Pre-Lymphodepletion Endothelial Activation and Stress Index As a Predictor of Clinical Outcomes in B-Cell Maturation Antigen CAR T Therapy for Multiple Myeloma

Introduction The Endothelial Activation and Stress Index (EASIX) (creatinine [mg/dL] × lactate dehydrogenase [U/L])/platelets [109 cells/L]) is a marker of endothelial damage with relevance in CAR T related toxicities. A previous study associated EASIX and ferritin (EASIX-F) with CRS grades 2-4, and EASIX combined with ferritin and CRP (EASIX-FC) with ICANS grades 2-4 in Axi-cel-treated lymphoma patients (pts). However, their use in multiple myeloma (MM) pts receiving B-cell maturation antigen (BCMA) CAR T therapy is unclear. Method We retrospectively reviewed 51 MM pts who received BCMA CAR T (40 Ide-cel, 11 investigational CAR T, 0 Cilta-cel) from April 2018 to 2023. EASIX-F and EASIX-FC calculated per the original publication (PMID: 34264268). We estimated the cumulative incidence (CI) of CRS and ICANS starting from the infusion date, considering death before toxicity as a competing risk. Univariate Cox-regression was conducted using SPSS v.29. Results Median age at CAR T was 66 years (range, 36-78), with 65% males. Revised International Staging System stages: I (31%), II (49%), III (12%), unknown (8%). High risk cytogenetics (IMWG definition): 24%. Median prior therapy: 6 lines. CRS occurred in 90% of pts (22% grades 2-4). ICANS occurred in 12% (8% grades 2-4).In EASIX-F at pre-LD, 29 pts were low, 16 intermediate, and 5 high risk. CI of CRS grades 2-4 was 24%, 25%, and 0% at 30 days in low, intermediate, and high-risk groups, respectively (p=0.49). In EASIX-FC at pre-LD, 22 pts were low, 14 intermediate, and 9 high risk. CI of ICANS grades 2-4 was 0%, 21%, and 11% at 30 days in low, intermediate, and high-risk groups, respectively (p=0.08).No significant associations in incidence or severity were observed between EASIX-F and CRS or EASIX-FC and ICANS, differing from prior findings (Fig 1). This may be the result of a limited sample size, low rates of severe CRS (22%) and ICANS (8%), and differences in the patient population (MM vs lymphoma).Median follow up was 12 months (mon). Response data was available for 86% of pts. There was a trend towards, but no significant difference for, fewer complete responses (CRs) at 3 mon according to EASIX-F and EASIX-FC, with no high-risk patients achieving CRs. The overall response rates (ORR) at 3 mon were notably lower in high-risk EASIX-F (25% high, 92% intermediate, 89% low; p=0.03) and EASIX-FC (62.5% high, 100% intermediate, 81% low; p=0.08) groups. Progression-free survival (PFS) was also lower in high-risk EASIX-F (2.5 mon high, 6.5 mon intermediate, 12.6 mon low; p<0.001) and EASIX-FC (4.1 mon high, 7 mon intermediate, 12.6 mon low; p=0.019) groups compared to low risk (Fig 2). Conclusion No significant associations were found between pre-LD EASIX-F and CRS and EASIX-FC and ICANS after BCMA CAR T, possibly due to limited sample size. However, ORR and PFS were significantly lower in high-risk compared to low-risk groups. Further, larger studies are warranted.