Of all patients, 21 (30%) experienced at least 1 infection during the first 30 days following CAR-T reinfusion. There were 11 cases of bacterial infections, 11 cases of viral infections, and 2 cases of fungal infections. There were no differences between the 2 groups in terms of infection rates.
Of the 70 patients, 50 (71%) experienced CRS, mainly of grade 1 (39%) and grade 2 (29%). Moreover, 30% of all patients experienced ICANS, mostly of grade 1 (14%). There were no differences in prevalence of CRS or ICANS between the 2 groups.
The researchers examined CAR-T expansion separately in patients treated with tisa-cel and those treated with axi-cel. For patients treated with tisa-cel, median relative Cmax CAR-T/CD3+ T cells was max 3.8% (median absolute 13 CAR-T/μL), and there were no differences between the G-CSF-group and the no–G-CSF group (median 3.6% and 13.9/μL for G-CSF vs median 4% and 5.1/μL for no–G-CSF). For patients treated with axi-cel, median relative and absolute Cmax were 17.1% and 25.2/μL with no differences between the 2 groups (median 21.1% and 28.5/μL, vs median 3.3% and 12.1/μL).
For antilymphoma activity, best overall response rate and complete response rate were 71% and 40%, with no difference between the G-CSF and non–G-CSF groups when the researchers considered the response rate at M1 (P =.89) and at M3 (P =.60). There were also no differences in overall survival (P =.86) or progression-free survival (P =.70) across cohorts.
Further analysis involving a propensity score confirmed that G-CSF administration did not influence overall survival (hazard ratio [HR], 0.45; 95% CI, 0.08-2.41; P =.35) or progression-free survival (HR, 1.09; 95% CI, 0.45-2.65, P =.84).
John F. DiPersio MD, PhD, a professor of medicine at Washington University School of Medicine in St. Louis, Missouri, who was not involved in the new research, said that he was not surprised that the administration of G-CSF did not lead to increased toxicities, because G-CSF receptors are not expressed on T cells. “There has never been any evidence that giving G-CSF in the transplant setting has ever caused increasing toxicity or graft-versus-host disease,” he said. “Even though many institutions don’t give G-CSF, it’s primarily because it’s expensive and doesn’t seem to change, overall, the outcomes and the general pace of engraftment. But toxicities have never been really significantly worsened.”
Dr DiPersio also emphasized that the mechanism of neutropenia after CAR-T cell infusion is still unclear.
Marcela V. Maus, MD, PhD, an assistant professor of medicine at Harvard Medical School in Boston, Massachusetts, who was not involved in the study, pointed out the lack of major differences between the 2 groups in the study. “The one thing that was different was the duration of hospitalization, which went from an average of 19 days to 17.5 days,” she said. “So that’s useful information, although it doesn’t seem like it’s totally game changing.”
Deciding whether to use G-CSF in the context outlined in the study is a matter of clinical judgment, Dr Maus said. “We now have the data that looks like it doesn’t make things worse, so you can have a little bit more leeway there,” she said.
Daniel W. Lee, MD, an assistant professor in the department of pediatrics at the University of Virginia in Charlottesville, who was not involved in the research, pointed out that the study was small. “But it is reassuring that, in this small study, they did not notice any differences in CRS or ICANS, and that they were able to decrease [patients’] hospitalization duration by 3 days or so,” he said.
Although the study showed no reduction in the duration of grade 3/4 neutropenia, more research involving a greater number of patients would be needed to determine whether administering G-CSF yields a benefit in this regard, he said.
Disclosures: Some authors have received honoraria or research funding from the pharmaceutical industry. Please refer to the original paper for a full list of disclosures.
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