Investigating the association between peak post-infusion absolute lymphocyte count (ALC) and delayed toxicity in myeloma (MM) patients (pts) receiving cilta-cel.

7522 Background: Movement and neurocognitive treatment emergent adverse events (MNTs), cranial nerve palsies (CNPs) and immune-effector cell enterocolitis (IEC-EC) are late onset toxicities associated with cilta-cel and are associated with significant morbidity and mortality. We aimed to identify predisposing risk factors to allow for formulating risk-reduction strategies. Methods: Retrospective study of MM pts who received FDA approved cilta-cel at Mayo Clinic between Feb 2022-Dec 2024. Interrogated factors included demographics, disease and treatment characteristics, and selected lab values at different time points. In odds ratio (OR) analyses, pts were divided by toxicity type (1) No delayed toxicity (2) MNT (3) IEC-EC without MNT (4) isolated CNP. Differences between pts in the MNT, IEC-EC and CNP groups were compared separately in a pairwise manner vs. those with no delayed toxicity. Results: Of 235 pts, 26 (11%) had delayed toxicity [MNT = 8 (3%), IEC-EC = 9 (4%), CNP = 14 (6%)]; 3 pts had both MNT/IEC-EC and 2 had both CNP/IEC-EC. Median onset from CAR-T infusion for MNT, IEC-EC and CNP was 19 (range 8-96), 106 (35-169) and 21 (7-43) days respectively. Of 164 evaluable pts, those who had ICANS had increased odds for any delayed toxicity (OR 4.7; 95% CI 1.6-13.8). Pts who had ICANS (OR 7.7; 1.6-36.9), HLH/MAS (OR 6.2; 1.1-6.7) and Ferritin >400mcg/L at time of lymphodepletion (OR 6.3; 1.5-32) had increased odds for MNTs. Pts who received alkylator-based bridging therapy had increased odds (OR 6.1; 1.1-35) for IEC-EC. Analysis of serial post-CAR infusion lab values showed that peak ALC was the most significant variable with differences between groups shown in table. Median time to peak ALC was 12 days (IQR 11-13). ROC analysis determined peak ALC >3 x 10 9 /L as a meaningful cut point. Pts with peak ALC >3.0 x 10 9 /L had increased odds of developing any delayed toxicity (OR 9.3; 3.5-29.3), MNT and CNP (table). Absolute risk of any delayed toxicity was 33% in pts with peak ALC >3 x 10 9 /L vs 5% without. At this threshold, number needed to treat was 3.6. Conclusions: Real-world data shows that cilta-cel associated delayed toxicity is seen in ~10% of patients, with specific toxicity rates between 4-8%. Factors associated with these toxicities predominantly occur in the post CAR-T infusion period. Given that ALC expansion in the first 2 weeks correlate with CAR-T expansion, peak ALC is potentially predictive of toxicity and 3 x 10 9 /L may be an interventional threshold for primary prophylaxis. Peak ALC by toxicity groups. No ToxN=138 MNTN=8 CNPN=12 IEC-ECN=6 p value Peak ALC (10 9 /L), median (IQR) 1.8 (1.0-4.1) 6.2 (4.8-14.4) 4.3 (3.2-6.7) 3.6 (1.9-5.2) <0.001 1 ALC >3 x 10 9 /L, n (%) 43 (31%) 7 (88%) 10 (83%) 4 (67%) <0.001 2 Odd Ratios vs no Tox 3 , 95% CI 15.5 (2.6-293.7) 11.0 (2.8-73.9) 4.4 (0.8-25.0) 1 Wilcoxon/Kruskal-Wallis Tests, 2 Chi square test, 3 Logistic regression analysis.