FDG-PET–driven consolidation strategy in diffuse large B-cell lymphoma: final results of a randomized phase 2 study

Abstract

Key Points• Superiority of R-ACVBP over R-CHOP14 was not established, as IHP criteria driving consolidation did not properly reflect disease control.• The 26% PET2 2 /PET4 2 patients using IHP criteria increased to 79% using DSUVmax, which may help better select those needing an alternative to SIC.Dose-dense induction and up-front consolidation with autologous stem cell transplantation (ASCT) remain controversial issues when treating patients with high-risk diffuse large B-cell lymphoma. GELA designed a randomized phase 2 trial evaluating the efficacy of either rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone (R-ACVBP) or rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP14) induction and a positron emission tomography (PET)-driven ASCT or standard immunochemotherapy (SIC) consolidation in age-adjusted international prognosis index 2 (aaIPI2)-aaIPI3 patients. PET was performed at baseline, after 2 (PET2) and 4 (PET4) induction cycles, and centrally assessed using international harmonization project (IHP) criteria. PET2 2 / PET4 2 patients were assigned SIC, PET2 1 /PET4 2 patients were assigned ASCT, and PET4 1 patients were treated with the investigator's choice. The primary end-point was the 2007 international working group complete response (CR) rate after induction. Change in maximum standard uptake value (DSUVmax) after PET assessment was explored. Two hundred eleven patients were randomly assigned to R-ACVBP (n 5 109) or R-CHOP14 (n 5 102). PET4 2 /CR rates were 53%/47% with R-ACVBP and 41%/39% with R-CHOP14 (CR 95% confidence interval [CI], 38%-67% and 28%-54%, respectively; P 5 .076). Consolidation in the R-ACVBP and R-CHOP14 groups was SIC in 26% and 23% of patients and ASCT in 28% and 18% of patients, respectively. PET4 positivity was higher with R-CHOP14 vs R-ACVBP (54% vs 41%; P 5 .08), leading to more salvage therapy (37% vs 26%; P 5 .07) and lower event-free survival (EFS; 4-year EFS, 31% vs 43%; P < .01), but progression-free survival (PFS) and overall survival (OS) were similar in both groups. PET2 2 /PET42 and PET2 1 /PET4 2 patients had similar outcomes. Using DSUVmax, 79% of the patients were PET2 2 /PET4 2 . DSUVmaxPET0-4 >70% was associated with better outcome (4-year PFS, 84% vs 35%; 4-year OS, 91% vs 57%; P < .0001), whatever the consolidation. Superiority of R-ACVBP over R-CHOP14 was not established, as IHP criteria did not properly reflect disease control. DSUVmax may help better select patients needing an alternative to SIC, including ASCT. (Blood. 2017;130(11):1315-1326

FDG-PET Imaging for Hodgkin and Diffuse Large B-Cell Lymphoma—An Updated Overview

“…Non-responders underwent salvage treatment according to local investigators. Based on the exploratory results of the LNH2007-3B study [51], PET positivity was defined as a decline of SUV max in an FDG-avid target lesion of at least 66% or 70% from baseline to PET after 2 and 4 cycles of chemotherapy, respectively. This trial aimed to validate the ∆SUV max -driven consolidation in young patients with high-risk disease.…”

FDG‐PET/CT in the management of lymphomas: current status and future directions

“…Interim PET has been evaluated as a possible biomarker of early R‐CHOP success or failure in several retrospective and prospective studies. About 39–87% patients achieve a negative interim FDG‐PET/CT in prospective studies of advanced stage DLBCL initially receiving R‐CHOP, as shown in Table . The rate of interim FDG‐PET/CT negativity is very broad due to significant heterogeneity between studies, including variable timing of the interim PET (after 2, 3, or 4 cycles) as well as variable interpretation criteria with different definitions of FDG‐PET/CT positivity (internal visual point systems, International Harmonization Project criteria, Deauville criteria).…”

High-risk DLBCL: interim PET? Not yet

“…Using an interim positron emission tomography (PET)-adapted approach to consolidation therapy, they show that quantitative rather than qualitative PET assessment may better select some patients needing alternative treatments, including autologous stem cell transplantation (ASCT). 1 …”

“…1 In recent years, gene therapy for blood cell diseases in which autologous hematopoietic stem cells (HSCs) are corrected using a lentiviral vector has led to clinical benefits similar to those from allogeneic transplant. Much of the focus has been on severe diseases affecting infants and young children (severe combined immunodeficiency, X-linked adrenoleukodystrophy, metachromatic leukodystrophy) in which early intervention has the potential to prevent the…”