(PA-075) Macrophage Activation Syndrome-Like in Multiple Myeloma Patients Treated with the Academic Bcma-Directed Car-T Ari0002h: Genomic Insights and Clinical Implications

This multicentre, retrospective, analytical study evaluated MM patients treated with the anti-BCMA academic product ARI0002h. The definition of MAS-like was based on the University of California San Francisco (UCSF) consensus criteria: [1] ferritin rise ≥100 mg/L/h within 24 hours and [2] fibrinogen < 150 mg/dL or LDH >2 times the upper limit of normal or histopathological diagnosis. The primary endpoints included analysis of baseline characteristics, identification of predictive factors, and assessment of the impact on survival based on the development of MAS-like.

Results:

Among the 80 patients analysed, 12 (15%) met the UCSF criteria for MAS-like events. These patients exhibited a higher International Staging System (ISS) score at enrolment (ISS III: 54.5% vs. 15.2%; p = 0.006), elevated serum monoclonal component levels (31.3 g/L vs. 6.8 g/L; p=0.004), both of which demonstrated independent predictive value for MAS-like, and a higher prevalence of extramedullary disease (41.7% vs. 16.2%; p=0.05). In the genetic analysis, variants affecting perforin-related pathways—including mutations in the PRF1 and UNC13D genes—were identified in 16.7% of patients presenting with MAS-like. This syndrome typically began approximately 9 days after infusion, with a rise in ferritin, followed by LDH (median 11.5 days) and hypofibrinogenemia (median 14 days). One-third of patients met all three criteria, and all exhibited hypertriglyceridemia, hypertransaminasemia, and ≥2 cytopenias. Histopathological examination was positive in 5 out of 8 evaluated patients. Patients who developed MAS-like had a poorer response (complete response: 25% vs. 68%; p=0.008) and shorter median progression-free survival (PFS) and overall survival (OS) (7 months vs. 21.4 months and 18 months vs. not reached, respectively; p=0.004). Furthermore, patients who met all three UCSF criteria, compared to those who met only two, showed a poorer response (VGPR or better: 25% vs. 100%; p=0.04), as well as shorter PFS (5.5 months vs. 11.8 months; p=0.01) and OS (7.8 months vs. 21.5 months; p=0.01).

Conclusions:

MAS-like is associated with poorer responses and reduced PFS and OS, especially in patients meeting all three UCSF criteria: elevated ferritin, hypofibrinogenemia and increased LDH. High tumour burden, including elevated monoclonal component, high ISS and extramedullary disease, seems to contribute to MAS-like development.