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

Mark Hertzberg, Maher K. Gandhi, Judith Trotman, Belinda Butcher, John Taper, Amanda Johnston, Devinder Gill, Shir-Jing Ho, Gavin Cull, Keith Fay, Geoff Chong, Andrew Grigg, Ian D. Lewis, Sam Milliken, William Renwick, Uwe Hahn, Robin Filshie, George Kannourakis, Anne-Marie Watson, Pauline Warburton & 5 others Andrew Wirth, John F. S. Seymour, Michael S. Hofman, Rodney J. Hicks, ALLG

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

In the treatment of diffuse large B-cell lymphoma a persistently positive [18F]fluorodeoxyglucose positron emission tomography (PET) scan typically carries a poor prognosis. In this prospective multi-center phase 2 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 an historically unfavourable 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 to 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 PET-positive, 32 of whom completed R-ICE and 90Y-ibritumomab tiuxetan-BEAM. At a median follow-up of 35 months, the 2-year progression free survival for PET-positive patients was 67%, a rate similar to that for PET-negative patients treated with R-CHOP-14 (74%, P=0.11); overall survival was 78% and 88% (P=0.11), respectively. In an exploratory analysis, progression free and overall survival were markedly superior for PET-positive Deauville score 4 versus score 5 (P=0.0002 and P=0.001). Hence, diffuse large B-cell lymphoma patients who are PET-positive after 4 cycles of R-CHOP-14 and switched to R-ICE and 90Y-ibritumomab tiuxetan-BEAM achieve favourable survival outcomes similar to that for PET-negative R-CHOP-14-treated patients. Further studies are warranted to confirm these promising results. (ACTRN12609001077257)

Original languageEnglish
Pages (from-to)356-363
Number of pages8
JournalHaematologica
Volume102
Issue number2
DOIs
Publication statusPublished - Feb 2017
Externally publishedYes

Cite this

Hertzberg, Mark ; Gandhi, Maher K. ; Trotman, Judith ; Butcher, Belinda ; Taper, John ; Johnston, Amanda ; Gill, Devinder ; Ho, Shir-Jing ; Cull, Gavin ; Fay, Keith ; Chong, Geoff ; Grigg, Andrew ; Lewis, Ian D. ; Milliken, Sam ; Renwick, William ; Hahn, Uwe ; Filshie, Robin ; Kannourakis, George ; Watson, Anne-Marie ; Warburton, Pauline ; Wirth, Andrew ; Seymour, John F. S. ; Hofman, Michael S. ; Hicks, Rodney J. ; ALLG. / 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. In: Haematologica. 2017 ; Vol. 102, No. 2. pp. 356-363.
@article{718146baaf054de28792ccd37ed8871e,
title = "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 = "In the treatment of diffuse large B-cell lymphoma a persistently positive [18F]fluorodeoxyglucose positron emission tomography (PET) scan typically carries a poor prognosis. In this prospective multi-center phase 2 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 an historically unfavourable 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 to 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 PET-positive, 32 of whom completed R-ICE and 90Y-ibritumomab tiuxetan-BEAM. At a median follow-up of 35 months, the 2-year progression free survival for PET-positive patients was 67{\%}, a rate similar to that for PET-negative patients treated with R-CHOP-14 (74{\%}, P=0.11); overall survival was 78{\%} and 88{\%} (P=0.11), respectively. In an exploratory analysis, progression free and overall survival were markedly superior for PET-positive Deauville score 4 versus score 5 (P=0.0002 and P=0.001). Hence, diffuse large B-cell lymphoma patients who are PET-positive after 4 cycles of R-CHOP-14 and switched to R-ICE and 90Y-ibritumomab tiuxetan-BEAM achieve favourable survival outcomes similar to that for PET-negative R-CHOP-14-treated patients. Further studies are warranted to confirm these promising results. (ACTRN12609001077257)",
keywords = "POSITRON-EMISSION-TOMOGRAPHY, NON-HODGKINS-LYMPHOMA, INTERNATIONAL PROGNOSTIC INDEX, Y-90 IBRITUMOMAB TIUXETAN, HIGH-DOSE CHEMOTHERAPY, SUV-BASED ASSESSMENT, PHASE-II TRIAL, FDG-PET, RESPONSE ASSESSMENT, AGGRESSIVE LYMPHOMA",
author = "Mark Hertzberg and Gandhi, {Maher K.} and Judith Trotman and Belinda Butcher and John Taper and Amanda Johnston and Devinder Gill and Shir-Jing Ho and Gavin Cull and Keith Fay and Geoff Chong and Andrew Grigg and Lewis, {Ian D.} and Sam Milliken and William Renwick and Uwe Hahn and Robin Filshie and George Kannourakis and Anne-Marie Watson and Pauline Warburton and Andrew Wirth and Seymour, {John F. S.} and Hofman, {Michael S.} and Hicks, {Rodney J.} and ALLG",
year = "2017",
month = "2",
doi = "10.3324/haematol.2016.154039",
language = "English",
volume = "102",
pages = "356--363",
journal = "Haematologica",
issn = "0390-6078",
publisher = "Ferrata Storti Foundation",
number = "2",

