Early Treatment Intensification With R-ICE And 90Y-Ibritumomab Tiuxetan (Zevalin)-BEAM Stem Cell Transplantation In Patients With High Risk Diffuse Large B-Cell Lymphoma Patients And Positive Interim PET After 4 Cycles Of R-CHOP-14

In the treatment of diffuse large B-cell lymphoma a persistently positive [18F]fluorodeoxyglucose positron emission tomography (PET) scan typically carries a poor prognosis. In this prospective multi-center phase 2 study, we sought to establish whether treatment intensification with R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) chemotherapy followed by 90Y-ibritumomab tiuxetan-BEAM (BCNU, etoposide, cytarabine, and melphalan) for high risk diffuse large B-cell lymphoma patients who are positive on interim PET scan after 4 cycles of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, and prednisone), can improve 2-year progression-free survival from an historically unfavourable rate of 40% to a rate of 65%. Patients received 4 cycles of R-CHOP-14, followed by a centrally-reviewed PET performed at day 17 to 20 of cycle 4 and assessed according to International Harmonisation Project criteria. Median age of the 151 evaluable patients was 57 years with 79% stages 3-4, 54% bulk, and 54% International Prognostic Index 3-5. Among the 143 patients undergoing interim PET, 101 (71%) were PET-negative, 96 of whom completed R-CHOP; 42 (29%) were PET-positive, 32 of whom completed R-ICE and 90Y-ibritumomab tiuxetan-BEAM. At a median follow-up of 35 months, the 2-year progression free survival for PET-positive patients was 67%, a rate similar to that for PET-negative patients treated with R-CHOP-14 (74%, P=0.11); overall survival was 78% and 88% (P=0.11), respectively. In an exploratory analysis, progression free and overall survival were markedly superior for PET-positive Deauville score 4 versus score 5 (P=0.0002 and P=0.001). Hence, diffuse large B-cell lymphoma patients who are PET-positive after 4 cycles of R-CHOP-14 and switched to R-ICE and 90Y-ibritumomab tiuxetan-BEAM achieve favourable survival outcomes similar to that for PET-negative R-CHOP-14-treated patients. Further studies are warranted to confirm these promising results. (ACTRN12609001077257)