Table 1.
Definition of CAR-T late hematotoxicity and severity of cytopenia of concern in different studies.
| Reference | Disease | CAR-T Target | Definition | Patients (n) | Severity of concern graded by CTCAE | Incidence | Risk factors | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Neutropenia | Thrombocytopenia | Anemia | Neutropenia | Thrombocytopenia | Anemia | Baseline | Post infusion | |||||
| Cordeiro t al. (2020) (11) | NHL CLL ALL |
CD19 | Cytopenia requiring transfusion or growth factor support after day 90 post infusion. | 19 | 3–4 | 4 | 4 | 16% | 11% | 11% | NR | NR |
| Fried et al. (2019) (12) | NHL ALL |
CD19 | ANC < 1.5 × 109/L, and PLT < 150 × 109/L, after day 21 post infusion. | 29 | 2 | 1 | NR | 76% | 76% | NR | Prior HSCT | CRS SDF-1 |
| ANC < 0.5 × 109/L, PLT < 50 × 109/L and anemia requiring transfusing were classified as severe. | 4 | 3–4 | 4 | 34% | 21% | 17% | ||||||
| Brudno et al. (2022) (13) | NHL MM |
CD19 BCMA |
ANC < 1 × 109/L, PLT < 50 × 109/L, and Hb < 80 g/L, for recurrence or prolonging cytopenia after day 30 post-infusion. | 35a | 3–4 | 3–4 | 3–4 | 37% | 11% | 6% | Baseline anemia and neutropenia | CAR T-cell persistence in BM aspirate |
| 13b | 15% | 23% | 15% | |||||||||
| Wang et al. (2021) (14) | ALL | CD19 CD19/CD22 |
ANC < 0.5 × 109/L, Hb < 60 g/L, PLT < 20 × 109/L, on day 28 post infusion. | 76 | 4 | 4 | 4 | 25%c | Severe baseline cytopenia, bone marrow tumor burden, LDH. | CRS, CRP, ferritin, D-dimer, IFN-γ, IL-10, usage of tocilizumab/steroids | ||
| Rejeski et al. (2022) (15) | B-cell lymphoma | CD19 | ANC < 1 × 109/L after day 21 post infusion. | 235 | 3–4 | NR | NR | 64% | NR | NR | Baseline cytopenia, CRP, ferritin | — |
| Nagle et al. (2021) (16) | DLBCL | CD19 | ANC < 1 × 109/L, and PLT < 50 × 109/L, after day 30 post infusion. | 31 | 3–4 | 3–4 | NR | 58% | 48% | NR | — | CRS, tocilizumab/steroids, peak ferritin, peak CRP |
| Strati et al. (2021) (17) | Large B-cell lymphoma | CD19 | Grade 3–4 cytopenia after day 30 post infusion. | 31 | 3–4 | 3–4 | 3–4 | 29% | 42% | 16% | ECOG = 1, >3 prior therapies, low ALC. | — |
a Thirty-five patients were evaluable for recurrent cytopenia.
b Thirteen patients were evaluable for prolonging cytopenia.
c Lineage-specific incidence not reported.
Time point selected by different studies to define a late event is underlined. NHL, non-Hodgkin lymphoma; CLL, chronic lymphocytic leukemia; ALL, acute lymphocytic leukemia; MM, multiple myeloma; DLBCL, diffuse large B-cell lymphoma; ANC, absolute neutrophil count; PLT, platelet count; Hb, hemoglobin concentration; NR, not reported; SDF-1, stromal cell derived factor-1; ECOG, Eastern Cooperation Oncology Group. - means not reported.