High dose chemotherapy (HDT) with autologous stem cell support (ASCT) has been proven effective in relapsed/refractory DLBCL, who are sensitive to salvage chemotherapy. The salvage regimen IDEA was previously reported as effective (ORR; 67.6%) and feasible to mobilize PBSCs (77.8%). (Nishimori et al. Antican Res 2009) The interim analysis of this phase II trial addressing safety and efficacy was presented in ESMO 2014. Herein, we report final results of the survival analysis.
This study includes pts aged 18-65 years with primary refractory or first relapse CD20+ DLBCL after R-CHOP. The R-IDEA regimen consisits of R 375mg/m2 on day 1, IFO 1.3g/m2, ETP 150mg/m2 on days 2-4, Dex 33mg IV on days 2-5 and Ara-C 750mg/m2 twice daily on days 3-4. R-IDEA was administered every 21 days for a total of 3 cycles. PBSCs were harvested after cycle 3. HDT regimen was based on institutional preference. Primary endpoint was mobilization adjusted response rate (MARR; [CR] + [PR] - mobilization failure). Secondary endpoints included 2-year overall survival (OS), 2-year progression-free survival (PFS), transplanted rate, mobilization efficiency and toxicity.
20 pts were enrolled (median age 59.5, range 42-65; M:F ratio 11:9). 17 pts were enrolled after first relapse and three were refractory to first line chemotherapy. Five pts relapsed within 1 year after diagnosis. The most frequent grade 3/4 adverse events were neutropenia, thrombocytopenia, anemia and febrile neutropenia. After completion of R-IDEA chemotherapy, seven pts achieved CR, five PR, one had SD, seven had PD. The median CD34+ cell count was 2.6 million/kg (0.17-43.7) and median number of apheresis days was two. In 12 sensitive relapsed pts, two failed to mobilization, for a MARR of 50% (10/20). No patient of primary refractory or relapsed within 1 year after diagnosis achieved MARR. In total, 12 pts (10 pts with MARR, 1pt in SD and 1 pt in CR with CD34+ 1.5million/kg) received HDT/ASCT. The OS and PFS at two years was 38.5% and 29.2%, respectively.
As previously reported in PARMA study and CORAL study, primary refractory and early relapsed DLBCL pts had an extremely poor prognosis. New treatment strategy seems to be warranted for the high risk pts.
Clinical trial identification
UMIN000004892 (release date: 20 Jan, 2011)
Legal entity responsible for the study
The society of lymphoma treatment in Japan
The society of lymphoma treatment in Japan (SoLT-J) and the west japan hematology/oncology group (WestJHOG)
All authors have declared no conflicts of interest.