Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era

Christian Gisselbrecht, Bertram Glass, Nicolas Mounier, Devinder Singh Gill, David C. Linch, Marek Trneny, Andre Bosly, Nicolas Ketterer, Ofer Shpilberg, Hans Hagberg, David Ma, Josette Brière, Craig Moskowitz, Norbert Schmitz

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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.

Original languageEnglish (US)
Pages (from-to)4184-4190
Number of pages7
JournalJournal of Clinical Oncology
Volume28
Issue number27
DOIs
StatePublished - Sep 20 2010
Externally publishedYes

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Autologous Transplantation
B-Cell Lymphoma
Recurrence
Disease-Free Survival
Lymphoma, Large B-Cell, Diffuse
Stem Cell Transplantation
Therapeutics
Rituximab
Drug Therapy
Ifosfamide
Carboplatin
Cytarabine
Etoposide
Proportional Hazards Models
Dexamethasone
Cisplatin
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Gisselbrecht, C., Glass, B., Mounier, N., Gill, D. S., Linch, D. C., Trneny, M., ... Schmitz, N. (2010). Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. Journal of Clinical Oncology, 28(27), 4184-4190. https://doi.org/10.1200/JCO.2010.28.1618

Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. / Gisselbrecht, Christian; Glass, Bertram; Mounier, Nicolas; Gill, Devinder Singh; Linch, David C.; Trneny, Marek; Bosly, Andre; Ketterer, Nicolas; Shpilberg, Ofer; Hagberg, Hans; Ma, David; Brière, Josette; Moskowitz, Craig; Schmitz, Norbert.

In: Journal of Clinical Oncology, Vol. 28, No. 27, 20.09.2010, p. 4184-4190.

Research output: Contribution to journalArticle

Gisselbrecht, C, Glass, B, Mounier, N, Gill, DS, Linch, DC, Trneny, M, Bosly, A, Ketterer, N, Shpilberg, O, Hagberg, H, Ma, D, Brière, J, Moskowitz, C & Schmitz, N 2010, 'Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era', Journal of Clinical Oncology, vol. 28, no. 27, pp. 4184-4190. https://doi.org/10.1200/JCO.2010.28.1618
Gisselbrecht, Christian ; Glass, Bertram ; Mounier, Nicolas ; Gill, Devinder Singh ; Linch, David C. ; Trneny, Marek ; Bosly, Andre ; Ketterer, Nicolas ; Shpilberg, Ofer ; Hagberg, Hans ; Ma, David ; Brière, Josette ; Moskowitz, Craig ; Schmitz, Norbert. / Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 27. pp. 4184-4190.
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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.",
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AU - Gisselbrecht, Christian

AU - Glass, Bertram

AU - Mounier, Nicolas

AU - Gill, Devinder Singh

AU - Linch, David C.

AU - Trneny, Marek

AU - Bosly, Andre

AU - Ketterer, Nicolas

AU - Shpilberg, Ofer

AU - Hagberg, Hans

AU - Ma, David

AU - Brière, Josette

AU - Moskowitz, Craig

AU - Schmitz, Norbert

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N2 - 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.

AB - 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.

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