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

3 Scopus citations

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)
Pages (from-to)225-234
Number of pages10
JournalBritish Journal of Haematology
Volume183
Issue number2
DOIs
StatePublished - Oct 2018

Keywords

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

ASJC Scopus subject areas

  • Hematology

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    Holte, H., Beiske, K., Boyle, M., Trøen, G., Blaker, Y. N., Myklebust, J., Kvaløy, S., Rosenwald, A., Lingjærde, O. C., Rimsza, L. M., Smeland, E. B., Scott, D. W., & 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, 183(2), 225-234. https://doi.org/10.1111/bjh.15518