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The 2022 Tandem Meetings | The impact of G-CSF on CAR-T therapy recipients

Muhammad Bilal Abid, MD, MRCP, Medical College of Wisconsin, Milwaukee, WI, comments on the use of G-CSF in the context of CAR-T therapy. Dr Abid explains that although studies are suggesting that this growth factor may significantly increase the incidence, severity, and duration of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) whilst marginally decreasing the incidence of infections, the data is conflicting and limited. Moving forward, Dr Abid describes the design of a study that could assess the impact of G-CSF on patient outcomes, mentioning key clinically meaningful endpoints. This interview took place at the Transplantation & Cellular Therapy (TCT) Meetings of ASTCT™ and CIBMTR® 2022 in Salt Lake City, Utah.

Transcript (edited for clarity)

Primarily, use of G-CSF in CAR-T, the data on it has been limited, have been limited and conflicting in CAR-T setting. That primarily sense of the fact that G-CSF could exacerbate the incidence, severity, and duration of CRS and ICANS via myeloid precursors, antigen-presenting cell function, and induction of pro-inflammatory cytokines. A handful of small single center studies have shown that while G-CSF may decrease the infections and that to in a non-statistically significant manner, the severity and duration of CRS was significantly increased with this use...

Primarily, use of G-CSF in CAR-T, the data on it has been limited, have been limited and conflicting in CAR-T setting. That primarily sense of the fact that G-CSF could exacerbate the incidence, severity, and duration of CRS and ICANS via myeloid precursors, antigen-presenting cell function, and induction of pro-inflammatory cytokines. A handful of small single center studies have shown that while G-CSF may decrease the infections and that to in a non-statistically significant manner, the severity and duration of CRS was significantly increased with this use. Also, G-CSF utilization vary across centers. And additionally, large body guidelines have been conflicting and product inserts are unclear. One large axi-cel and tisa-cel, one of them does not comment on use of myeloid growth factors at all. While the other one, really limits its use until complete resolution of CRS. Until we have more data, it is recommended to not consider myeloid growth factors in CAR-T setting, until we get large body of data, either registry-based analysis or a best case scenario, prospective randomized trial results.

This CIBMTR proposal, we hypothesize that G-CSF usage shortens the duration of neutropenia, and may decrease the incidence of infections. We also hypothesize that G-CSF use is associated with an increased incidence, severity, and duration of CRS and ICANS. G-CSF use after CAR-T infusion does not impact one year outcomes, particularly response outcomes and survival outcomes. I think a meaningful way to examine this systematically would be to conduct a prospective randomized study, or a large multicenter study. Short of that, registry database that collects data prospectively could be utilized in the interim. And CIBMTR data provides great opportunity in that regard. If such a study is designed, some of the clinically meaningful primary endpoints could include CRS all grade and high grade, graded according to the standard ASTCT criteria, as well as ICANS examined in the similar manner with death as competing risk. Some of the secondary endpoints could include infection endpoints, primarily incidence of neutropenia, time to neutrophil engraftment, and cumulative incidences and density of infections, oral, bacterial, viral, and fungal infections let’s say at landmarks, such as day plus 30 and day plus 100, compared between those who received G-CSF, versus those who did not receive G-CSF. Now lastly, some of the clinical endpoints that could include which could be examined at six months and at one year are overall survival, progression free survival, non-relapse mortality, and duration of response.

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