Dose fractionation of CAR-T cells. A systematic review of clinical outcomes
Abstract CAR-T cells are widely recognized for their potential to successfully treat hematologic cancers and provide durable response. However, severe adverse events such as cytokine release syndrome (CRS) and neurotoxicity are concerning. Our goal is to assess CAR-T cell clinical trial publications...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-022-02540-w |
| _version_ | 1828063433266823168 |
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| author | Matthew Frigault Anand Rotte Ayub Ansari Bradford Gliner Christopher Heery Bijal Shah |
| author_facet | Matthew Frigault Anand Rotte Ayub Ansari Bradford Gliner Christopher Heery Bijal Shah |
| author_sort | Matthew Frigault |
| collection | DOAJ |
| description | Abstract CAR-T cells are widely recognized for their potential to successfully treat hematologic cancers and provide durable response. However, severe adverse events such as cytokine release syndrome (CRS) and neurotoxicity are concerning. Our goal is to assess CAR-T cell clinical trial publications to address the question of whether administration of CAR-T cells as dose fractions reduces toxicity without adversely affecting efficacy. Systematic literature review of studies published between January 2010 and May 2022 was performed on PubMed and Embase to search clinical studies that evaluated CAR-T cells for hematologic cancers. Studies published in English were considered. Studies in children (age < 18), solid tumors, bispecific CAR-T cells, and CAR-T cell cocktails were excluded. Data was extracted from the studies that met inclusion and exclusion criteria. Review identified a total of 18 studies that used dose fractionation. Six studies used 2-day dosing schemes and 12 studies used 3-day schemes to administer CAR-T cells. Three studies had both single dose and fractionated dose cohorts. Lower incidence of Grade ≥ 3 CRS and neurotoxicity was seen in fractionated dose cohorts in 2 studies, whereas 1 study reported no difference between single and fractionated dose cohorts. Dose fractionation was mainly recommended for high tumor burden patients. Efficacy of CAR-T cells in fractionated dose was comparable to single dose regimen within the same or historical trial of the same agent in all the studies. The findings suggest that administering dose fractions of CAR-T cells over 2–3 days instead of single dose infusion may mitigate the toxicity of CAR-T cell therapy including CRS and neurotoxicity, especially in patients with high tumor burden. However, controlled studies are likely needed to confirm the benefits of dose fractionation. |
| first_indexed | 2024-04-10T22:45:15Z |
| format | Article |
| id | doaj.art-bc11f9c5d417482aa163c574c355e2e3 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-04-10T22:45:15Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-bc11f9c5d417482aa163c574c355e2e32023-01-15T12:24:27ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662023-01-0142111010.1186/s13046-022-02540-wDose fractionation of CAR-T cells. A systematic review of clinical outcomesMatthew Frigault0Anand Rotte1Ayub Ansari2Bradford Gliner3Christopher Heery4Bijal Shah5Massachusetts General Hospital Cancer CenterArcellx IncArcellx IncArcellx IncArcellx IncMoffitt Cancer CenterAbstract CAR-T cells are widely recognized for their potential to successfully treat hematologic cancers and provide durable response. However, severe adverse events such as cytokine release syndrome (CRS) and neurotoxicity are concerning. Our goal is to assess CAR-T cell clinical trial publications to address the question of whether administration of CAR-T cells as dose fractions reduces toxicity without adversely affecting efficacy. Systematic literature review of studies published between January 2010 and May 2022 was performed on PubMed and Embase to search clinical studies that evaluated CAR-T cells for hematologic cancers. Studies published in English were considered. Studies in children (age < 18), solid tumors, bispecific CAR-T cells, and CAR-T cell cocktails were excluded. Data was extracted from the studies that met inclusion and exclusion criteria. Review identified a total of 18 studies that used dose fractionation. Six studies used 2-day dosing schemes and 12 studies used 3-day schemes to administer CAR-T cells. Three studies had both single dose and fractionated dose cohorts. Lower incidence of Grade ≥ 3 CRS and neurotoxicity was seen in fractionated dose cohorts in 2 studies, whereas 1 study reported no difference between single and fractionated dose cohorts. Dose fractionation was mainly recommended for high tumor burden patients. Efficacy of CAR-T cells in fractionated dose was comparable to single dose regimen within the same or historical trial of the same agent in all the studies. The findings suggest that administering dose fractions of CAR-T cells over 2–3 days instead of single dose infusion may mitigate the toxicity of CAR-T cell therapy including CRS and neurotoxicity, especially in patients with high tumor burden. However, controlled studies are likely needed to confirm the benefits of dose fractionation.https://doi.org/10.1186/s13046-022-02540-wCAR-T cellsDoseEfficacySafetyTumor burden |
| spellingShingle | Matthew Frigault Anand Rotte Ayub Ansari Bradford Gliner Christopher Heery Bijal Shah Dose fractionation of CAR-T cells. A systematic review of clinical outcomes Journal of Experimental & Clinical Cancer Research CAR-T cells Dose Efficacy Safety Tumor burden |
| title | Dose fractionation of CAR-T cells. A systematic review of clinical outcomes |
| title_full | Dose fractionation of CAR-T cells. A systematic review of clinical outcomes |
| title_fullStr | Dose fractionation of CAR-T cells. A systematic review of clinical outcomes |
| title_full_unstemmed | Dose fractionation of CAR-T cells. A systematic review of clinical outcomes |
| title_short | Dose fractionation of CAR-T cells. A systematic review of clinical outcomes |
| title_sort | dose fractionation of car t cells a systematic review of clinical outcomes |
| topic | CAR-T cells Dose Efficacy Safety Tumor burden |
| url | https://doi.org/10.1186/s13046-022-02540-w |
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