Association between Brain-to-Vein Time and Disease Characteristics and Outcomes for Commercial CAR T-Cell Therapy in Multiple Myeloma

Introduction:

Chimeric antigen receptor (CAR) T-cell therapy is a novel immunotherapy for advanced multiple myeloma (MM) involving genetic modification of a patient's T-cells to generate the CAR product. CAR T-cell products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) demonstrated superior outcomes over standard care, leading to FDA approval. However, there can be delays from insurance approval to T-cell collection (brain-to-vein time, B2V) and from T-cell harvest to infusion (vein-to-vein time, V2V).

This study analyzed B2V and V2V times for CAR T-cell therapy in MM, their interaction with insurance status and disease characteristics, and their impact on outcomes.

Methods:

We conducted a retrospective study of 64 consecutive insured patients at the University of Chicago collected for commercial CAR T-cell therapy between April 2021 and June 2024. Cox proportional hazard models estimated hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS), indexed from the time of T-cell collection.

Results:

There were 40 patients with Medicare and 24 patients with private insurance. Baseline characteristics were comparable across insurance types, with private group being younger in age (median 60 vs 71 years), receiving a higher proportion of cilta-cel infusions (96% vs 70%), and receiving more bridging therapy (100% vs 75%).

Median B2V times were 29.5 days (Medicare) and 39.5 days (private) (p=0.02), and a B2V time <15 days in 23% (Medicare) vs 4% (private) (p=0.049). Median V2V times were 62 days (Medicare) and 59 days (private) (p=0.78).

With a median follow-up time from T-cell collection of 9.5 months for the entire cohort, there were a total of 25 progression events and 21 deaths: 5 patients died prior to receipt of CAR T-cell therapy, 8 died directly from complications of CAR T-cell therapy, and 8 died following disease progression. 1/10 patients with a B2V <15 days died before receiving CAR T-cell therapy vs 9/54 (17%) with B2V >15 days.

On univariate analysis, the following variables were significantly associated (p<0.05) with inferior PFS and OS: receipt of ide-cel, ECOG performance status, aggressive disease features, prior BCMA directed therapy (PFS only), bone marrow plasmacytosis >60%, and ferritin > median (285). Insurance type and age were not significantly associated with PFS or OS.

Age-adjusted multivariate analysis revealed that younger age (HR 1.05, p=0.03), ide-cel vs cilta-cel (HR 3.9, p=0.007), worse ECOG PS (HR 1.9, p=0.02), prior BCMA-directed therapy (HR 5.9, p<0.001), and bone marrow plasmacytosis >60% (HR 3.3, p=0.02) were associated with worse PFS. Only worse ECOG PS (HR 2.8, p=0.002) was associated with worse OS.

Conclusions:

Patients with Medicare had numerically shorter B2V time, and a higher proportion had a B2V <15 days. While a shorter B2V time may be associated with a lower risk of dying before receiving CAR T-cells, neither insurance type, B2V time, nor V2V time were associated with outcomes overall.Multivariate analysis showed that younger age, receipt of ide-cel vs cilta-cel, worse ECOG PS, receipt of BCMA-directed therapy, and BMPC >60% were associated with worse PFS.

No relevant conflicts of interest to declare.