c-MYC expression and maturity phenotypes are associated with outcome benefit from addition of ixazomib to lenalidomide-dexamethasone in myeloma

Alessandra Di Bacco, Nizar J. Bahlis, Nikhil C. Munshi, Hervé Avet-Loiseau, Tamás Masszi, Luísa Viterbo, Ludek Pour, Peter Ganly, Michele Cavo, Christian Langer, Shaji K. Kumar, S. Vincent Rajkumar, Jonathan J. Keats, Deborah Berg, Jianchang Lin, Bin Li, Sunita Badola, Lei Shen, Jacob Zhang, Dixie Lee EsseltineKatarina Luptakova, Helgi van de Velde, Paul G. Richardson, Philippe Moreau

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Objectives: In the TOURMALINE-MM1 phase 3 trial in relapsed/refractory multiple myeloma, ixazomib-lenalidomide-dexamethasone (IRd) showed different magnitudes of progression-free survival (PFS) benefit vs placebo-Rd according to number and type of prior therapies, with greater benefit seen in patients with >1 prior line of therapy or 1 prior line of therapy without stem cell transplantation (SCT). Methods: RNA sequencing data were used to investigate the basis of these differences. Results: The PFS benefit of IRd vs placebo-Rd was greater in patients with tumors expressing high c-MYC levels (median not reached vs 11.3 months; hazard ratio [HR] 0.42; 95% CI, 0.26, 0.66; P <.001) compared with in those expressing low c-MYC levels (median 20.6 vs 16.6 months; HR 0.75; 95% CI, 0.42, 1.2). Expression of c-MYC in tumors varied based on the number and type of prior therapy received, with the lowest levels observed in tumors of patients who had received 1 prior line of therapy including SCT. These tumors also had higher expression levels of CD19 and CD81. Conclusions: PFS analyses suggest that lenalidomide and ixazomib target tumors with different levels of c-MYC, CD19, and CD81 expression, thus providing a potential rationale for the differential benefits observed in the TOURMALINE-MM1 study. This trial was registered at www.clinicaltrials.gov as: NCT01564537.

Original languageEnglish (US)
Pages (from-to)35-46
Number of pages12
JournalEuropean Journal of Haematology
Volume105
Issue number1
DOIs
StatePublished - Jul 1 2020

Keywords

  • RNA sequencing
  • c-myc Proto-Oncogenes
  • multiple myeloma
  • mutation
  • progression-free survival

ASJC Scopus subject areas

  • Hematology

Fingerprint Dive into the research topics of 'c-MYC expression and maturity phenotypes are associated with outcome benefit from addition of ixazomib to lenalidomide-dexamethasone in myeloma'. Together they form a unique fingerprint.

  • Cite this

    Di Bacco, A., Bahlis, N. J., Munshi, N. C., Avet-Loiseau, H., Masszi, T., Viterbo, L., Pour, L., Ganly, P., Cavo, M., Langer, C., Kumar, S. K., Rajkumar, S. V., Keats, J. J., Berg, D., Lin, J., Li, B., Badola, S., Shen, L., Zhang, J., ... Moreau, P. (2020). c-MYC expression and maturity phenotypes are associated with outcome benefit from addition of ixazomib to lenalidomide-dexamethasone in myeloma. European Journal of Haematology, 105(1), 35-46. https://doi.org/10.1111/ejh.13405