Table 2.
Major lymphodepleting regimens for CAR T-cell therapy and their dosages, advantages, and disadvantages.
| Regimen | Dosage | Advantage | Disadvantage | Refer. |
|---|---|---|---|---|
| Cy | 300 mg/m2 every 12 hours for 3 days | It effectively prolongs the persistence of infused cells and increases the effectiveness of treatment | It could cause adverse effects, ranging from mild to severe symptoms | 117 |
| Bendamustine | 90 mg/m2/day for 2 days | It is an effective lymphodepletion regimen before tisa-cel in R/R lymphoma. It also reduces hematological toxicities and infectious complications compared with Flu/Cy. Lower CRS and neurotoxicity than Flu/Cy. It shows higher neutrophil, hemoglobin, and platelet counts. | It may result in side effects such as fevers, chills, itching, skin rash, nausea, vomiting, fatigue, and more serious side effects infertility and liver injury. | 116 |
| Flu | 25 mg/m2/day for 3-5days | Flu improved CAR–T-cell persistence and PFS compared to Cy alone | No cell persistence in the second round of CAR T-cell treatment, myelosuppression, risk of infection, and neurotoxicity | 115 |
| Bendamustine/Flu | Bendamustine 70 mg/m2/day + Flu 30 mg/m2/day for 3 days | Provide longer persistence of CAR T-cells than Cy/Flu. It markedly increases the level of IL-15 and IL-17 than bendamustine alone. It enhances PFS compared with bendamustine alone or Cy/Flu. Good efficacy and safety profile | It may be associated with CRS | 118 |
| Cy/Flu | Cy 500 mg/m2/day + Flu 30 mg/m2/day for 2–5 days | Increase cell expansion and longer persistence both in CD4 and CD8 cells. It also improves clinical outcomes | This leads to more profound lymphopenia, higher rates of hematological toxicities | 115,116 |
| I-131 apamistamab | 75 mCi | It is a new CD45-targeting antibody radiation-conjugate given as a single-dose outpatient administration; It is a specific, safer, and more effective alternative; less toxic than chemotherapy-based lymphodepletion; prevents CRS | Radiation associated risks | 119,120 |
Abbreviations: CRS, cytokine release syndrome; Cy, Cyclophosphamide; Flu, Fludarabine; PFS, progression-free survival.