Characteristics and predictive model for diffuse large B-cell lymphoma with early chemoimmunotherapy failure

Ying-Yu Dong^1,2,3Qing Shi^1,2,3Wen Wu^1,2,3Bing-Bing Zhao⁴Di Fu^1,2,3Pengpeng XU^1,2,3Shu Cheng^1,2,3Guilhem Bousquet^5,6,7Weili Zhao^1,2,3*Li Wang^1,2,3*

• ¹Shanghai Institute of Hematology, Shanghai, Shanghai Municipality, China
• ²State Key Laboratory of Medical Genomics, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
• ³National Research Centre for Translational Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
• ⁴People's Liberation Army 411 Hospital, Hongkou, China
• ⁵Université Sorbonne Paris Nord, Villetaneuse, Île-de-France, France
• ⁶Service d’Oncologie Médicale, Hôpital Européen Georges-Pompidou (HEGP), Paris, France
• ⁷Pôle de Recherches Sino-Français en Science du Vivant et Génomique, Laboratory of Molecular Pathology, Shanghai, China

The outcomes of refractory or relapsed diffuse large B-cell lymphoma are generally poor, especially those relapsed or progressed within 12 months from diagnosis named as early chemoimmunotherapy failure (ECF), with a 2-year OS of 24.7%. Due to the dismal outcome, early recognition of ECF and developing targeted innovative treatments to improve patient prognosis are urgent. This study recruited 2038 newly diagnosed DLBCL patients treated with R-CHOP/RminiCHOP or R-CHOP-based immunochemotherapy in Ruijin hospital and 411 hospital from December 1997 to December 2020. Compared to the control group, ECF patients were significantly associated with elderly age, advanced Ann Arbor stage, elevated serum LDH, poor performance status, multiple extranodal involvements, double expressor lymphoma (DEL), and non-GCB subtype, as well as high frequencies of TP53, FOXO1 and FBXW7 mutations. Through multivariate analysis, elderly age, advanced stage, elevated serum LDH, DEL, and mutations of TP53 or FOXO1 were independent predictors of ECF. Based on these predictors, a nomogram of ECF was established, and the straining cohort of our Chinese patients as well as the external cohort from Western countries showed a good predictive power of the ECF model, indicating the efficiency of our ECF predicting model, regardless of patients' race. Our ECF model allows clinicians to early recognize ECF patients, to optimize the therapeutic strategies and to improve the outcome of those chemo-resistant patients.