Final Results of the IELSG-19 Randomized Trial of Mucosa-Associated Lymphoid Tissue Lymphoma: Improved Event-Free and Progression-Free Survival With Rituximab Plus Chlorambucil Versus Either Chlorambucil or Rituximab Monotherapy

Emanuele Zucca, Annarita Conconi, G Martinelli, R Bouabdallah, Alessandra Tucci, Umberto Vitolo, M Martelli, R Pettengell, Gilles Salles, C Sebban, AL Guillermo, Graziella Pinotti, L Devizzi, F Morschhauser, H Tilly, V Torri, S Hohaus, AJM Ferreri, P Zachée, A BoslyC Haioun, C Stelitano, M Bellei, M Ponzoni, A Moreau, A Jack, E Campo, L Mazzucchelli, Franco Cavalli, P Johnson, C Thieblemont

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Abstract

There is no consensus on the optimal systemic treatment of patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The IELSG-19 phase III study, to our knowledge, was the first such study to address the question of first-line treatment in a randomized trial. Patients and Methods Eligible patients were initially randomly assigned (1:1 ratio) to receive either chlorambucil monotherapy (6 mg/m2/d orally on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18, and 21 to 22) or a combination of chlorambucil (same schedule as above) and rituximab (375 mg/m2 intravenously on day 1 of weeks 1, 2, 3, 4, 9, 13, 17, and 21). After the planned enrollment of 252 patients, the protocol was amended to continue with a three-arm design (1:1:6 ratio), with a new arm that included rituximab alone (same schedule as the combination arm) and with a final sample size of 454 patients. The main end point was event-free survival (EFS). Analysis of chlorambucil versus the combination arm was performed and reported separately before any analysis of the third arm. Results At a median follow-up of 7.4 years, addition of rituximab to chlorambucil led to significantly better EFS (hazard ratio, 0.54; 95% CI, 0.38 to 0.77). EFS at 5 years was 51% (95% CI, 42 to 60) with chlorambucil alone, 50% (95% CI, 42 to 59) with rituximab alone, and 68% (95% CI, 60 to 76) with the combination ( P = .0009). Progression-free survival was also significantly better with the combination ( P = .0119). Five-year overall survival was approximately 90% in each arm. All treatments were well tolerated. No unexpected toxicities were recorded. Conclusion Rituximab in combination with chlorambucil demonstrated superior efficacy in mucosa-associated lymphoid tissue lymphoma; however, improvements in EFS and progression-free survival did not translate into longer overall survival.
Original languageEnglish
Pages (from-to)1905-1912
Number of pages8
JournalJournal of Clinical Oncology
Volume35
Issue number17
DOIs
Publication statusPublished - 2017

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Chlorambucil
Marginal Zone B-Cell Lymphoma
Disease-Free Survival
Appointments and Schedules
Survival
Sample Size
Rituximab
Therapeutics

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Final Results of the IELSG-19 Randomized Trial of Mucosa-Associated Lymphoid Tissue Lymphoma: Improved Event-Free and Progression-Free Survival With Rituximab Plus Chlorambucil Versus Either Chlorambucil or Rituximab Monotherapy. / Zucca, Emanuele; Conconi, Annarita; Martinelli, G; Bouabdallah, R; Tucci, Alessandra; Vitolo, Umberto; Martelli, M; Pettengell, R; Salles, Gilles; Sebban, C; Guillermo, AL; Pinotti, Graziella; Devizzi, L; Morschhauser, F; Tilly, H; Torri, V; Hohaus, S; Ferreri, AJM; Zachée, P; Bosly, A; Haioun, C; Stelitano, C; Bellei, M; Ponzoni, M; Moreau, A; Jack, A; Campo, E; Mazzucchelli, L; Cavalli, Franco; Johnson, P; Thieblemont, C.

In: Journal of Clinical Oncology, Vol. 35, No. 17, 2017, p. 1905-1912.

