Independent Predictive Value of PET-CT Pre Transplant in Relapsed and Refractory Patients with CD20 Diffuse Large B-Cell Lymphoma (DLBCL) Included in the CORAL Study.

DLBCL CD 20+ in first relapse or pts refractory after first line therapy were randomized between R-DHAP and R-ICE. Response was evaluated according to Cheson Criteria (1999); chemosensitive patients after 3 cycles received BEAM and ASCT, and were randomized between observation and maintenance with rituximab for 1 yr. PET scan was not required at the time of design of the study but recommended, whenever possible. Consequently, the assessment of response with PET scan was also performed in a subset of patients and could be compared to revised Cheson criteria (2007).

Intent to treat analysis was made on 394 pts ( 201 R ICE arm, 193 R DHAP arm) and was reported earlier this year (J Clin Oncol 27:15s, 2009 (suppl; abstr 8509). There was no difference between the two treatments arms. Prospectively, 123 pts with PET scans were recorded at the end of induction treatment and were reported by investigators positive or negative. Functional imaging was not used to modify treatment protocol. PET was negative ( FDG non-avid) in 61 pts and positive ( FDG-avid) in 62 pts; 60 and 58 pts completed 3 cycles of R-ICE or R-DHAP; 50 PET-ve and 26 PET +ve pts received BEAM respectively. Median age 54 yrs.; 52 relapses >12 months, 71 refractory/early relapses <12 months; 77 pts had prior exposure to rituximab; secondary IPI 0-1 77 pts, sIPI 2-3 40 pts. The overall response rate was 74%, with 47% complete remission. The number of CR, CRu, PR were 42,11,7 in PET negative pts and 1,4,26 in PET positive pts respectively. There was a highly significant difference (p<0.0001) in response rate per CT for PET negative 98% (CI 91-100%) vs. PET positive 50% (CI 37-63%) patients. Thus using updated criteria with PET, all the patients negative, except one stable, should be now characterized as complete responders. Whereas, only 5 pts PET positive were recorded to be in CR or CRu. No histology was available. For the whole population, three years EFS was 30%. EFS were different in pet negative pts 40% vs. 16% for positive pts ( p<0.0001). The same significant difference was found for PFS 43% vs. 28% respectively. Three years overall survival was 47%, for pts PET-ve 66% vs. pts PET+ve 49% ( p=0.007). For the 26 patients submitted to transplantation with PET positivity there was a significant difference for EFS (p=0.03) when compared to PET negative patients, but no statistical difference in PFS and OS. Factors affecting response rate in multivariate analysis were early relapse/refractory < 12 months and PET+ve following induction. The same factors were found in cox's model for EFS and PFS.

This prospective study in relapsing DLBCL shows that PET scan is accurate to predict outcome. PET is an independent predictive factor with early relapse/refractory <12 months. A PET positivity pretransplantation is associated with a poor outcome and argues for new therapeutic approaches in this population.

No relevant conflicts of interest to declare.