The MCL35 gene expression proliferation assay predicts high-risk MCL patients in a Norwegian cohort of younger patients given intensive first line therapy

Harald Holte, Klaus Beiske, Merrill Boyle, Gunhild Trøen, Yngvild N. Blaker, June Myklebust, Sunniva Kvaløy, Andreas Rosenwald, Ole C. Lingjærde, Lisa M Rimsza, Erlend B. Smeland, David W. Scott, Arne Kolstad

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Patients with mantle cell lymphoma (MCL) generally have a dismal prognosis. Intensified induction treatment with rituximab and high dose cytarabine (R_HDAC), and consolidation with high-dose therapy with autologous stem cell support has resulted in 10-year overall survival (OS) higher than 60%. However, the clinical course varies. Diagnostic tools capable of stratifying patients include the MCL International Prognostic Index (MIPI), gene expression-based proliferation signature, Ki-67 proliferation index or tumour cell morphology. Here, we tested the performance of a newly developed Nanostring-based RNA expression-based proliferation assay (MCL35) on formalin-fixed paraffin-embedded tumour tissue from younger patients recruited in or treated according to Nordic MCL protocols compared to the prognosticators listed above. Seventy-four patients were included and the assay performed well in all cases except four, which had inadequate RNA quality. The patients were evenly distributed in the MCL35 low-, intermediate- and high-risk categories. MCL35 low- and intermediate- risk groups had overlapping progression-free survival (PFS), while patients in the high-risk category had significantly inferior PFS. Combining MCL35 with MIPI or the MIPI-C (MIPI with the addition of binary Ki67 score +/−30%) showed a better discrimination than either assessment alone. In conclusion, the MCL35 assay alone or combined with MIPI or MIPI-C scores can identify patients who still have a dismal outcome despite intensified treatment.

Original languageEnglish (US)
JournalBritish Journal of Haematology
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

Mantle-Cell Lymphoma
Gene Expression
Therapeutics
Disease-Free Survival
RNA
Cytarabine
Paraffin
Formaldehyde
Neoplasms
Stem Cells
Survival

Keywords

  • formalin-fixed, paraffin-embedded tissue
  • gene expression
  • mantle cell lymphoma
  • prediction
  • therapy

ASJC Scopus subject areas

  • Hematology

Cite this

The MCL35 gene expression proliferation assay predicts high-risk MCL patients in a Norwegian cohort of younger patients given intensive first line therapy. / Holte, Harald; Beiske, Klaus; Boyle, Merrill; Trøen, Gunhild; Blaker, Yngvild N.; Myklebust, June; Kvaløy, Sunniva; Rosenwald, Andreas; Lingjærde, Ole C.; Rimsza, Lisa M; Smeland, Erlend B.; Scott, David W.; Kolstad, Arne.

In: British Journal of Haematology, 01.01.2018.

Research output: Contribution to journalArticle

Holte, H, Beiske, K, Boyle, M, Trøen, G, Blaker, YN, Myklebust, J, Kvaløy, S, Rosenwald, A, Lingjærde, OC, Rimsza, LM, Smeland, EB, Scott, DW & Kolstad, A 2018, 'The MCL35 gene expression proliferation assay predicts high-risk MCL patients in a Norwegian cohort of younger patients given intensive first line therapy', British Journal of Haematology. https://doi.org/10.1111/bjh.15518
Holte, Harald ; Beiske, Klaus ; Boyle, Merrill ; Trøen, Gunhild ; Blaker, Yngvild N. ; Myklebust, June ; Kvaløy, Sunniva ; Rosenwald, Andreas ; Lingjærde, Ole C. ; Rimsza, Lisa M ; Smeland, Erlend B. ; Scott, David W. ; Kolstad, Arne. / The MCL35 gene expression proliferation assay predicts high-risk MCL patients in a Norwegian cohort of younger patients given intensive first line therapy. In: British Journal of Haematology. 2018.
@article{837b0831555f419fa7b03ed0e579de31,
title = "The MCL35 gene expression proliferation assay predicts high-risk MCL patients in a Norwegian cohort of younger patients given intensive first line therapy",
abstract = "Patients with mantle cell lymphoma (MCL) generally have a dismal prognosis. Intensified induction treatment with rituximab and high dose cytarabine (R_HDAC), and consolidation with high-dose therapy with autologous stem cell support has resulted in 10-year overall survival (OS) higher than 60{\%}. However, the clinical course varies. Diagnostic tools capable of stratifying patients include the MCL International Prognostic Index (MIPI), gene expression-based proliferation signature, Ki-67 proliferation index or tumour cell morphology. Here, we tested the performance of a newly developed Nanostring-based RNA expression-based proliferation assay (MCL35) on formalin-fixed paraffin-embedded tumour tissue from younger patients recruited in or treated according to Nordic MCL protocols compared to the prognosticators listed above. Seventy-four patients were included and the assay performed well in all cases except four, which had inadequate RNA quality. The patients were evenly distributed in the MCL35 low-, intermediate- and high-risk categories. MCL35 low- and intermediate- risk groups had overlapping progression-free survival (PFS), while patients in the high-risk category had significantly inferior PFS. Combining MCL35 with MIPI or the MIPI-C (MIPI with the addition of binary Ki67 score +/−30{\%}) showed a better discrimination than either assessment alone. In conclusion, the MCL35 assay alone or combined with MIPI or MIPI-C scores can identify patients who still have a dismal outcome despite intensified treatment.",
keywords = "formalin-fixed, paraffin-embedded tissue, gene expression, mantle cell lymphoma, prediction, therapy",
author = "Harald Holte and Klaus Beiske and Merrill Boyle and Gunhild Tr{\o}en and Blaker, {Yngvild N.} and June Myklebust and Sunniva Kval{\o}y and Andreas Rosenwald and Lingj{\ae}rde, {Ole C.} and Rimsza, {Lisa M} and Smeland, {Erlend B.} and Scott, {David W.} and Arne Kolstad",
year = "2018",
month = "1",
day = "1",
doi = "10.1111/bjh.15518",
language = "English (US)",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - The MCL35 gene expression proliferation assay predicts high-risk MCL patients in a Norwegian cohort of younger patients given intensive first line therapy

