Identification of a patient cohort with relapsing diffuse large b-cell lymphoma with a low international prognostic index in pet/ct using a 2-gene (lmo2/tnfrsf9) scoring system

Abstract

Treating patients with diffuse large Bcell lymphoma (DLBCL) remains a challenge, with a remission rate of 75% at 2 years from diagnosis. The International Prognostic Index (IPI) [1] and molecularcharacterization [2] are employed in the stratification and relapse prediction. Additionally, 18F-fluorodeoxyglucose positron emission tomography (PET) and computed tomography (CT) have now become part of standard care in differentiating metabolic activity of the disease from fibrosisor necrosis [3]. Early optimism that the speed of response to treatment, as indicated by an interim-PET (iPET) scan after 2?3 cycles of chemotherapy, might reliably predict cure has not been fulfilled [4].To investigate the role of both an interim and an end-treatment-PET (ePET) scan for the management of DLBCL in an international setting, at a time when PET centers were becoming established globally, the International Atomic Energy Agency (IAEA) sponsored a study across 7 countries in Europe, South Asia, Southeast Asia, and South America [5]. This study, the largest study to date, found that 34% of cases were iPET+ after 2 or 3 cycles of standard chemotherapy (R-CHOP), but 54% of the iPET+ cases became ePET?; and that these ?slow responders? had relatively good outcomes at 2 years (event-free survival, EFS: 86%). Notably, the study found that by combining a negative iPET scan with 2 clinical components of the IPI (normal LDH and good performance status), it was possible to identify a population, 35% of all cases, 98% of whom were disease free 2 years after diagnosis. By contrast, iPET+ cases that remained PET+ at the end of treatment had dismal outcomes. These findings raisethe important question of how to separate slow-responding iPET+ cases who are PET? at the end treatment, who are destined for good survival, from those who will fail to achieve a complete or stable remission by continuing standard therapy.