Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma

Tarec Christoffer El-Galaly; Chan Yoon Cheah; Mette Dahl Bendtsen; Grzegorz S. Nowakowski; Roopesh Kansara; Kerry J. Savage; Joseph M. Connors; Laurie H. Sehn; Neta Goldschmidt; Adir Shaulov; Umar Farooq; Brian K. Link; Andrés J.M. Ferreri; Teresa Calimeri; Caterina Cecchetti; Eldad J. Dann; Carrie A. Thompson; Tsofia Inbar; Matthew J. Maurer; Inger Lise Gade; Maja Bech Juul; Jakob W. Hansen; Staffan Holmberg; Thomas S. Larsen; Sabrina Cordua; N. George Mikhaeel; Martin Hutchings; John F. Seymour; Michael Roost Clausen; Daniel Smith; Stephen Opat; Michael Gilbertson; Gita Thanarajasingam; Diego Villa

doi:10.1016/j.ejca.2018.01.073

Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma

Tarec Christoffer El-Galaly^*, Chan Yoon Cheah, Mette Dahl Bendtsen, Grzegorz S. Nowakowski, Roopesh Kansara, Kerry J. Savage, Joseph M. Connors, Laurie H. Sehn, Neta Goldschmidt, Adir Shaulov, Umar Farooq, Brian K. Link, Andrés J.M. Ferreri, Teresa Calimeri, Caterina Cecchetti, Eldad J. Dann, Carrie A. Thompson, Tsofia Inbar, Matthew J. Maurer, Inger Lise GadeMaja Bech Juul, Jakob W. Hansen, Staffan Holmberg, Thomas S. Larsen, Sabrina Cordua, N. George Mikhaeel, Martin Hutchings, John F. Seymour, Michael Roost Clausen, Daniel Smith, Stephen Opat, Michael Gilbertson, Gita Thanarajasingam, Diego Villa

^*Corresponding author for this work

25 Citations (Scopus)

Abstract

Purpose: Secondary CNS involvement (SCNS) is a profoundly adverse complication of diffuse large B-cell lymphoma. Evidence from older series indicated a median overall survival (OS) < 6 months; however, data from the immunochemotherapy era are limited. Methods: Patients diagnosed with SCNS during or after first-line immunochemotherapy were identified from databases and/or regional/national registries from three continents. Clinical information was retrospectively collected from medical records. Results: In total, 291 patients with SCNS were included. SCNS occurred as part of first relapse in 254 (87%) patients and 113 (39%) had concurrent systemic relapse. With a median post-SCNS follow-up of 48 months, the median post-SCNS OS was 3.9 months and 2-year OS rate was 20% (95% CI: 15–25). In multivariable analysis of 173 patients treated with curative/intensive therapy (such as high-dose methotrexate [HDMTX] or platinum-containing regimens), age ≤60 years, performance status 0–1, absence of combined leptomeningeal and parenchymal involvement, and SCNS occurring after completion of first-line therapy were associated with superior outcomes. Patients ≤60 years with performance status 0–1 and treated with HDMTX-based regimens for isolated parenchymal SCNS had a 2-year OS of 62% (95% CI: 36–80). In patients with isolated SCNS, the addition of rituximab to HDMTX-based regimens was associated with improved OS. Amongst patients with isolated SCNS in CR following intensive treatment, high-dose chemotherapy and autologous stem cell transplantation did not improve OS (P = 0.9). Conclusions: In this large international cohort of patients treated with first-line immunochemotherapy, outcomes following SCNS remain poor. However, a moderate proportion of patients with isolated SCNS who received intensive therapies achieved durable remissions.

Original language	English
Journal	European Journal of Cancer
Volume	93
Pages (from-to)	57-68
Number of pages	12
ISSN	0959-8049
DOIs	https://doi.org/10.1016/j.ejca.2018.01.073
Publication status	Published - 2018
Externally published	Yes

Keywords

Autologous stem cell transplant
Central nervous system
Diffuse large B-Cell lymphoma
Rituximab
Secondary CNS

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10.1016/j.ejca.2018.01.073

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El-Galaly, T. C., Cheah, C. Y., Bendtsen, M. D., Nowakowski, G. S., Kansara, R., Savage, K. J., Connors, J. M., Sehn, L. H., Goldschmidt, N., Shaulov, A., Farooq, U., Link, B. K., Ferreri, A. J. M., Calimeri, T., Cecchetti, C., Dann, E. J., Thompson, C. A., Inbar, T., Maurer, M. J., ... Villa, D. (2018). Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma. European Journal of Cancer, 93, 57-68. https://doi.org/10.1016/j.ejca.2018.01.073

