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

Br J Haematol. 2018 Oct;183(2):225-234. doi: 10.1111/bjh.15518. Epub 2018 Aug 6.

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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biopsy
  • Cell Proliferation
  • Female
  • Gene Expression Profiling / methods
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Kaplan-Meier Estimate
  • Lymphoma, Mantle-Cell / diagnosis
  • Lymphoma, Mantle-Cell / drug therapy*
  • Lymphoma, Mantle-Cell / genetics*
  • Lymphoma, Mantle-Cell / pathology
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Neoplasm / genetics
  • Risk Factors

Substances

  • RNA, Neoplasm