Лечение пациентов с рецидивами и рефрактерным течением первичной медиастинальной (тимической) В-крупноклеточной лимфомы: собственные данные и обзор литературы
Authors: Аракелян Арман Вачаканович , Тумян Г. С. , Семенова А. А. , Кичигина М. Ю. , Заводнова И. З. , Тупицына Д. Н. , Парамонова Е. В. , Антипова А. С. , Шпирко В. О. , Ключагина Ю. И. , Рамазанова С. Ф. , Кошкина У. Г. , Монин И. С. , Золотайкина Н. М. , Петрова Г. Д. , Трофимова О. П. , Субботин А. С. , Сенченко М. А. , Кирсанов В. Ю. 
Published: January 2025

AIM. To determine the optimal strategy of chemotherapy for patients with relapsed/refractory (r/r) primary mediastinal (thymic) large B-cell lymphoma (PMBCL).
MATERIALS & METHODS. The study is based on the clinical data from 26 patients with r/r PMBCL treated at the NN Blokhin National Medical Cancer Research Center from 2010 to 2024. The patients were 20–48 years of age (median 33 years); there were 21 (81 %) women. All patients had a bulky mediastinal tumor mass (> 10 cm in maximum dimension).
RESULTS. All calculations were performed in the combined group (n = 26) which included patients with both primary refractory PMBCL (n = 21) and tumor relapses (n = 5). Refractoriness was confirmed by PMBCL progressing within less than 6 months from the completion of the first therapy program. Relapses developed during 2 years after the first-line therapy. The treatment of r/r PMBCL included the R-DHAP, R-ICE, R-BeGeV, and R-B protocols. In 24 out of 26 patients, the second- or subsequent-line salvage therapy programs included immune checkpoint inhibitor (CPI; nivolumab or pembrolizumab) and immunoconjugate (brentuximab vedotin, BV) boosts. CPIs were received by 11 (42 %) patients, and CPI + BV were administered to 13 (50 %) patients. With the follow-up median of 28 months in the total group of r/r PMBCL patients (n = 26), the 3-year progression-free survival (PFS) was 41.7 % (median 14 months), whereas the 3-year overall survival (OS) was 73.7 % (median not reached). Radiotherapy (RT) was administered to 11 (42 %) patients. The RT recipients showed the 3-year PFS of 72.7 % and OS of 100 % as compared to non-recipients with 20.3 % and 56.3 %, respectively. Autologous hematopoietic stem cell transplantation (auto-HSCT) was performed in 12 (46 %) patients. Auto-HSCT recipients showed the 3-year OS of 100 % as compared to non-recipients with 51 %.
CONCLUSION. This study demonstrated that new drugs, in particular CPI ± BV, added to the second- and subsequent-line salvage therapy protocols in r/r PMBCL can be used to overcome the primary tumor refractoriness and neutralize this extremely unfavorable factor. High-dose chemotherapy (conditioning) with subsequent auto-HSCT is clearly associated with the best long-term survival rates. By the time of drafting this paper, 12 followed-up auto-HSCT recipients remained tumor-free. In cases of RT infeasibility at the initial stage, it was mediastinal radiation in the therapy for r/r PMBCL which showed its crucial prognostically favorable value and led to considerable improvement of PFS and OS rates. In general, the capacity of chemotherapy for patients with r/r PMBCL includes CPI ± BV-boosted salvage therapy protocols as well as added auto-HSCT and RT.