ABCL-176 New Strategy of First-Line Treatment of Primary Mediastinal Lymphoma (PML): One Center Experience

• Published in: Clinical lymphoma, myeloma and leukemia Vol. 23; p. S422
• Main Authors: Gabeeva, Nelly, Tatarnikova, Svetlana, Koroleva, Darya, Smolyaninova, Anna, Kimaykina, Valeria, Smirnova, Svetlana, Nikulina, Elena, Gemdzhyan, Eduard, Julhakyan, Hunan, Sudarikov, Andrey, Zvonkov, Eugenie
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2023
• Subjects: AML; ctDNA; lenalidomide; NF-kB; primary mediastinal lymphoma; AML; lenalidomide; primary mediastinal lymphoma; ctDNA; NF-kB
• ISSN: 2152-2650; 2152-2669
• DOI: 10.1016/S2152-2650(23)01299-5

PML is an aggressive lymphoid tumor with a unique biology. Regardless of the first-line therapy, refractory disease can occur in up to 10% of patients and correlates with poor outcomes. The long-term toxicity of radiotherapy and the risk of recurrence with central nervous system (CNS) involvement are subjects of ongoing debate. More intensive regimens are associated with significant toxicity. We developed a hybrid protocol for the first-line treatment of PML. To improve the outcome, we integrated lenalidomide as an inhibitor of the NF-kB pathway. To assess the efficacy of twostep pilot prospective protocols PML-16 and PML-19 for untreated PML. From January 2016 to June 2022, 34 previously untreated PML patients were included (median age 32, stage >I - 60%, extramediastinal lesions -14%, bulky disease -73%). PET-CT and ctDNA were performed before CT, after 2 cycles, and after the end of CT. Our first step (PML-16 protocol) was intensifying the induction phase. Eighteen patients received treatment according to this protocol, consisting of 6 cycles: (i) induction (blocks A and B of R-mNHL-BFM-90); (ii) consolidation (4 cycles of R-EPOCH). The program was interrupted after 2-5 cycles due to prolonged cytopenia in 5/18 patients. After the end of therapy, all 18 patients achieved PET-negative remission. Given the efficacy of this approach, we developed the next step consisting of 4 cycles (PML-19): (i) induction (A and B of R-mNHL-BFM-90); (ii) consolidation with 2 courses of R-EPOCH; (iii) lenalidomide 1-10 days of each course. Sixteen patients received treatment according to the PML-19. After the end of therapy, 9 (56%) patients were PET-negative; 7 (44%) were PET-positive (D4–5 score). ctDNA was performed in 15 patients. Regardless of the PET-CT status, ctDNA was eliminated in all patients after the end of therapy. During follow-up, the PET-CT metabolic activity decreased to physiological without consolidating therapy. With a median follow-up of 36 months (9-76 months), all 34 patients are in complete remission. Our preliminary results indicate that the new approach had a high cure rate in PML patients. ctDNA is a reliable marker for response assessment in PML.