El-Galaly, TC, Cheah, CY, Bendtsen, MD, Nowakowski, GS, Kansara, R, Savage, KJ, Connors, JM, Sehn, LH, Goldschmidt, N, Shaulov, A, Farooq, U, Link, BK, Ferreri, AJM, Calimeri, T, Cecchetti, C, Dann, EJ, Thompson, CA, Inbar, T, Maurer, MJ, Gade, IL, Juul, MB, Hansen, JW, Holmberg, S, Larsen, TS, Cordua, S, Mikhaeel, NG, Hutchings, M, Seymour, JF, Clausen, MR, Smith, D, Opat, S, Gilbertson, M, Thanarajasingam, G & Villa, D 2018, 'Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma', European Journal of Cancer, vol. 93, pp. 57-68. https://doi.org/10.1016/j.ejca.2018.01.073

@article{507794fbf27344d4a173ccd73504fff7,

title = "Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma",

abstract = "Purpose: Secondary CNS involvement (SCNS) is a profoundly adverse complication of diffuse large B-cell lymphoma. Evidence from older series indicated a median overall survival (OS) < 6 months; however, data from the immunochemotherapy era are limited. Methods: Patients diagnosed with SCNS during or after first-line immunochemotherapy were identified from databases and/or regional/national registries from three continents. Clinical information was retrospectively collected from medical records. Results: In total, 291 patients with SCNS were included. SCNS occurred as part of first relapse in 254 (87%) patients and 113 (39%) had concurrent systemic relapse. With a median post-SCNS follow-up of 48 months, the median post-SCNS OS was 3.9 months and 2-year OS rate was 20% (95% CI: 15–25). In multivariable analysis of 173 patients treated with curative/intensive therapy (such as high-dose methotrexate [HDMTX] or platinum-containing regimens), age ≤60 years, performance status 0–1, absence of combined leptomeningeal and parenchymal involvement, and SCNS occurring after completion of first-line therapy were associated with superior outcomes. Patients ≤60 years with performance status 0–1 and treated with HDMTX-based regimens for isolated parenchymal SCNS had a 2-year OS of 62% (95% CI: 36–80). In patients with isolated SCNS, the addition of rituximab to HDMTX-based regimens was associated with improved OS. Amongst patients with isolated SCNS in CR following intensive treatment, high-dose chemotherapy and autologous stem cell transplantation did not improve OS (P = 0.9). Conclusions: In this large international cohort of patients treated with first-line immunochemotherapy, outcomes following SCNS remain poor. However, a moderate proportion of patients with isolated SCNS who received intensive therapies achieved durable remissions.",

keywords = "Autologous stem cell transplant, Central nervous system, Diffuse large B-Cell lymphoma, Rituximab, Secondary CNS",

author = "El-Galaly, {Tarec Christoffer} and Cheah, {Chan Yoon} and Bendtsen, {Mette Dahl} and Nowakowski, {Grzegorz S.} and Roopesh Kansara and Savage, {Kerry J.} and Connors, {Joseph M.} and Sehn, {Laurie H.} and Neta Goldschmidt and Adir Shaulov and Umar Farooq and Link, {Brian K.} and Ferreri, {Andr{\'e}s J.M.} and Teresa Calimeri and Caterina Cecchetti and Dann, {Eldad J.} and Thompson, {Carrie A.} and Tsofia Inbar and Maurer, {Matthew J.} and Gade, {Inger Lise} and Juul, {Maja Bech} and Hansen, {Jakob W.} and Staffan Holmberg and Larsen, {Thomas S.} and Sabrina Cordua and Mikhaeel, {N. George} and Martin Hutchings and Seymour, {John F.} and Clausen, {Michael Roost} and Daniel Smith and Stephen Opat and Michael Gilbertson and Gita Thanarajasingam and Diego Villa",

year = "2018",

doi = "10.1016/j.ejca.2018.01.073",

language = "English",

volume = "93",

pages = "57--68",

journal = "European Journal of Cancer, Supplement",

issn = "0959-8049",

publisher = "Pergamon",

}

TY - JOUR

T1 - Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma

AU - El-Galaly, Tarec Christoffer

AU - Cheah, Chan Yoon

AU - Bendtsen, Mette Dahl

AU - Nowakowski, Grzegorz S.

AU - Kansara, Roopesh

AU - Savage, Kerry J.

AU - Connors, Joseph M.

AU - Sehn, Laurie H.

AU - Goldschmidt, Neta

AU - Shaulov, Adir

AU - Farooq, Umar

AU - Link, Brian K.

AU - Ferreri, Andrés J.M.