AU - Holte, Harald

AU - Beiske, Klaus

AU - Boyle, Merrill

AU - Trøen, Gunhild

AU - Blaker, Yngvild N.

AU - Myklebust, June

AU - Kvaløy, Sunniva

AU - Rosenwald, Andreas

AU - Lingjærde, Ole C.

AU - Rimsza, Lisa M

AU - Smeland, Erlend B.

AU - Scott, David W.

AU - Kolstad, Arne

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Patients with mantle cell lymphoma (MCL) generally have a dismal prognosis. Intensified induction treatment with rituximab and high dose cytarabine (R_HDAC), and consolidation with high-dose therapy with autologous stem cell support has resulted in 10-year overall survival (OS) higher than 60%. However, the clinical course varies. Diagnostic tools capable of stratifying patients include the MCL International Prognostic Index (MIPI), gene expression-based proliferation signature, Ki-67 proliferation index or tumour cell morphology. Here, we tested the performance of a newly developed Nanostring-based RNA expression-based proliferation assay (MCL35) on formalin-fixed paraffin-embedded tumour tissue from younger patients recruited in or treated according to Nordic MCL protocols compared to the prognosticators listed above. Seventy-four patients were included and the assay performed well in all cases except four, which had inadequate RNA quality. The patients were evenly distributed in the MCL35 low-, intermediate- and high-risk categories. MCL35 low- and intermediate- risk groups had overlapping progression-free survival (PFS), while patients in the high-risk category had significantly inferior PFS. Combining MCL35 with MIPI or the MIPI-C (MIPI with the addition of binary Ki67 score +/−30%) showed a better discrimination than either assessment alone. In conclusion, the MCL35 assay alone or combined with MIPI or MIPI-C scores can identify patients who still have a dismal outcome despite intensified treatment.

AB - Patients with mantle cell lymphoma (MCL) generally have a dismal prognosis. Intensified induction treatment with rituximab and high dose cytarabine (R_HDAC), and consolidation with high-dose therapy with autologous stem cell support has resulted in 10-year overall survival (OS) higher than 60%. However, the clinical course varies. Diagnostic tools capable of stratifying patients include the MCL International Prognostic Index (MIPI), gene expression-based proliferation signature, Ki-67 proliferation index or tumour cell morphology. Here, we tested the performance of a newly developed Nanostring-based RNA expression-based proliferation assay (MCL35) on formalin-fixed paraffin-embedded tumour tissue from younger patients recruited in or treated according to Nordic MCL protocols compared to the prognosticators listed above. Seventy-four patients were included and the assay performed well in all cases except four, which had inadequate RNA quality. The patients were evenly distributed in the MCL35 low-, intermediate- and high-risk categories. MCL35 low- and intermediate- risk groups had overlapping progression-free survival (PFS), while patients in the high-risk category had significantly inferior PFS. Combining MCL35 with MIPI or the MIPI-C (MIPI with the addition of binary Ki67 score +/−30%) showed a better discrimination than either assessment alone. In conclusion, the MCL35 assay alone or combined with MIPI or MIPI-C scores can identify patients who still have a dismal outcome despite intensified treatment.

KW - formalin-fixed, paraffin-embedded tissue

KW - gene expression

KW - mantle cell lymphoma

KW - prediction

KW - therapy

UR - http://www.scopus.com/inward/record.url?scp=85052628103&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85052628103&partnerID=8YFLogxK

U2 - 10.1111/bjh.15518

DO - 10.1111/bjh.15518

M3 - Article

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

ER -