KEY TAKEAWAYS
- The study aimed to investigate the impact of varying LDC regimens on CAR T-cell expansion and efficacy in patients with NHL.
- Researchers noticed the feasibility of a 2-day LDC regimen with fludarabine and cyclophosphamide for CAR T-cell therapy; further investigation is ongoing.
Lymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC regimen, including dose and frequency.
David G Frame and the team aimed to assess the impact of varying LDC regimens on CAR T-cell expansion and efficacy in non-Hodgkin’s lymphoma (NHL).
Researchers performed an inclusive analysis of consecutive patients at a single institution who received LDC prior to CD19-directed CAR T-cell therapy with axicabtagene ciloleucel and tisagenlecleucel. Patients treated before May 2019 received fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2 for 3 days, while those treated thereafter received fludarabine 40 mg/m2 and cyclophosphamide 500 mg/m2 for 2 days. Clinical data from each cohort were extracted from electronic medical records and compared to evaluate differences in CAR T-cell efficacy and toxicity.
About 92 patients received LDC prior to CD19 directed CAR T-cell therapy for relapsed NHL from June 2018 to August 2023. Twenty-eight patients received a 3-day regimen, and 64 received a 2-day regimen. Overall response rates (ORR) between the 2-day and 3-day regimens were similar (69% vs 75%, P=0.21), as were complete response rates (50% vs 54%, P=0.82). There were no significant differences in grade 2-4 cytokine release syndrome (55% vs 50%, P=0.82) or grade 2-4 immune effector cell associated-neurotoxicity syndrome (42% vs 29%, P=0.25). Prolonged platelet recovery (>60 days) was more frequent with the 3-day regimen (9% vs 27%, P=0.026).
The study concluded on the feasibility of a 2-day regimen of LDC with fludarabine and cyclophosphamide, highlighting its negligible impact on CAR T-cell efficacy or toxicity. Prospective studies are essential to identify the optimal LDC regimen for CAR T-cell therapy.
The study received no funds.
Source: https://pubmed.ncbi.nlm.nih.gov/38947326/
Frame DG, Geer M, Kasha S, et al. (2024). “Comparing 2-day vs 3-day flu-CY lymphodepleting regimens for CD19 CAR T-cell therapy in patients with non-hodgkin’s lymphoma.” Front Immunol. 2024 Jun 14;15:1403145. doi: 10.3389/fimmu.2024.1403145. PMID: 38947326; PMCID: PMC11211265.
