Salvage Regimens With Autologous Transplantation for Relapsed Large B-Cell Lymphoma in the Rituximab Era

Abstract

Purpose Salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT) is the standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL). Salvage regimens have never been compared; their efficacy in the rituximab era is unknown. Patients and Methods Patients with CD20+ DLBCL in first relapse or who were refractory after first-line therapy were randomly assigned to either rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) or rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP). Responding patients received high-dose chemotherapy and ASCT. Results The median age of the 396 patients enrolled (R-ICE, n = 202; R-DHAP, n = 194) was 55 years. Similar response rates were observed after three cycles of R-ICE (63.5%; 95% CI, 56% to 70%) and R-DHAP (62.8%; 95 CI, 55% to 69%). Factors affecting response rates (P < .001) were refractory disease/relapse less than versus more than 12 months after diagnosis (46% v 88%, respectively), International Prognostic Index (IPI) of more than 1 versus 0 to 1 (52% v 71%, respectively), and prior rituximab treatment versus no prior rituximab (51% v 83%, respectively). There was no significant difference between R-ICE and R-DHAP for 3-year event-free survival (EFS) or overall survival. Three-year EFS was affected by prior rituximab treatment versus no rituximab (21% v 47%, respectively), relapse less than versus more than 12 months after diagnosis (20% v 45%, respectively), and IPI of 2 to 3 versus 0 to 1 (18% v 40%, respectively). In the Cox model, these parameters were significant (P < .001). Conclusion In patients who experience relapse more than 12 months after diagnosis, prior rituximab treatment does not affect EFS. Patients with early relapses after rituximab-containing first-line therapy have a poor prognosis, with no difference between the effects of R-ICE and R-DHAP.

Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial

“…24 Ifosfamide, etoposide, and cytarabine, contained in the consolidation, are the most common drugs used in salvage regimens after relapse subsequent to anthracycline-based treatment. 7 Outcome data in our patients treated with standard R-CHOP are consistent with our initial hypothesis The profi le of toxic eff ects for the R-ACVBP regimen is well characterised. The induction phase is associated with noticeable haematological toxic eff ects, which is why the regimen is only used in patients younger than 60 years.…”

“…In cases where the disease is refractory to immuno chemotherapy, the esti mate of progression-free survival at 3 years is only 23%, even with subsequent high-dose chemotherapy and autologous stem-cell trans plantation. 7 This situation empha sises the importance of fi rst-line treatment when crucial issues are still unresolved, such as establishing the optimum rituximab dose and schedule as well as the opti mum chemotherapy regimen to combine with rituximab.…”

Modified Irinotecan Plus Cisplatin and Dexamethasone (ICD) Combination Chemotherapy as Salvage Chemotherapy for Patients with Relapsed/Refractory Diffuse Large Cell Lymphoma

“…Overall response rate in our study for all the patients was 81 % but it was 90 % for the subgroup of patients treated as first salvage chemotherapy. Overall response rate of 90 % is acceptable and it is comparable with the results reported for ICE or DHAP protocols [2,[7][8][9]. This overall response rate is higher than original ICD (70 %) and this may be due to use of G-CSF that allowed us to administrate the planed dose of chemotherapy and complete the treatment protocol.…”

“…This group of the patients needs to be treated with salvage chemotherapy plus autologous stem cell transplantation but optimal salvage regimen is already unclear [2,3]. Kang et al [4] evaluated ICD (irinotecan, cisplatin and dexamethasone) regimen as salvage chemotherapy on 15 patients with relapsed or refractory lymphoma.…”

Monotherapy with pixantrone in histologically confirmed relapsed or refractory aggressive B‐cell non‐Hodgkin lymphoma: post‐hoc analyses from a phase III trial

“…The rate of CR or CRu in the pixantrone group was almost double that of comparator in the patients with prior rituximab treatment (20·0% vs. 11·5% in patients receiving pixantrone at any line of treatment), demonstrating the validity of pixantrone as a salvage treatment. The observation of efficacy in patients previously treated with rituximab is noteworthy, given that in many other studies, receipt of prior rituximab therapy substantially decreased the response rate to salvage therapies (Gisselbrecht et al , 2010). There was a non‐statistically significant trend towards improved OS in patients treated with pixantrone that appeared to be influenced by the number of prior regimens.…”