Platelet and Fibrinogen Dynamics After CAR-T Cell Therapy in Relapsed/Refractory B-Cell Lymphoma May Predict ICANS Onset.

CAR-T cell therapy is efficient in relapsed/refractory B-cell lymphoma; yet, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) remain major and potentially life-threatening complications, which makes their prediction and prevention crucial. This international, retrospective study analyzed the predictive value of coagulation parameter dynamics for ICANS and CRS development in 265 B-cell lymphoma patients at two tertiary-care centers. Platelet counts, fibrinogen, PT, PTT, international normalized ratio, and D-dimer, were recorded daily from pre-lymphodepletion through 2 weeks post-infusion. ICANS occurred in 34% of patients, with high-grade events documented in 13%. Patients with ICANS had significantly lower median platelet (67 vs. 123 × 103/μL) and fibrinogen (263 vs. 379 mg/dL) levels than those without ICANS. During high-grade ICANS days, fibrinogen and platelet levels were significantly reduced (p = 0.003 and p = 1.6 × 10-14, respectively). In > 75% of high-grade ICANS cases, 1 day before its onset, platelet counts were < 100 × 109/L (median decrease: 11.6% versus 1.6% on other days; p = 0.001). Conversely, on the day preceding ICANS onset, higher fibrinogen concentrations were observed, with median values of 448 mg/dL in the ICANS group versus 376 mg/dL in the non-ICANS group (p = 0.03). These findings suggest that platelet and fibrinogen dynamics could be early indicators of ICANS development in lymphoma patients.