Work

Defining the Optimal Post-CART Monitoring Period in Recipients of Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel: A Cell Therapy Consortium Study

Year: 2024

Type: article

Abstract: Rigorous monitoring in the proximity of the authorized treating center for 4 weeks after chimeric antigen receptor T-cell therapy (CART) is mandated by the US Food and Drug Administration Risk Evaluation and Mitigation Strategy /REMS program, due to the potentially fatal toxicity risks of CRS and ICANS. However, the physical and financial burden of stringent monitoring may pose a barrier to access and treatment management. Therefore, determining the optimal duration of CRS and ICANS monitoring is an area of unmet need. We evaluated outcomes for commercial axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel) recipients. Adult patients (pts) with lymphoma who received axi-cel, tisa-cel, or liso-cel between April 2016 and May 2023 were identified from the Cell Therapy Consortium registry, representing nine academic US medical centers. Descriptive analysis was used to report outcomes. New-onset events were reported as a percentage of pts at risk. A total of 475 pts were included: 216 (45%) axi-cel, 158 (33%) tisa-cel, and 101 (21%) liso-cel. Any-grade CRS occurred in 60% of pts, most common in axi-cel (80%), followed by liso-cel (49%), then tisa-cel (41%), p<0.0001. The median time to CRS onset was 3 (1-4) days. D0-7: CRS occurred in 57% of pts (75% axi-cel, 40% tisa-cel, 47% liso-cel). CRS onset D8-14 was seen in 4% of pts (15% axi-cel, 4% liso-cel, 1% tisa-cel). There was no new onset CRS beyond D14. The median time to resolution was 4 days. Notably, unresolved CRS beyond D14 occurred in 6% (9% axi-cel, 4% liso-cel, 3% tisa-cel), and only 1.4% of pts (all axi-cel recipients) had unresolved CRS beyond D28. 98.6% of CRS resolved by D28. Any-grade ICANS occurred in 32% of pts, most common in axi-cel (52%) recipients, followed by liso-cel (26%), then tisa-cel (10%), p<0.0001. The median time to ICANS onset was 5 (4-7) days. D0-7: ICANS occurred in 25% of pts (41% axi-cel, 19% liso-cel, 8% tisa-cel). ICANS onset D8-14 was seen in 9% of pts (19% axi-cel, 9% liso-cel, 1% tisa-cel,). There was one case of new onset ICANS after D14, in a tisa-cel patient. The median time to resolution was 5 days. Unresolved ICANS beyond D14 occurred in 13% (18% axi-cel, 8% tisa-cel, 8% liso-cel) and beyond D28 in 3% of pts (4% axi-cel, 1% tisa-cel, 1% liso-cel). 97% of ICANS resolved by D28. This is the largest real-world multicenter analysis that reveals negligible incidence of CRS and ICANS onset beyond 2 weeks after CART infusion, in recipients of axi-cel, tisa-cel, and liso-cel. This data supports investigating individualized CRS and ICANS monitoring periods and earlier transition for stable pts, taking into consideration other late adverse effects such as prolonged cytopenia and infections. Stringent CRS monitoring and ICE score evaluation in stable patients yield little or no benefit after day 14.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2023.12.268