Research output: Contribution to journalArticle

Zucca, E, Conconi, A, Martinelli, G, Bouabdallah, R, Tucci, A, Vitolo, U, Martelli, M, Pettengell, R, Salles, G, Sebban, C, Guillermo, AL, Pinotti, G, Devizzi, L, Morschhauser, F, Tilly, H, Torri, V, Hohaus, S, Ferreri, AJM, Zachée, P, Bosly, A, Haioun, C, Stelitano, C, Bellei, M, Ponzoni, M, Moreau, A, Jack, A, Campo, E, Mazzucchelli, L, Cavalli, F, Johnson, P & Thieblemont, C 2017, 'Final Results of the IELSG-19 Randomized Trial of Mucosa-Associated Lymphoid Tissue Lymphoma: Improved Event-Free and Progression-Free Survival With Rituximab Plus Chlorambucil Versus Either Chlorambucil or Rituximab Monotherapy', Journal of Clinical Oncology, vol. 35, no. 17, pp. 1905-1912. https://doi.org/10.1200/JCO.2016.70.6994
Zucca, Emanuele ; Conconi, Annarita ; Martinelli, G ; Bouabdallah, R ; Tucci, Alessandra ; Vitolo, Umberto ; Martelli, M ; Pettengell, R ; Salles, Gilles ; Sebban, C ; Guillermo, AL ; Pinotti, Graziella ; Devizzi, L ; Morschhauser, F ; Tilly, H ; Torri, V ; Hohaus, S ; Ferreri, AJM ; Zachée, P ; Bosly, A ; Haioun, C ; Stelitano, C ; Bellei, M ; Ponzoni, M ; Moreau, A ; Jack, A ; Campo, E ; Mazzucchelli, L ; Cavalli, Franco ; Johnson, P ; Thieblemont, C. / Final Results of the IELSG-19 Randomized Trial of Mucosa-Associated Lymphoid Tissue Lymphoma: Improved Event-Free and Progression-Free Survival With Rituximab Plus Chlorambucil Versus Either Chlorambucil or Rituximab Monotherapy. In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 17. pp. 1905-1912.
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title = "Final Results of the IELSG-19 Randomized Trial of Mucosa-Associated Lymphoid Tissue Lymphoma: Improved Event-Free and Progression-Free Survival With Rituximab Plus Chlorambucil Versus Either Chlorambucil or Rituximab Monotherapy",
abstract = "There is no consensus on the optimal systemic treatment of patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The IELSG-19 phase III study, to our knowledge, was the first such study to address the question of first-line treatment in a randomized trial. Patients and Methods Eligible patients were initially randomly assigned (1:1 ratio) to receive either chlorambucil monotherapy (6 mg/m2/d orally on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18, and 21 to 22) or a combination of chlorambucil (same schedule as above) and rituximab (375 mg/m2 intravenously on day 1 of weeks 1, 2, 3, 4, 9, 13, 17, and 21). After the planned enrollment of 252 patients, the protocol was amended to continue with a three-arm design (1:1:6 ratio), with a new arm that included rituximab alone (same schedule as the combination arm) and with a final sample size of 454 patients. The main end point was event-free survival (EFS). Analysis of chlorambucil versus the combination arm was performed and reported separately before any analysis of the third arm. Results At a median follow-up of 7.4 years, addition of rituximab to chlorambucil led to significantly better EFS (hazard ratio, 0.54; 95{\%} CI, 0.38 to 0.77). EFS at 5 years was 51{\%} (95{\%} CI, 42 to 60) with chlorambucil alone, 50{\%} (95{\%} CI, 42 to 59) with rituximab alone, and 68{\%} (95{\%} CI, 60 to 76) with the combination ( P = .0009). Progression-free survival was also significantly better with the combination ( P = .0119). Five-year overall survival was approximately 90{\%} in each arm. All treatments were well tolerated. No unexpected toxicities were recorded. Conclusion Rituximab in combination with chlorambucil demonstrated superior efficacy in mucosa-associated lymphoid tissue lymphoma; however, improvements in EFS and progression-free survival did not translate into longer overall survival.",
author = "Emanuele Zucca and Annarita Conconi and G Martinelli and R Bouabdallah and Alessandra Tucci and Umberto Vitolo and M Martelli and R Pettengell and Gilles Salles and C Sebban and AL Guillermo and Graziella Pinotti and L Devizzi and F Morschhauser and H Tilly and V Torri and S Hohaus and AJM Ferreri and P Zach{\'e}e and A Bosly and C Haioun and C Stelitano and M Bellei and M Ponzoni and A Moreau and A Jack and E Campo and L Mazzucchelli and Franco Cavalli and P Johnson and C Thieblemont",
year = "2017",
doi = "10.1200/JCO.2016.70.6994",
language = "English",
volume = "35",
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TY - JOUR

T1 - Final Results of the IELSG-19 Randomized Trial of Mucosa-Associated Lymphoid Tissue Lymphoma: Improved Event-Free and Progression-Free Survival With Rituximab Plus Chlorambucil Versus Either Chlorambucil or Rituximab Monotherapy

