Early Response Evaluation with 18FDG-PET Scanning, but Not Phenotypic Profile, Are Predictive of Outcome in Diffuse Large B-Cell Lymphoma.
Authors: Dupuis Jehan , Gaulard Philippe , Itti Emmanuel , Rahmouni Alain , Hemery François , Brière Josette , Fabiani Bettina , Copie-Bergman Christiane , Gisselbrecht Christian , Meignan Michel , Reyes Félix , Haioun Corinne 
Published: October 2019

Abstract
Diffuse large B-cell lymphomas (DLBCLs) are heterogeneous in clinical presentation, histopathological and biological findings, and outcome. Today, risk-adapted treatment decisions are mainly based on the International Prognostic Index (IPI). Recently, molecular profiling has been shown to correlate with survival in DLBCL patients treated with conventional chemotherapy. Immunohistochemistry (IHC) has been proposed as a surrogate of molecular profiling (« phenotypic profiling»). Besides, we and others have shown that early response evaluation (after 2 cycles) with 18FDG-PET scanning is predictive of patient outcome in DLBCL, independently of IPI (Haioun & al, Blood2005; 106: 1376). We retrospectively investigated the phenotypic profile of 81 patients (pts) from our recently published series with a confirmed diagnosis of DLBCL and available material for extensive IHC analyses. Diagnosis was based on a nodal (n=45), extranodal (n=25) or mediastinal (n=11) specimen. IHC was performed with the markers bcl2, CD10, bcl6 and MUM1, and scored by two observers. Pts were classified as having a germinal center (GC) or non germinal center (nGC) profile using the following algorithm: GC pts were to be CD10+ or bcl6+ and MUM1−, and all others were nGC (Hans & al, Blood2004; 103: 275). Bcl2 was positive in 53%, CD10 in 36%, bcl6 in 58% and MUM1 in 45% of interpretable cases. Seventy-four pts (91%) had an interpretable profile, 39 (52%) were in the GC group, 35 (48%) in the nGC group. All pts received a doxorubicin-containing regimen as induction treatment, with rituximab for 46% of them. Pretreatment characteristics and early response by 18FDG-PET according to phenotypic profile are shown in the table below. With a median follow-up of 33 months, estimated 2-y OS and EFS were 75% and 67%. Survival analysis confirmed the poor prognostic value of a positive early 18FDG-PET scan: 2-y EFS was 46% in the PET-positive group and 80% in the PET-negative group (p = 0.0003). Two-year EFS was 61% and 73% in the bcl2-positive and negative groups, respectively (p = 0.08). We could not observe any prognostic influence of the GC vs nGC profile: Two-year EFS was 72% in the GC and 64% in the nGC group (p=0.62). In this limited series, we confirm the high predictive value of early response evaluation with 18FDG-PET scanning, but did not observe any significative influence of phenotypic profile, contrarily to several published reports. The reasons for this discrepancy, be they related to treatment type (including rituximab), disease presentation (many pts with extranodal disease) or IHC evaluation (fixation, scoring), remain to be understood. Meanwhile, 18FDG-PET should be an early guide for first-line strategies in DLBCL.
Characteristics according to phenotypic profile GC (n=39) nGC (n=35) p Age <= 60 74 % 78 % 0.68 IPI Int-Hi/Hi 65 % 54 % 0.71 Bone marrow involvement 17 % 39 % 0.03 Biopsy territory Nodal/Extranodal/Mediastinal 50/36/14 % 54/31/15 % 0.56 18FDG-PET positive after 2 cycles 34 % 39 % 0.77 bcl2 positive 50 % 52 0.92