106CD4++1×106CD8+ | 122 | Neurotoxicity | ||
| Turtle et al. (2016)18 | NHL | >18 | CD19–137-ζ | 10×106CD4++10×106CD8+ | 30 | CRS (+CI bleed) |
| 10×106CD4++10×106CD8+ | 13 | Neurotoxicity (+ CNS bleed) | ||||
| ROCKET (2017)64,69 | B-ALL | NA | CD19–28-ζ (JCAR015) | NA | NA | Cerebral oedema (5 cases) |
| ZUMA-1(2017)70 | NHL | >18 | CD19–28-ζ (axi-cel) | NA | NA | Cerebral oedema |
| Turtle et al. (2017)19 | CLL | 62 | CD19–137-ζ | 1×106CD4++1×106CD8+ | 11 | Cerebral oedema |
ζ, T-cell receptor CD3ζ chain; 137, CD137 (4–1BB); 28, CD28; ARDS, acute respiratory distress syndrome; B-ALL, B-cell acute lymphoblastic leukaemia; CAR, chimeric antigen receptor; CLL, chronic lymphocytic leukaemia; CNS, central nervous system; CRS, cytokine-release syndrome; DLBCL, diffuse large-B-cell lymphoma; FL, follicular lymphoma; GI, gastrointestinal; HLH, haemophagocytic lymphohistiocytosis; NA, not available; NHL, non-Hodgkin lymphoma; PMBCL, primary mediastinal B-cell lymphoma.
*
In the format: target antigen/co-stimulatory domain/T-cell-receptor activation domain.
‡
Single case, unless otherwise noted.