AU - Zucca, Emanuele

AU - Conconi, Annarita

AU - Martinelli, G

AU - Bouabdallah, R

AU - Tucci, Alessandra

AU - Vitolo, Umberto

AU - Martelli, M

AU - Pettengell, R

AU - Salles, Gilles

AU - Sebban, C

AU - Guillermo, AL

AU - Pinotti, Graziella

AU - Devizzi, L

AU - Morschhauser, F

AU - Tilly, H

AU - Torri, V

AU - Hohaus, S

AU - Ferreri, AJM

AU - Zachée, P

AU - Bosly, A

AU - Haioun, C

AU - Stelitano, C

AU - Bellei, M

AU - Ponzoni, M

AU - Moreau, A

AU - Jack, A

AU - Campo, E

AU - Mazzucchelli, L

AU - Cavalli, Franco

AU - Johnson, P

AU - Thieblemont, C

PY - 2017

Y1 - 2017

N2 - There is no consensus on the optimal systemic treatment of patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The IELSG-19 phase III study, to our knowledge, was the first such study to address the question of first-line treatment in a randomized trial. Patients and Methods Eligible patients were initially randomly assigned (1:1 ratio) to receive either chlorambucil monotherapy (6 mg/m2/d orally on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18, and 21 to 22) or a combination of chlorambucil (same schedule as above) and rituximab (375 mg/m2 intravenously on day 1 of weeks 1, 2, 3, 4, 9, 13, 17, and 21). After the planned enrollment of 252 patients, the protocol was amended to continue with a three-arm design (1:1:6 ratio), with a new arm that included rituximab alone (same schedule as the combination arm) and with a final sample size of 454 patients. The main end point was event-free survival (EFS). Analysis of chlorambucil versus the combination arm was performed and reported separately before any analysis of the third arm. Results At a median follow-up of 7.4 years, addition of rituximab to chlorambucil led to significantly better EFS (hazard ratio, 0.54; 95% CI, 0.38 to 0.77). EFS at 5 years was 51% (95% CI, 42 to 60) with chlorambucil alone, 50% (95% CI, 42 to 59) with rituximab alone, and 68% (95% CI, 60 to 76) with the combination ( P = .0009). Progression-free survival was also significantly better with the combination ( P = .0119). Five-year overall survival was approximately 90% in each arm. All treatments were well tolerated. No unexpected toxicities were recorded. Conclusion Rituximab in combination with chlorambucil demonstrated superior efficacy in mucosa-associated lymphoid tissue lymphoma; however, improvements in EFS and progression-free survival did not translate into longer overall survival.

AB - There is no consensus on the optimal systemic treatment of patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The IELSG-19 phase III study, to our knowledge, was the first such study to address the question of first-line treatment in a randomized trial. Patients and Methods Eligible patients were initially randomly assigned (1:1 ratio) to receive either chlorambucil monotherapy (6 mg/m2/d orally on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18, and 21 to 22) or a combination of chlorambucil (same schedule as above) and rituximab (375 mg/m2 intravenously on day 1 of weeks 1, 2, 3, 4, 9, 13, 17, and 21). After the planned enrollment of 252 patients, the protocol was amended to continue with a three-arm design (1:1:6 ratio), with a new arm that included rituximab alone (same schedule as the combination arm) and with a final sample size of 454 patients. The main end point was event-free survival (EFS). Analysis of chlorambucil versus the combination arm was performed and reported separately before any analysis of the third arm. Results At a median follow-up of 7.4 years, addition of rituximab to chlorambucil led to significantly better EFS (hazard ratio, 0.54; 95% CI, 0.38 to 0.77). EFS at 5 years was 51% (95% CI, 42 to 60) with chlorambucil alone, 50% (95% CI, 42 to 59) with rituximab alone, and 68% (95% CI, 60 to 76) with the combination ( P = .0009). Progression-free survival was also significantly better with the combination ( P = .0119). Five-year overall survival was approximately 90% in each arm. All treatments were well tolerated. No unexpected toxicities were recorded. Conclusion Rituximab in combination with chlorambucil demonstrated superior efficacy in mucosa-associated lymphoid tissue lymphoma; however, improvements in EFS and progression-free survival did not translate into longer overall survival.

U2 - 10.1200/JCO.2016.70.6994

DO - 10.1200/JCO.2016.70.6994

M3 - Article

VL - 35

SP - 1905

EP - 1912

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 17

ER -