Optimization of the First-Line Therapy in Primary Mediastinal (Thymic) Large B-Cell Lymphoma

BACKGROUND. The standard first-line therapies for primary mediastinal (thymic) large B-cell lymphoma (PMBCL) have not yet been clearly defined. This is a rare disease (2–4 % among all NHLs), which makes it challenging to enroll patients into large randomized studies. Most commonly, induction therapy with DA-EPOCH-R and R-CHOP regimens is used, however, no explicit advantage of one of them over the other was demonstrated by any clinical study. The role of radiotherapy (RT) in the treatment of newly diagnosed PMBCL also remains a subject to debate. Besides, there are alternative options which have proven to be effective by smaller retrospective studies, in particular, consolidation of antitumor response by high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT). AIM. To evaluate the outcomes of the first-line therapy with the standard DA-EPOCH-R and R-CHOP regimens as well as to study the feasibility of consolidating the achieved antitumor response by means of RT or HDCT with auto-HSCT in patents with newly diagnosed PMBCL in a real-world setting at one medical institution. MATERIALS & METHODS. This single-center cohort retrospective study enrolled 180 patients treated at the NN Petrov National Medical Cancer Research Center from 2013 to 2023. Most patients (n = 159) received therapy with DA-EPOCH-R regimen, R-CHOP was administered to fewer patients (n = 21). After achieving complete (CR) or partial response (PR) resulting from 6 drug therapy cycles and documented by PET/CT, patients either continued to be followed-up (n = 52) or received HDCT consolidation with auto-HSCT (n = 13) or RT (n = 64). The decision-making about the consolidation regimen was arbitrary, on researcher’s opinion. HDCT with auto-HSCT was most commonly administered to patients with stage III/IV and high IPI; RT was commonly used in patients with PR when the biopsy of the residual lesion with increased FDG uptake was technically impossible. RESULTS. In the total group, overall response rate was 76.7 % (138/180): CR 59.5 % and PR 17.2 %; in 23.3 % of cases primary refractoriness of the disease was reported. With the median follow-up of 29 months (range 17–56 months), progression-free survival (PFS) was 70.0 % and overall survival (OS) was 86.1 %. By univariate analysis of long-term outcomes, neither consolidation nor the lack of it affected PFS, which accounted for 92.3 % (HDCT with auto-HSCT), 95.3 % (RT), and 90.4 % (follow-up), respectively (p = 0.29). The evaluation of OS with and without consolidation yielded significant differences: 84.6 %, 96.9 %, and 96,2 %, respectively (p = 0.023), however, the multivariate analysis proved these data to be not significant (p = 0.06). CONCLUSION. The results of this study demonstrate the efficacy of DA-EPOCH-R regimen for PMBCL patients. After achieving CR or PR, often morphologically negative antitumor response, resulting from 6 DA-EPOCH-R cycles, the consolidation of the effect by means of RT or HDCT with auto-HSCT does not improve long-term survival rates.