Effect of Surgical Resection on Survival in TP53-Mutated Diffuse Large B-Cell Lymphoma Patients

Purpose: TP53 mutation was recognized as a negative prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL). Exploratory therapy for this group of patients is in great need for potential clinical benefit. Here, we investigated the effect of adding surgical procedure to standard immunochemotherapy on survival of TP53 MUT DLBCL patients. Methods: Capture-based targeted sequencing was performed on 214 DLBCL patients, of which 47 was detected TP53MUT and included for further analysis. Refractory patients were defined as individuals did not achieve complete remission (CR) or develop relapse after 6 months in response to initial treatment. Findings: For 47 patients confirmed with TP53 mutation, 44 (93·6%) received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regime were included for survival analysis with a median follow-up of 13 months. The median progression-free survival (PFS) and overall survival (OS) were 10.0 months (95%CI, 6·7-13·3) and 46.0 months (95%CI, 11·8-80·2). Among them, 26 patients developed refractory and received second-line chemotherapy. Seven limited-stage patients after early complete resection and one patient with residue resection remained event free with a median follow-up of 37 months. A multivariate analysis showed adding surgery to R-CHOP regime significantly improved PFS of TP53 MUT DLBCL patients compared to R-CHOP only treatment (p=0·039, HR=0·109, 95%CI=0·013-0·894). Conclusions: TP53 mutation is associated with unfavorable prognosis in DLBCL patients. Our study showed surgical resection may provide additional clinical benefit, which offered new treatment consideration for this group of patients. Funding Statement: This study was supported by National Key Technology Support Program (2014BAI09B12), CAMS Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001), and National New Drug Innovation Program (2017ZX09304015). Declaration of Interests: JL is an employee of Burning Rock Biotech. All other authors declare no conflicts of interest. Ethics Approval Statement: The study was approved by the local ethic committee and was conducted in accordance with the Declaration of Helsinki.