AU - Calimeri, Teresa

AU - Cecchetti, Caterina

AU - Dann, Eldad J.

AU - Thompson, Carrie A.

AU - Inbar, Tsofia

AU - Maurer, Matthew J.

AU - Gade, Inger Lise

AU - Juul, Maja Bech

AU - Hansen, Jakob W.

AU - Holmberg, Staffan

AU - Larsen, Thomas S.

AU - Cordua, Sabrina

AU - Mikhaeel, N. George

AU - Hutchings, Martin

AU - Seymour, John F.

AU - Clausen, Michael Roost

AU - Smith, Daniel

AU - Opat, Stephen

AU - Gilbertson, Michael

AU - Thanarajasingam, Gita

AU - Villa, Diego

PY - 2018

Y1 - 2018

N2 - Purpose: Secondary CNS involvement (SCNS) is a profoundly adverse complication of diffuse large B-cell lymphoma. Evidence from older series indicated a median overall survival (OS) < 6 months; however, data from the immunochemotherapy era are limited. Methods: Patients diagnosed with SCNS during or after first-line immunochemotherapy were identified from databases and/or regional/national registries from three continents. Clinical information was retrospectively collected from medical records. Results: In total, 291 patients with SCNS were included. SCNS occurred as part of first relapse in 254 (87%) patients and 113 (39%) had concurrent systemic relapse. With a median post-SCNS follow-up of 48 months, the median post-SCNS OS was 3.9 months and 2-year OS rate was 20% (95% CI: 15–25). In multivariable analysis of 173 patients treated with curative/intensive therapy (such as high-dose methotrexate [HDMTX] or platinum-containing regimens), age ≤60 years, performance status 0–1, absence of combined leptomeningeal and parenchymal involvement, and SCNS occurring after completion of first-line therapy were associated with superior outcomes. Patients ≤60 years with performance status 0–1 and treated with HDMTX-based regimens for isolated parenchymal SCNS had a 2-year OS of 62% (95% CI: 36–80). In patients with isolated SCNS, the addition of rituximab to HDMTX-based regimens was associated with improved OS. Amongst patients with isolated SCNS in CR following intensive treatment, high-dose chemotherapy and autologous stem cell transplantation did not improve OS (P = 0.9). Conclusions: In this large international cohort of patients treated with first-line immunochemotherapy, outcomes following SCNS remain poor. However, a moderate proportion of patients with isolated SCNS who received intensive therapies achieved durable remissions.

AB - Purpose: Secondary CNS involvement (SCNS) is a profoundly adverse complication of diffuse large B-cell lymphoma. Evidence from older series indicated a median overall survival (OS) < 6 months; however, data from the immunochemotherapy era are limited. Methods: Patients diagnosed with SCNS during or after first-line immunochemotherapy were identified from databases and/or regional/national registries from three continents. Clinical information was retrospectively collected from medical records. Results: In total, 291 patients with SCNS were included. SCNS occurred as part of first relapse in 254 (87%) patients and 113 (39%) had concurrent systemic relapse. With a median post-SCNS follow-up of 48 months, the median post-SCNS OS was 3.9 months and 2-year OS rate was 20% (95% CI: 15–25). In multivariable analysis of 173 patients treated with curative/intensive therapy (such as high-dose methotrexate [HDMTX] or platinum-containing regimens), age ≤60 years, performance status 0–1, absence of combined leptomeningeal and parenchymal involvement, and SCNS occurring after completion of first-line therapy were associated with superior outcomes. Patients ≤60 years with performance status 0–1 and treated with HDMTX-based regimens for isolated parenchymal SCNS had a 2-year OS of 62% (95% CI: 36–80). In patients with isolated SCNS, the addition of rituximab to HDMTX-based regimens was associated with improved OS. Amongst patients with isolated SCNS in CR following intensive treatment, high-dose chemotherapy and autologous stem cell transplantation did not improve OS (P = 0.9). Conclusions: In this large international cohort of patients treated with first-line immunochemotherapy, outcomes following SCNS remain poor. However, a moderate proportion of patients with isolated SCNS who received intensive therapies achieved durable remissions.

KW - Autologous stem cell transplant

KW - Central nervous system

KW - Diffuse large B-Cell lymphoma

KW - Rituximab

KW - Secondary CNS

U2 - 10.1016/j.ejca.2018.01.073

DO - 10.1016/j.ejca.2018.01.073

M3 - Journal article

C2 - 29477102

AN - SCOPUS:85042330319

SN - 0959-8049

VL - 93

SP - 57

EP - 68

JO - European Journal of Cancer, Supplement

JF - European Journal of Cancer, Supplement

ER -

Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma

Abstract

Keywords

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