}

Hertzberg, M, Gandhi, MK, Trotman, J, Butcher, B, Taper, J, Johnston, A, Gill, D, Ho, S-J, Cull, G, Fay, K, Chong, G, Grigg, A, Lewis, ID, Milliken, S, Renwick, W, Hahn, U, Filshie, R, Kannourakis, G, Watson, A-M, Warburton, P, Wirth, A, Seymour, JFS, Hofman, MS, Hicks, RJ & ALLG 2017, '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' Haematologica, vol. 102, no. 2, pp. 356-363. https://doi.org/10.3324/haematol.2016.154039

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. / Hertzberg, Mark; Gandhi, Maher K.; Trotman, Judith; Butcher, Belinda; Taper, John; Johnston, Amanda; Gill, Devinder; Ho, Shir-Jing; Cull, Gavin; Fay, Keith; Chong, Geoff; Grigg, Andrew; Lewis, Ian D.; Milliken, Sam; Renwick, William; Hahn, Uwe; Filshie, Robin; Kannourakis, George; Watson, Anne-Marie; Warburton, Pauline; Wirth, Andrew; Seymour, John F. S.; Hofman, Michael S.; Hicks, Rodney J.; ALLG.

In: Haematologica, Vol. 102, No. 2, 02.2017, p. 356-363.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Hertzberg, Mark

AU - Gandhi, Maher K.

AU - Trotman, Judith

AU - Butcher, Belinda

AU - Taper, John

AU - Johnston, Amanda

AU - Gill, Devinder

AU - Ho, Shir-Jing

AU - Cull, Gavin

AU - Fay, Keith

AU - Chong, Geoff

AU - Grigg, Andrew

AU - Lewis, Ian D.

AU - Milliken, Sam

AU - Renwick, William

AU - Hahn, Uwe

AU - Filshie, Robin

AU - Kannourakis, George

AU - Watson, Anne-Marie

AU - Warburton, Pauline

AU - Wirth, Andrew

AU - Seymour, John F. S.

AU - Hofman, Michael S.

AU - Hicks, Rodney J.

AU - ALLG

PY - 2017/2

Y1 - 2017/2

N2 - In the treatment of diffuse large B-cell lymphoma a persistently positive [18F]fluorodeoxyglucose positron emission tomography (PET) scan typically carries a poor prognosis. In this prospective multi-center phase 2 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 an historically unfavourable 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 to 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 PET-positive, 32 of whom completed R-ICE and 90Y-ibritumomab tiuxetan-BEAM. At a median follow-up of 35 months, the 2-year progression free survival for PET-positive patients was 67%, a rate similar to that for PET-negative patients treated with R-CHOP-14 (74%, P=0.11); overall survival was 78% and 88% (P=0.11), respectively. In an exploratory analysis, progression free and overall survival were markedly superior for PET-positive Deauville score 4 versus score 5 (P=0.0002 and P=0.001). Hence, diffuse large B-cell lymphoma patients who are PET-positive after 4 cycles of R-CHOP-14 and switched to R-ICE and 90Y-ibritumomab tiuxetan-BEAM achieve favourable survival outcomes similar to that for PET-negative R-CHOP-14-treated patients. Further studies are warranted to confirm these promising results. (ACTRN12609001077257)

AB - In the treatment of diffuse large B-cell lymphoma a persistently positive [18F]fluorodeoxyglucose positron emission tomography (PET) scan typically carries a poor prognosis. In this prospective multi-center phase 2 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 an historically unfavourable 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 to 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 PET-positive, 32 of whom completed R-ICE and 90Y-ibritumomab tiuxetan-BEAM. At a median follow-up of 35 months, the 2-year progression free survival for PET-positive patients was 67%, a rate similar to that for PET-negative patients treated with R-CHOP-14 (74%, P=0.11); overall survival was 78% and 88% (P=0.11), respectively. In an exploratory analysis, progression free and overall survival were markedly superior for PET-positive Deauville score 4 versus score 5 (P=0.0002 and P=0.001). Hence, diffuse large B-cell lymphoma patients who are PET-positive after 4 cycles of R-CHOP-14 and switched to R-ICE and 90Y-ibritumomab tiuxetan-BEAM achieve favourable survival outcomes similar to that for PET-negative R-CHOP-14-treated patients. Further studies are warranted to confirm these promising results. (ACTRN12609001077257)

KW - POSITRON-EMISSION-TOMOGRAPHY

KW - NON-HODGKINS-LYMPHOMA

KW - INTERNATIONAL PROGNOSTIC INDEX

KW - Y-90 IBRITUMOMAB TIUXETAN

KW - HIGH-DOSE CHEMOTHERAPY

KW - SUV-BASED ASSESSMENT

KW - PHASE-II TRIAL

KW - FDG-PET

KW - RESPONSE ASSESSMENT

KW - AGGRESSIVE LYMPHOMA

U2 - 10.3324/haematol.2016.154039

DO - 10.3324/haematol.2016.154039

M3 - Article

VL - 102

SP - 356

EP - 363

JO - Haematologica

JF - Haematologica

SN - 0390-6078

IS - 2

ER -