Response-Adapted Strategy in the Treatment of Primary Mediastinal Large B-Cell Lymphoma: Results of a Prospective Single-Center Clinical Trial

BACKGROUND. Up to now, neither the optimal treatment regimen for primary mediastinal large B-cell lymphoma (PMBCL), nor poor/favorable prognostic factors for risk stratification at the disease onset have been found. The prognosis of PMBCL is determined by the depth of metabolic response by the time of treatment completion, which underlies a response-adapted strategy. Besides, PMBCL is an aggressive tumor occurring more commonly in young women of reproductive age, which requires the development of treatment strategy during pregnancy. AIM. To assess the efficacy of the response-adapted strategy in PMBCL treatment based on the DA-EPOCH-R program in remission induction with drug dose escalation and without subsequent radiotherapy, if a complete metabolic response is reported by PET-CT. MATERIALS & METHODS. This prospective single-center clinical trial enrolled 154 patients in the period from November 2012 to March 2023. The median age of the patients was 34 years (range 19–68 years). There were 51 (33.1 %) men and 103 (66.9 %) women, 11 of whom were at various gestational ages of pregnancy. RESULTS. The response-adapted treatment was completed in all 154 patients. Overall response was 93.5 % (144/154), complete remission was 78.6 % (121/154), and partial remission was 14.9 % (23/154). Progression was reported in 6.5 % (10/154) of patients. With a follow-up of 60 months, the overall, disease-free, progression-free, and event-free survival rates were 93 %, 98 %, 92 %, and 76 %, respectively. The median was not reached. Prior to chemotherapy, 11 pregnant women aged 21–37 (median 29 years) had been assessed. By the time of PMBCL diagnosis, the gestational age of them varied from 9 to 37 weeks (median 26 weeks). Immunochemotherapy was administered to 9 women during pregnancy. At the gestational age of 27–38 weeks (median 34 weeks) delivery was reported in 10 patients who gave birth to 11 children. The children showed no malformations. All women with PMBCL diagnosed during pregnancy and all their children had been followed-up by the time of this publication. CONCLUSION. The response-adapted strategy of PMBCL treatment with the DA-EPOCH-R regimen and drug dose escalation showed a high immediate and long-term efficacy as well as tolerable toxicity, which provided ground for the decision against radiotherapy, if a complete metabolic response was reported by PET-CT. The results of this trial establish the main goal of treating aggressive lymphomas during pregnancy which is saving of two lives. Delivery of newborns without malformations despite immunochemotherapy justifies the use of the DA-EPOCH-R program at the gestational age > 12 weeks.