title: Thalidomide-based induction regimens are as effective as bortezomib-based regimens in elderly patients with multiple myeloma with cereblon expression.
abstract: Cereblon (CRBN) has been identified as a primary target of immunomodulatory drugs and is considered a biomarker for the prediction of outcomes after thalidomide- or lenalidomide-based treatments. In this study, we evaluated CRBN expression in bone marrow (BM) tissue at diagnosis and investigated the relationship between CRBN expression and treatment outcomes after thalidomide- or bortezomib-based front-line therapies in 89 elderly patients with multiple myeloma (MM). CRBN expression at the time of diagnosis was evaluated with immunohistochemical (IHC) staining for myeloma cells in paraffin wax-embedded BM tissue. CRBN-immunostained slides were scored by intensity and diffuseness, and a total score of >6 was defined as CRBN-positive (CRBN(+)). Thirty-eight patients (45.2 %) were CRBN(+). Among patients treated with thalidomide-based regimens, CRBN(+) patients showed a better treatment response than did CRBN-negative patients (35.0 vs. 11.8 % complete response rate, respectively; HR = 4.038, P = 0.137). During a median follow-up of 31.8 months, patients treated with bortezomib-based regimens had a longer time to progression (TTP) than did patients treated with thalidomide-based regimens (15.6 vs. 13.2 months, respectively; P = 0.047), but early mortality occurred frequently in patients treated with bortezomib-based regimens. Additionally, there was no significant difference in survival outcomes between thalidomide- and bortezomib-based regimens in CRBN(+) patients (median TTP, 13.8 vs. 15.6 months, respectively; P = 0.842 and median OS, 39.3 vs. 30.1 months, respectively; P = 0.074). These data suggest that thalidomide-based regimens are as effective as bortezomib-based regimens in elderly patients with MM who are CRBN(+). Thus, CRBN positivity, by IHC staining, may be useful in deciding appropriate treatment options in elderly patients with MM.
authors.affiliation: Departments of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Laboratory Medicine, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Laboratory Medicine, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea.
authors.forename: Myung-Geun
authors.initials: MG
authors.lastname: Shin
authors.affiliation: Departments of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
authors.forename: Seung-Shin
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Urology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea.
authors.forename: Eu Chang
authors.initials: EC
authors.lastname: Hwang
authors.affiliation: Neurosurgery, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea.
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Jung
authors.affiliation: Departments of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
authors.forename: Min-Seok
authors.initials: MS
authors.lastname: Cho
authors.affiliation: Departments of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
authors.forename: Deok-Hwan
authors.initials: DH
authors.lastname: Yang
authors.affiliation: Departments of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
authors.forename: Jae-Sook
authors.initials: JS
authors.lastname: Ahn
authors.affiliation: Departments of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
authors.forename: Yeo-Kyeoung
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Departments of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Departments of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea. drjejung@chonnam.ac.kr.
authors.forename: Je-Jung
authors.initials: JJ
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000378:metabolism; D000069286:Bortezomib / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology; D053208:Kaplan-Meier Estimate; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis*; D010447:Peptide Hydrolases / Q000032:analysis / Q000096:biosynthesis*; D011239:Prednisolone / Q000008:administration & dosage; D012074:Remission Induction; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000494:pharmacology; D016896:Treatment Outcome; D044767:Ubiquitin-Protein Ligases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C502543:CRBN protein, human; D007155:Immunologic Factors; D009363:Neoplasm Proteins; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D003520:Cyclophosphamide; D011239:Prednisolone; D044767:Ubiquitin-Protein Ligases; D010447:Peptide Hydrolases; D008558:Melphalan
keywords: Cereblon; Elderly; Multiple myeloma