Abstract:

Background and purpose: Next generation sequencing-identified genetic alterations of diffuse large B cell lymphoma (DLBCL) and baseline SUV_max detected by ¹⁸F-FDG PET/CT were correlated with patients’ prognosis. However, their relationship and the associations with R-CHOP response of DLBCL are still unclear. This study aimed to analyze the association bewteen genetic alterations and ¹⁸F-FDG PET/CT SUV_max and their correlations with clinicopathological characteristics and R-CHOP response of DLBCL. Methods: A total of 225 cases of primary DLBCL detected by next generation sequencing using 481 lymphoma gene panel and examined by ¹⁸F-FDG PET/CT before treatment between 2022 and 2023 were collected. This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center (Ethical No.: 050432-4-2307E) and acquired the informed consent of the patients. The translocations of BCL2, BCL6 and MYC were identified by fluorescence in situ hybridization. The clinicopathological characteristics and the PET/CT scan after R-CHOP chemotherapy were collected. Results: Finally, 191 patients were enrolled in this study. The frequency of MYD88 mutation, TP53 mutation, copy number variations of CDKN2A/2B, CD79B mutation in the 191 DLBCL patients were 24.6%, 27.2%, 32.5% and 16.8%, respectively. The range of baseline SUV_max was 5.10-63.10 (24.44±10.70, median 22.80). The baseline SUV_max of MYD88^L265P DLBCL was significantly higher than that of MYD88 wild type (P=0.039). There were no significant associations of SUV_max with other gene alterations including TP53 mutation, CDKN2A/B loss, CD79B mutation, KMT2D mutation, TNFAIP3 mutation, B2M mutation, EZH2 mutation, BTG1/2 mutation, CREBBP mutation, gene translocations of MYC, BCL2 and BCL6. The higher SUV_max before treatment was correlated with higher serum lactate dehydrogenase (LDH) level (P=0.012) and non-germinal center B-cell-like (non-GCB) DLBCL (P=0.040). However, there was no significant association of SUV_max with R-CHOP response (P=0.714). TP53 mutation was significantly associated with the poor response of R-CHOP (P=0.001) and was an independent predictor of non-complete metabolic response (non-CMR). TP53 mutation combined with Ann Arbor stage, International Prognostic Index (IPI) score and serum LDH level could better predict R-CHOP response than each factor alone. Conclusion: MYD88^L265P DLBCL had higher baseline ¹⁸F-FDG PET/CT SUV_max. The baseline SUV_max was not associated with R-CHOP response. However, TP53 mutation was significantly correlated with poor response of R-CHOP in DLBCL patients. TP53 mutation combined with clinicopathological characteristics could better predict R-CHOP response. The associations of gene alterations and SUV_max with prognosis of DLBCL patients needed to be explored in the future.

Key words: Diffuse large B cell lymphoma, Genetic alterations, ¹⁸F-FDG PET/CT, SUV_max, R-CHOP, Therapeutic response