Investigating metabolic connectivity in patients with multiple myeloma receiving BCMA CAR T cell therapy.

Abstract

7524 Background: BCMA-targeted CAR T cell therapy is a highly effective treatment for patients with relapsed/refractory multiple myeloma (MM) with side effects such as CRS, ICANS, and movement and neurocognitive toxicities (MNTs). Regional changes on [ 18 F]fluoro-deoxy-2-D-glucose PET (PET) can be used to derive metabolic connectivity, an emerging technique that models brain function from the uptake on a PET, allowing us to investigate alterations of regional metabolism (SUV) and changes in metabolic brain networks (connectivity) peri-CAR T. Methods: Patients were included in this retrospective study if they were treated with commercially available BCMA-directed CAR T cells and had pre-and post-CAR therapy PET imaging. We analyzed the connectivity of the whole brain and parcellated the brain to generate global and regional connectivity matrices and investigated the association of regional metabolic differences and differences in metabolic connectivity with clinical parameters. Results: Of the 108 consecutive patients (65 Cilta-cel, 43 Ide-cel), there were 61 men and 47 women (median age 65), with PET a median of 12 days prior to infusion 28 days post infusion. Toxicities included CRS alone (n=66), CRS + ICANS (n=8), CRS+facial palsy (n=3), and CRS + Parkinsonism + facial palsy (n=2). Within the entire cohort, a significantly higher SUV-mean was noted in putamen (p<0.0004) post-CAR T compared to pre-CAR T, with other brain regions not showing a difference. These regional differences were significantly and inversely associated with the grade of ICANS (Post-Pre: Left: t=-1.76, p=0.08; Right t=-2.1 p=0.04). When comparing patients with (n = 79) and without (n=29) any post-CAR T cell CRS/ICANS/MNT, the post SUV-mean was significantly higher in the bilateral basal ganglia (BG) of patients who experienced toxicity (p<0.05). The SUV-mean was significantly lower in the bilateral inferior frontal opercularis, triangularis, and bilateral Rolandic operculum of those who developed ICANS (Grade 1-2, all with CRS, n=8) vs with CRS alone (all grade 1, n=46) (p<0.05). Globally, the metabolic connectivity network had less efficiency (post<pre: 0.69<0.75), and density (post<pre: 63<74). In local measurements, post-CAR T cell PET showed significantly lower local efficiency (p=10 -30 ), degree (p=10 -15 ), strengths (p=0.001), clustering coefficient (p=10 -12 ), and higher edge betweenness centrality (p=0.02) compared to the pre-CAR T timepoint. The decreases in network measurement were more severe in the frontal lobe and basal ganglia (p=10 -6 and p=0.004, respectively). Conclusions: Patients with neurotoxicity after BCMA CAR T had an increased SUV in the putamen, but decreased in the frontal regions and basal ganglia at Day 28. Metabolic networks were globally less efficient and less dense and have changes that signify injury or attempts at compensation.