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

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

doi:10.3389/fonc.2021.687361

Abstract

BackgroundCereblon (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.MethodsWe 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.ResultsIn 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.ConclusionThis 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.

Highlights

Cereblon (CRBN) is a multifunctional protein located in the cytoplasm, nucleus, and peripheral membranes of the human tissues [1]
This study aimed to evaluate expression of CRBN in bone marrow plasma cells and investigate whether CRBN is related to the prognosis of multiple myeloma
We examined the 143 bone marrow specimens for CRBN expression and clinical features

Summary

Introduction

Cereblon (CRBN) is a multifunctional protein located in the cytoplasm, nucleus, and peripheral membranes of the human tissues [1]. CRBN is closely related to the proliferation and metabolism of normal cells as well as tumor cells and is responsible for antiproliferative activities of immunomodulatory drugs (IMiDs) [2]. CRBN is a direct target of IMiDs and is associated with patient sensitivity and response to IMiD therapy; providing a theoretical basis for individual clinical treatments [1]. IMiDs (thalidomide, lenalidomide, or pomalidomide) provide the backbone of multiple myeloma treatment for both newly diagnosed and relapsed diseases [5,6,7] including maintenance therapy [8] and can be combined with new treatment strategies that themselves have immunomodulatory activities [9]. Cereblon (CRBN) is a direct target of immunomodulatory drugs (IMiDs) and is known to be sensitive and responsive to IMiD therapy. We developed a nomogram model for predicting high CRBN expression based on clinically significant blood markers

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