Interim Restaging FDG-PET/CT to Guide Use of High Dose Sequential Induction Therapy with Rituximab-Dose-Intensive Cyclophosphamide, Etoposide, Cisplatin (RDICEP) and Rituximab-Carmustine, Etoposide, Cytarabine, Melphalan (RBEAM) and Autologous Stem Cell Transplantation (ASCT) for Poor Prognosis Diffuse Large B-Cell Lymphoma (DLBCL). ClinicalTrials. Gov Identifier: NCT00530179.

Approximately 50-55% of patients (pts) with stage 3-4 DLBCL and elevated serum LDH achieve long-term event-free survival (EFS) following R-CHOP chemotherapy. A prospective, multicentre, phase II clinical trial was designed to evaluate the use of high dose sequential therapy with RDICEP then RBEAM/ASCT for such pts who have positive interim restaging FDG-PET/CT scans after 2 cycles of RCHOP.

Pts were eligible if they were HIV-, 18-65 years of age, and had stage 3-4 DLBCL with elevated serum LDH. An FDG-PET/CT scan was performed 10-15 days following the second cycle of R-CHOP. Pts with negative interim restaging PET scans completed 4 further cycles of RCHOP, whereas pts with positive PET scans (more than 1 site with uptake more intense than background liver) received one cycle of RDICEP (Rituximab 375mg/m² day 1 and 8, C 1.75g/m² d2-4, E 350mg/m² d2-4 P 35mg/m² d2-4, G-CSF d15-21 and autologous blood stem cell collection by apheresis d21or 22) followed by one cycle of RBEAM/ASCT (Rituximab 375mg/m² day -6 and +14, BCNU 300mg/m² d-6, E 200mg/m² d-5to-2, A 400mg/m² d-5to-2, M 140mg/m² d-1).

Of the 36 pts who have been accrued from 5/2007-7/2009, 33 pts have undergone interim PET/CT restaging following 2 cycles RCHOP. All 33 pts had IPI scores 3-5, the median age was 55 years (range19-65) with 7 pts (21%) older than 60 years, 20 (61%) had ECOG status 2-4, 28 (85%) had stage 4, 22 (67%) >1 extranodal site. At a median follow-up of 12mo, the 1 year OS and EFS rates for all 33 pts are 82% (95%CI = 66-98%) and 76% (95%CI = 58-83%), respectively. Interim restaging PET/CT was positive for 16 pts and negative for 17 pts. The EFS rates for PET+ and PET- pts are 78% (95%CI = 57-100%) and 66% (95%CI = 36-99%), respectively (logrank p=0.97). To date, 4 pts have died, 3 from lymphoma at 6, 10, 11 months post-RCHOP1, and 1 from sepsis and necrotic bowel on day 5 post-ASCT.

Preliminary results of this phase II study are encouraging, and suggest that high dose induction therapy with RDICEP and RBEAM/ASCT might improve EFS for poor prognosis DLBCL with positive interim restaging PET/CT. Accrual will continue to target ≥ 35 PET+ and ≥35 PET- pts.

Stewart:Hoffmann La Roche: Advisory Board, Honoraria, Research Funding. Off Label Use: Rituximab with High Dose Chemotherapy and Autologous Stem Cell Transplantation for DLBCL. Bence-Bruckler:Hoffmann La Roche: Honoraria, Research Funding.