P-001: Impact of Age and Frailty on Outcomes of Patients with Multiple Myeloma Receiving CAR T-Cell Therapies – A single center experience

Introduction: Despite higher incidence of multiple myeloma (MM) in older patients (pts), they are underrepresented in CAR T-cell trials. However, older pts vary in fitness level. Frailty predicts adverse outcomes with systemic therapy in MM, but impact on CAR T outcomes is not established. We conducted a retrospective study to evaluate CAR T-cell outcomes in our institution based on age and frailty.

Methods: We included adult pts with MM who received CAR T from August 2016-December 2023 as standard of care or trial. We compared outcomes of older (≥70 years [y]) vs younger pts including: best response, progression-free (PFS) and overall (OS) survival, early mortality within 90 days, and toxicity in 6 months including: cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), healthcare utilization (ED/unplanned hospitalizations), and infections. We also assessed outcomes based on frailty in pts ≥ 60y using the simplified frailty index (Facon et. al) which includes age, ECOG performance status and Charleston Comorbidity Index (CCI). A score ≥2 = frail. Unless stated, P values are insignificant.

Results: We included 257 pts. Median age was 65y (33-83y); 30% were ≥70y; 42% were female. Median follow-up was 1.8y (95%CI: 1.6-2.0). There was no significant difference in PFS (median: 1y), early mortality (4% vs 3%), or OS (median: 3.8 vs 2.4y, 1y OS: 83% vs 78%) in pts < vs ≥70y, respectively. There was no difference in CRS incidence (79% vs 86%), Grade >2 (2% vs 5%), or recurrence (5%). Patients ≥70y had earlier onset (median: 1 vs 2 days, P=0.03), and longer CRS duration (3 vs 2 days, P=0.03). For ICANS, pts < and ≥70y had similar incidence (13% vs 21%), Grade≥2 (3% vs 8%), time to onset (3 days), and duration (2 days). There was no significant difference in healthcare utilization (58% vs 64%) between the groups. Pts ≥70y had higher infection rate (29% vs 18%, P=0.047). Among pts >60y (N=248), 33% were frail. There was no difference in ≥VGPR (78%) or PFS (1y) in frail vs non frail pts. There was no significant difference in CRS incidence (86% vs 82%), Grade >2 (3% vs 4%), time to onset (1 vs 2 days), duration (3 days), or recurrence (5% vs 6%). There was no difference in incidence (23% vs 18%) or Grade >1 (9% vs 4%) ICANS, but duration was longer in frail vs non frail pts (3 vs 1 day, P=0.03). Frail pts had higher healthcare utilization (74% vs 56%, P=0.02), but similar infection (31% vs 20%) and early mortality (5% vs 4%) rates. OS was shorter in frail vs non frail pts (2.4y vs not reached, P=0.02; 1y OS: 79% vs 82%). On univariate analysis, ECOG >1 was associated with decreased OS, but age and CCI > 1 were not.

Conclusions: Older pts have higher infection rates post CAR T. Otherwise, efficacy and toxicity are similar in older vs younger pts. Frail pts have similar response and toxicity, but higher healthcare utilization compared to non frail pts. Frailty, defined by the simplified index, is associated with decreased OS but age and CCI criteria alone are not.