Reduced splenic uptake on 68Ga-Pentixafor-PET/CT imaging in multiple myeloma - a potential imaging biomarker for disease prognosis

Beyond being a key factor for tumor growth and metastasis in human cancer, C-X-C motif chemokine receptor 4 (CXCR4) is also highly expressed by a number of immune cells, allowing for non-invasive read-out of inflammatory activity. With two recent studies reporting on prognostic implications of the spleen signal in diffusion-weighted magnetic resonance imaging in patients with plasma cell dyscrasias, the aim of this study was to correlate splenic Ga-68-Pentixafor uptake in multiple myeloma (MM) with clinical parameters and to evaluate its prognostic impact. Methods: Eighty-seven MM patients underwent molecular imaging with Ga-68-Pentixafor-PET/CT. Splenic CXCR4 expression was semi-quantitatively assessed by peak standardized uptake values (SUVpeak) and corresponding spleen-to-bloodpool ratios (TBR) and correlated with clinical and prognostic features as well as survival parameters. Results: Ga-68-Pentixafor-PET/CT was visually positive in all MM patients with markedly heterogeneous tracer uptake in the spleen. CXCR4 expression determined by Ga-68-Pentixafor-PET/CT corresponded with advanced disease and was inversely associated with the number of previous treatment lines as compared to controls or untreated smouldering multiple myeloma patients (SUV(peak)Spleen 4.06 +/- 1.43 vs. 6.02 +/- 1.16 vs. 7.33 +/- 1.40; P < 0.001). Moreover, reduced splenic Ga-68-Pentixafor uptake was linked to unfavorable clinical outcome. Patients with a low SUV(peak)Spleen (<3.35) experienced a significantly shorter overall survival of 5 months as compared to 62 months in patients with a high SUV(peak)Spleen >5.79 (P < 0.001). Multivariate Cox analysis confirmed SUV(peak)Spleen as an independent predictor of survival (HR 0.75; P = 0.009). Conclusion: These data suggest that splenic Ga-68-Pentixafor uptake might provide prognostic information in pre-treated MM patients similar to what was reported for diffusion-weighted magnetic resonance imaging. Further research to elucidate the underlying biologic implications is warranted.

Automated summary

This study evaluates the prognostic impact of splenic CXCR4 expression in patients with multiple myeloma (MM). The findings suggest that splenic Ga-68-Pentixafor uptake is associated with disease progression, treatment history, and clinical outcome. Reduced splenic uptake is linked to unfavorable prognosis and can serve as an independent predictor of survival.