The First Experience of Treatment of Patients with Primary Mediastinal Lymphoma Using the R-m-NHL-BFM-90/R-EPOCH Protocol

Background: Primary mediastinal lymphoma (PML) is an aggressive, but curable disease. Given the rarity of disease there is no consensus on the most effective program. The most encouraging results with R-DA-EPOCH program (Dunleavy K. et al, 2013) demonstrated high response rate and improved long-term event-free (EFS) and overall survival (OS) without radiotherapy. However, in the real world setting we still face a very difficult treatment decision: on the one hand, due to increasing treatment-related toxicities about 20% of patients (pts) didn`t complete the treatment plan, on the other, approximately 10% of patients had disease progression or relapse.

Based on our own successful experience of treating aggressive B-cell lymphomas by using the previously published R-m-NHL-BFM-90 protocol, we used a strategy of intensive induction of remission (blocks A, B), followed by de-escalation of therapy with 2 or 4 courses of R-EPOCH depending of interim PET/CT (iPET/CT) results. Here we report the first results of the toxicity and efficacy assessment of the response-adapted program R-m-NHL-BFM-90/R-EPOCH for patients with untreated primary mediastinal lymphoma.

Methods: Eleven previously untreated patients (pts) with PML underwent R-m-NHL-BFM-90/R-EPOCH treatment between October 2004 and July 2015 in Federal State Budgetary Organization «National Research Center for Hematology of Russian Federation Ministry of Healthcare»; median age 34 years old (range 24-50); M\F=2\9; Ann Arbor stage >I in 11 (100%). All the patients had one or more adverse factors (bulky mediastinal disease>10 cm in 10 pts, soft tissues involvement in 7 pts, breast in 4 pts; elevated lactate dehydrogenase level in 7 pts, pleural effusion in 5 pts). The treatment plan consisted of: (i) pre-phase (dexamethasone and cyclophosphamide); (ii) induction of remission (courses A and B of NHL-BFM-90 program that was modified in the following way: the dose of methotrexate was reduced to 1500mg/m2 (12 h) in course A, doxorubicin in dose 50mg\m² was added on the third day of course A); (iii) consolidation with R-EPOCH without dose escalation (2 courses in pts with negative iPET/CT (DS1-3) and 4 courses in pts with positive iPET/CT (DS 4-5)).

Results: All the patients completed the treatment plan. Hematologic toxicity grade 3-4 was observed only during the induction therapy, mainly after block A. After the induction with R-m-NHL-BFM-90 8 out of 11 patients (72%) were iPET/CT-negative and received 2 additional courses of R-EPOCH; 3 out of 11 patients (28%) were iPET/CT-positive and received 4 additional courses of R-EPOCH. Only 1 patient`s response was assessed as DS4 at the end-of-treatment PET/CT. She received autologous transplantation of hematopoietic stem cells and has now been in complete remission for 12 months. With a median follow-up of 10 months (range 1-29) all the patients are alive in complete remission.

Conclusions: Despite a small number of patients and a short follow-up period, our results suggest that the response-adapted strategy of treatment is a reasonable option for PML patients, even in high risk of treatment failure.