Haema 2017; 8(1): 39-53
by Theodoros P. Vassilakopoulos, Kiriaki Petevi, Μaria K. Αngelopoulou
Department of Hematology and Bone Marrow Transplantation, Medical School, National and Kapodistrian University of Athens, “Laikon” General Hospital, Athens, Greece
Abstract
Primary mediastinal large B-cell lymphoma (PMLBCL) represents a separate disease entity among aggressive B-cell lymphomas, accounting for 2.5% of all non-Hodgkin’s lymphomas. The disease bears distinctive demographic (younger age female predominance), clinical, histologic, immunohistochemical and molecular findings. The molecular signature of PMLBCL rather resembles to classical Hodgkin lymphoma than to diffuse large B-cell lymphoma, including the constitutive activation of NFκΒ and the JAK-STAT pathway, as well as the overexpression of PDL-1 and PDL-2. The latter may have obvious therapeutic implications. Immunochemotherapy with standard R-CHOP-21 still remains the “gold standard” against which more intensive approaches should be compared. Indeed, R-CHOP- 21±radiotherapy (RT) may produce durable complete remission in 75% and long-term survival in 85- 90% of unselected patients. R-DA-EPOCH without RT has produced considerably better results in rather small phase II studies, but its superiority over R-CHOP has not been tested in randomized trials. Furthermore, the magnitude of the potential superiority of R-DA-EPOCH over R-CHOP is not well established. The satisfactory results obtained with R-CHOP and the rarity of PMLBCL do not easily permit the emergence of formal evidence for the superiority of R-DA-EPOCH. This might require the recognition of reliable and reproducible prognostic factors, in order to focus any comparison to higher-risk patients. However, a more realistic application of R-DA-EPOCH in PMLBCL could target the omission of RT without any loss in efficacy, which still remains uncertain with R-CHOP. The selection of patients for complementary RT after R-CHOP is currently made on empirical grounds, while the role of PET in this decision-making process is still emerging, but will be more accurately defined by the ongoing IELSG-37 randomized trial. Primary treatment failure is due to primary refractory or very rapidly relapsing disease in the vast majority of cases. The standard of care for these patients is salvage chemoimmunotherapy followed by autologous stem cell transplantation (ASCT), in case of chemosensitivity. PD-1 inhibitors appear to be promising in heavily pretreated patients, in which the disease is expected to be rapidly lethal. Thus, this class of novel agents might improve survival in heavily pretreated patients who fail ASCT or are not candidates for the procedure or even improve the efficacy of 1st or 2nd line therapy, which should be tested in future trials.