Prediction Model for Cereblon Expression in Bone Marrow Plasma Cells Based on Blood Markers in Multiple Myeloma Patients

Byung Hyun Lee, Ka Won Kang, Min Ji Jeon, Eun Sang Yu, Dae Sik Kim, Se Ryeon Lee, Hwa Jung Sung, Yong Park, Chul Won Choi, Byung Soo Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Cereblon (CRBN) is a direct target of immunomodulatory drugs (IMiDs) and is known to be sensitive and responsive to IMiD therapy. We evaluated CRBN expression in bone marrow plasma cells and analyzed whether CRBN expression was associated with multiple myeloma prognosis. Lastly, we developed a nomogram model for predicting high CRBN expression based on clinically significant blood markers. Methods: We evaluated 143 multiple myeloma patients (internal dataset) who underwent bone marrow examinations. For evaluating the prognostic ability of the nomogram model, two external cohorts (235 patients in external dataset 1 and 156 patients in external dataset 2) were analyzed. The expression of CRBN in bone marrow aspirate samples was evaluated using immunohistochemistry. High CRBN expression was defined as the study-defined H-score ≥6. Results: In the high CRBN group, the median progression-free survival (PFS) and overall survival (OS) of patients receiving the IMiD-based therapy and non-IMiD therapy were 29 and 10 months for PFS, and NR (not reached) and 54 months for OS, respectively. IMiD-based therapy was significantly associated with better PFS and OS outcomes. High CRBN expression was independently predicted by female sex, high serum free-light chain (FLC) ratio, higher serum M-protein level, and higher β2-microglobulin level. Based on these results, we constructed a new nomogram model to predict high CRBN expression and the effectiveness of IMiD therapy in multiple myeloma. Conclusion: This nomogram could improve the prognostic evaluation of myeloma patients exhibiting high CRBN expression treated with IMiD therapy and might help provide personalized treatment strategies to clinicians.

Original languageEnglish
Article number687361
JournalFrontiers in Oncology
Volume11
DOIs
Publication statusPublished - 2021 Jul 14

Bibliographical note

Funding Information:
This research was supported by the Bio and Medical Technology Development Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT (NRF-2017M3A9C8060403).

Funding Information:
The authors thank the members of the Korea University, Anam Hospital Clinical Trial Center, especially Jin Wha Lee, for her help in collecting the clinical data, and Chan Min Lee, for preparing the bone marrow samples. The authors also thank Seung-Yeon Oh for technical support in the IHC, and Jae Ho Han for help in interpretation of pathology.

Publisher Copyright:
© Copyright © 2021 Lee, Kang, Jeon, Yu, Kim, Lee, Sung, Park, Choi and Kim.

Keywords

  • cereblon
  • immunomodulatory therapy
  • multiple myeloma
  • nomograms
  • prognosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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