Neuro-oncology practice · 2024
Impact of neurotoxicity and steroid therapy on cancer progression-free survival in lymphoma patients treated with anti-CD19 CAR T cells.
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Pensato Umberto, Muccioli Lorenzo, Taurino Daniela, Pondrelli Federica, Asioli Gian Maria, de Philippis Chiara, Mannina Daniele, Bagnato Gianmarco, Marcheselli Simona, Zinzani Pier Luigi, Bonifazi Francesca, Bramanti Stefania, Guarino Maria
Аннотация
BACKGROUND: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a frequent complication of chimeric antigen receptor (CAR) T-cell therapy. Most patients achieve complete symptom resolution without long-term neurological sequelae, yet the impact of ICANS and steroid therapy on oncological outcomes remains inadequately explored. We investigated the association between ICANS and steroid therapy with progression-free survival (PFS).
METHODS: We included large B-cell lymphoma patients treated with anti-CD19 CAR T cells. The primary outcome was 90-day PFS. The secondary outcomes included PFS, complete response, and overall survival (OS) at 30, 90, 180, and 365 days. The association between outcomes and ICANS and steroid treatment was assessed using logistic regression analyses adjusted for baseline factors.
RESULTS: Overall, 241 patients were included. The median age was 60 years (interquartile range [IQR] = 51-66), 81 (33.6%) were females, 67 (27.8%) developed ICANS, and 142 (58.9%) achieved 90-day PFS. There was no association between 90-day PFS and ICANS development (adjusted odds ratio [aOR] 1.39 [95% confidence interval {CI} = 0.75-2.61]), maximum grade (aOR 1.24 [0.97-1.59]), duration (aOR 1.00 [95% CI = 0.95-1.05] per 1-day increase), or day of onset (aOR 0.98 [95% CI = 0.86-1.11] per 1-day increase). There was no association between 90-day PFS and steroid therapy (aOR 1.25 [95% CI = 0.73-2.14]) or cumulative dose (aOR 1.00 [95% CI = 0.98-1.01] per 100-mg increase). Similar results were observed for secondary outcomes, except for an association between ICANS and OS at 30 days (aOR 0.05 [95% CI = 0.01-0.54]) and 90 days (aOR 0.35 [95% CI = 0.15-0.80]).
CONCLUSIONS: Our findings suggest that ICANS and steroid therapy do not adversely impact the PFS in lymphoma patients receiving anti-CD19 CAR T cells. Yet, ICANS might be associated with reduced early OS.
METHODS: We included large B-cell lymphoma patients treated with anti-CD19 CAR T cells. The primary outcome was 90-day PFS. The secondary outcomes included PFS, complete response, and overall survival (OS) at 30, 90, 180, and 365 days. The association between outcomes and ICANS and steroid treatment was assessed using logistic regression analyses adjusted for baseline factors.
RESULTS: Overall, 241 patients were included. The median age was 60 years (interquartile range [IQR] = 51-66), 81 (33.6%) were females, 67 (27.8%) developed ICANS, and 142 (58.9%) achieved 90-day PFS. There was no association between 90-day PFS and ICANS development (adjusted odds ratio [aOR] 1.39 [95% confidence interval {CI} = 0.75-2.61]), maximum grade (aOR 1.24 [0.97-1.59]), duration (aOR 1.00 [95% CI = 0.95-1.05] per 1-day increase), or day of onset (aOR 0.98 [95% CI = 0.86-1.11] per 1-day increase). There was no association between 90-day PFS and steroid therapy (aOR 1.25 [95% CI = 0.73-2.14]) or cumulative dose (aOR 1.00 [95% CI = 0.98-1.01] per 100-mg increase). Similar results were observed for secondary outcomes, except for an association between ICANS and OS at 30 days (aOR 0.05 [95% CI = 0.01-0.54]) and 90 days (aOR 0.35 [95% CI = 0.15-0.80]).
CONCLUSIONS: Our findings suggest that ICANS and steroid therapy do not adversely impact the PFS in lymphoma patients receiving anti-CD19 CAR T cells. Yet, ICANS might be associated with reduced early OS.