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

Abstract

I n the treatment of diffuse large B-cell lymphoma, a persistently positive [ 18 F]fluorodeoxyglucose positron emission tomography (PET) scan typically carries a poor prognosis. In this prospective multi-center phase II 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 a historically unfavorable 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 17-20 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 PETpositive (32 of whom completed R-ICE and 90Y-ibritumomab tiuxetan-BEAM). At a median follow up of 35 months, the 2-year progressionfree survival for PET-positive patients was 67%, a rate similar to that for

Interim PET-driven strategy in de novo diffuse large B-cell lymphoma: do we trust the driver?

“…In an exploratory analysis, the PFS and OS were markedly superior for iPET4-positive patients with a score of 4 on the 5-PS vs those with a score of 5 (P 5 .0002, and P 5 .001). 31 The phase 3 PETAL trial (NCT00554164) (n 5 853) randomized patients to either a standard R-CHOP14 treatment or an escalated therapy using a Burkitt-type regimen for patients with a DSUVmax , 66% after 2 cycles of R-CHOP14. 32 In this study, as in the LYSA study, there was rigorous scanner quality control and standardized conditions for PET acquisition and interpretation.…”

Prognostic utility of pre‐transplantation [18F] fluorodeoxyglucose positron emission tomography/computed tomography in patients with diffuse large B‐cell lymphoma who underwent rituximab, dexamethasone, high‐dose cytarabine, carboplatin salvage chemotherapy

“…A role for [ 18 F] fluorodeoxyglucose (FDG)‐positron emission tomography/computed tomography (FDG‐PET/CT) in the prediction and evaluation of tumour responses to ASCT has been recognised in a few studies; but interpretation of FDG‐PET has not been standardised (Derenzini et al , ; Dickinson et al , ; Armand et al , ; Hertzberg et al , ). More recently, studies analysed the prognostic utility of PET prior to ASCT using the Deauville criteria (Sauter et al , ; Hertzberg et al , ; Winter et al , ). However, most patients had received ICE salvage chemotherapy (Sauter et al , ; Hertzberg et al , ).…”

“…More recently, studies analysed the prognostic utility of PET prior to ASCT using the Deauville criteria (Sauter et al , ; Hertzberg et al , ; Winter et al , ). However, most patients had received ICE salvage chemotherapy (Sauter et al , ; Hertzberg et al , ). Hence, the prognostic utility of PET/CT in patients treated with the R‐DHAC salvage regimen prior to high dose therapy (HDT)‐ASCT remains unclear.…”

The role of autologous stem cell transplantation in diffuse large B‐cell lymphoma

“…Interim positive PET was observed in 42 of 143 patients (29%), and 32 of these patients underwent intensification treatment and stem cell transplantation. The 2‐year PFS for PET‐positive patients was 67%, a similar rate to PET‐negative patients treated with RCHOP‐14 alone (74%), and OS of 78% for the intensification group as compared to PET‐negative patients treated with chemotherapy only (OS 88%) with no significant difference . While these data appear promising, further studies are needed to determine the benefit of intensification therapy and stem cell transplantation based on interim PET scan in DLBCL.…”