68Ga-Pentixafor PET/CT-Based Response Evaluation and its Prognostic Value in Multiple Myeloma: Comparison With IMWG and 18F-FDG-Based Response.

Abstract

Purpose: 68Ga-Pentixafor PET/CT targets CXCR4 receptors and provides superior diagnostic accuracy in multiple myeloma (MM) compared with 18F-FDG PET/CT. However, its role in response evaluation remains unexplored. We propose a 68Ga-Pentixafor PET/CT-based response evaluation criterion and evaluate its utility compared with International Myeloma Working Group (IMWG) criteria and 18F-FDG PET/CT-based response.

Patients and methods: In this prospective single-center study, 40 treatment-naive myeloma patients were recruited between February 2021 and April 2023. Both 68Ga-Pentixafor and 18F-FDG PET/CT were performed at baseline and at follow-up (7.2 mo-median). Response to treatment was evaluated using the proposed 68Ga-Pentixafor PET/CT criteria and compared with responses assessed by IMWG and 18F-FDG PET/CT. Progression-free survival (PFS) and overall survival (OS) were analyzed and compared using Kaplan-Meier survival curves.

Results: Among the 40 newly diagnosed MM patients [median age: 56.5 years (IQR 45.25 to 63.75); 24 men], 68Ga-Pentixafor PET/CT was positive in a greater proportion of patients than 18F-FDG PET/CT [90% (36/40) vs. 67.5% (27/40); P=0.02] thus, adequately evaluated response in additional 27.5% (11/40) of cases. Using the proposed criteria for 68Ga-Pentixafor PET/CT, significant differences in PFS were observed across response categories [complete response (CR)-not reached, partial response (PR)-26.2 mo, progressive disease (PD)-15.3 mo; P=0.001]. Among patients achieving ≥very good partial response (VGPR) as per IMWG, those with positive 68Ga-Pentixafor PET/CT had shorter PFS compared with those with negative findings (median PFS: 34.2 mo vs. not reached; P=0.056), whereas no significant difference was noted with 18F-FDG PET/CT (P=0.68). In addition, on follow-up of patients with negative 18F-FDG at the response, those with discordant 68Ga-Pentixafor findings had significantly shorter PFS (17.73 mo vs. not reached; P=0.010) compared with those with concordant negative findings.

Conclusions: 68Ga-Pentixafor PET/CT offers a more accurate assessment of treatment response and prognosis in MM patients, adding valuable information beyond the IMWG and 18F-FDG PET/CT-based criteria.