Serum Albumin As an Early Predictor of Survival in Patients Receiving Antibody-Drug Conjugates.

e15041 Background: Decreased baseline and cycle 1 (C1) serum albumin (ALB) predicts shorter overall survival (OS) in pts with NSCLC treated with IgG based immune checkpoint inhibitors (ICIs) but not in pts on ICI + chemotherapy. Decreased ALB may serve as a marker of hyper catabolism associated with cancer cachexia and elevated clearance (CL) of IgG drugs. It is unknown if ALB associates with OS in pts treated with antibody drug conjugates (ADCs), which combine IgG and chemotherapy. In this single-center retrospective analysis, we aimed to assess ALB and OS association. Methods: 601 cancer pts who received ADC, with at least one pretreatment and one on-treatment (C1) ALB value were included. Normal ALB was ≥ 3.5 g/dL per institution cut-off. In a subset of pts with pretreatment ALB measured within 30 days prior to start of ADC (n = 503), ALB percent change was calculated relative to the C1 value. ALB change was categorized as Increase/No change/Decrease and ( > 0%, 0% to –5%, –5% to –10%, < –10%). OS was defined as time from first ADC dose to death/censoring at most recent contact. Cox proportional hazards regression assessed ALB percent change vs. OS, adjusted for ADC and cancer type. Effect modification by ADC and cancer was evaluated with interaction terms (e.g. ADC x ALB change). Kaplan-Meier plots were used to visualize differences in OS. Results: In the full dataset (n = 601), pretreatment and C1 ALB were strongly associated with OS. Pts with normal (n = 490) vs. low ( < 3.5 g/dL, n = 111) C1 ALB had median OS of 31 mo vs. 9.8 mo, respectively (p < 0.0001). Among pts with relevant pre-treatment ALB (n = 503), pts with ALB increase had median OS of 29.3 mo, while pts with 0 – 5%, 5-10% or ≥10% decrease had median OS of 23.4 mo, 17.7 mo, and 12.1 mo, respectively ( p < 0.001). In multivariable analysis, each 10% ALB increase associated with 22% reduction in hazard of death (HR = 0.78, 95% CI 0.67–0.92). Compared with pts experiencing ≥10% ALB decrease, those with smaller decrease or increase had significantly lower hazards (adjusted HRs 0.45–0.49, all p < 0.001); highlighting the strong association of large ALB drop on survival. Borderline and significant interactions were observed comparing ALB (% change) vs cancer type (p = 0.06) and ALB change (3 categories) vs ADC type (p = 0.046), respectively. Conclusions: Early ALB change was independently associated with OS in cancer pts receiving ADCs, suggesting it may serve as an early indicator of mechanisms underlying IgG-based therapy resistance. Given known link between ALB and CL of IgG-based drugs, further investigation into the CL patterns, toxicities and outcomes of pts treated with ADCs is warranted. Age; Male(n), Female (n) 58 (24–89); 91, 510 Breast cancer, n (%) 402 (67) Non-breast, n (%) 199 (33) Advanced stage (3 - 4), n (%) 231 (38) Stage ≤ 2, n (%) 284 (47) Stage unknown, n (%) 86 (14) Trastuzumab Emtansine, n (%) 210 (35) Trastuzumab Deruxtecan, n (%) 147 (25) Enfortumab Vedotin, n (%) 91 (15) Other ADC, n (%) 153 (26)