Correlations between Lesion Avidity, Immune Effector Cell-Associated Neurotoxicity Syndrome Scoring, and Fracture Risk in Patients with Multiple Myeloma Undergoing Chimeric Antigen Receptor T-Cell Therapy

Background:

Patients with refractory multiple myeloma (MM) may be eligible for chimeric antigen receptor T-cell (CAR-T) therapy. Such patients are monitored for treatment toxicities, commonly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Patients' skeletal disease may also be characterized by lesion avidity and categorized by fracture risk. The purpose of the present study is to evaluate the associations between treatment toxicity, fracture, and pre-CAR-T lesion avidity in MM patients.

Methods:

A prospective, consecutive cohort of (MM) patients undergoing treatment with CAR-T therapy were reviewed retrospectively. The primary outcome measure was fracture risk as characterized by a modified Mirel's criteria. The secondary outcome measure was change in lesion avidity, measured as standardized uptake value (SUV) units, on PET-CT. Correlations were performed using Pearson and Spearman correlations.

Results:

We identified 139 patients who underwent CAR-T for multiple myeloma. The mean age was 64.4 years with 58 female patients (41.7%). There was a negative correlation between ICANS Toxicity Grade and days survived (r_s=-0.322, p<0.02) and positive correlation with the lesion SUV measurements prior to CAR-T (r_s=0.375, p<0.01). No significant correlations were found with CRS. The SUV of lesions prior to CAR-T had positive correlations with pre-CAR-T Mirel's criteria of size (r_s=0.196, p<0.035), nature(r_s=0.362, p<0.000), pain(r_s=0.303, p<0.001), and overall score (r_s=0.327, p<0.000) of the lesions. There were positive correlations between fracture occurrence with pre-CAR-T Mirel's criteria of size (r_s=0.362, p<0.000), nature (r_s=0.219, p<0.012), pain(r_s=0.393, p<0.000), and overall score(r_s=0.394, p<0.000) of the lesions. Pre-CAR-T SUV values were positively correlated with fracture occurrence (r_p=0.205, p<0.025)

Conclusions:

Our findings suggest that SUV measurements may have some association with fractures and ICANS grade in MM patients undergoing CAR-T. While SUV may correlate with Mirel's criteria, it is not as strongly correlated with fractures.

Binitie:Onkos: Consultancy. Freeman:Seattle Genetics: Consultancy; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy; Abbvie: Consultancy; Sanofi: Consultancy; Incyte: Consultancy; ONK therapeutics: Consultancy; Amgen: Consultancy; Janssen: Consultancy, Research Funding; Roche/Genentech: Research Funding. Lazarides:Restor3d: Consultancy.