OA-11: Utility of 18FDG-PET/CT for Risk Prediction in Relapsed/Refractory Multiple Myeloma Patients Undergoing CAR-T Cell Therapy: Analysis of Baseline and Early Assessment Scans After One and Three Months

Introduction: Chimeric antigen receptor (CAR) T-cells are an effective treatment for relapsed/refractory multiple myeloma (RRMM) patients. Unfortunately, a significant number relapse during the first two years. The predictive value of positron emission tomography/computed tomography (18FDG-PET/CT) in this group of patients has not been established. Our aim is to assess the utility of 18FDG-PET/CT for risk prediction in RRMM patients undergoing CAR-T cell therapy.

Methods: Sixty-two patients received CAR-T cell therapy between April 2018 and February 2023. 18FDG-PET/CT was performed at baseline for all patients, and 1 and 3 months after infusion for 57 (92%) and 51 (82%) patients, respectively. We analyzed the presence of focal lesions (FL), paramedullary (PMD), and extramedullary disease (EMD); bone marrow (BM) and FL uptake measured by Deauville score. 18FDG-PET/CT was positive if Deauville scores ≥4 was found for any of the previous variables.

Results: Out of 62 baseline exams, 49 (79%) were positive. At baseline the presence of hypermetabolic EMD was the only variable associated with worse progression-free (PFS) (hazard ratio [HR] 4.8 [95%CI 2.0 – 11.3; P < .001]) and overall survival (OS) (HR 2.9 [95%CI 1.2 – 6.8; P = .018]).

In terms of response evaluation, 33 out of 57 (58%) and 18 out of 51 (35%) scans were positive 1 and 3 months after infusion, respectively. A negative scan at 3 months was associated with improved PFS (median 16 months [95%CI 12 – 19] vs. 6.8 [95%CI 3.4 – 10.3]; P = .04) and OS (median 34 months [95%CI 16 – 52]; vs. 11 [95%CI 7.6 – 15]; P = .012). Interestingly, the assessment at month 1 did not detect any differences in PFS (P = .28), although it did reveal statistically significant differences in OS (median 34 vs. 13 months; P = .021).

The presence of hypermetabolic FL with Deauville = 4 did not significantly impact PFS when compared to FL with a Deauville ≤ 3 at both month 1 (median NR vs. 14.5 months; P = 0.23) and 3 (median 18 vs. 8.1 months; P = 0.33).

Furthermore, the persistence of hypermetabolic EMD at 3 months was associated with shorter PFS (HR 18.2 [95%CI 5.0 – 65.9]; P < .001) and OS (HR 5.7 [95%CI 1.8 – 18.4; P = .003]). Conversely to basal scans, persistent hypermetabolic PMD at month 3 was associated with shorter PFS (median 3.7 months [95%CI 3.6 – 3.9] vs. 14.5 [95%CI 9.0 – 19.9]; P < .001) (HR 6.2 [95%CI 1.9 – 21.1]; P = .002) and OS (median 7.8 months [95%CI 3.4 – 12.2] vs. 34.2 [95%CI 19.9 – 45.6]; P < .001) (HR 8.3 [95%CI 2.5 – 27.6]; P = .001).

Conclusions: In conclusion, our study suggests that 18FDG-PET/CT is a valuable tool for staging and prognostication in patients with RRMM treated with CAR-T cells. Based on our results, the optimal timing for response assessment is 3 months after infusion and the persistence of FL uptake with Deauville score = 4 should be evaluated with caution along with other exams.