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    Clinical features and survival outcomes in IgD myeloma: a study by Asia Myeloma Network (AMN)

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    Author
    Liu, Jin
    Hu, Xiaoxia
    Jia, Yanchun
    Lu, Jin
    Lee, Jae Hoon
    Kim, Kihyun
    Chen, Wenming
    Liu, Aijun
    Liu, Yang
    Chen, Qi
    Zhang, Chunyang
    Suh, Cheolwon
    Kim, Min Kyoung
    Zhou, Fan
    Chng, Wee Joo
    Kumar, Shaji K
    Durie, Brian
    Hou, Jian
    Fu, Weijun
    Du, Juan
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    Date
    2020-10-20
    Journal
    Leukemia
    Publisher
    Springer Nature
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1038/s41375-020-01060-w
    Sponsors
    National Natural Science Foundation of China
    Keyword
    IgD myeloma
    immunoglobulin D myeloma
    Asian Myeloma Network (AMN)
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/13965
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41375-020-01060-w
    Scopus Count
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    UMB Open Access Articles 2020

    entitlement

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    • Thumbnail

      Utilization of novel systemic therapies for multiple myeloma: A retrospective study of front-line regimens using the SEER-Medicare data

      Khairnar, R.; Yared, J.A.; Onukwugha, E.; Slejko, J.F. (John Wiley & Sons Ltd., 2019)
      The landscape of treatment for multiple myeloma (MM) has significantly changed over the last decade due to novel agents that have shown superiority in efficacy such as proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) over traditional therapies. However, the real-world utilization of these new agents has not been studied well. This study evaluated year-to-year changes in treatment choices in a cohort of patients aged 66 or older in the Surveillance, Epidemiology, and End Results (SEER) registry linked with Medicare claims (SEER-Medicare) data who were diagnosed with MM between 2007 and 2011. We identified 2477 symptomatic newly diagnosed patients who were followed for 6 months or more postdiagnosis and treated with systemic therapies but not with stem cell transplantation. Symptomatic patients were identified by evidence of hypercalcemia, renal failure, anemia, or bone lesions (CRAB criteria). The minimum follow-up was imposed to ensure sufficient data to characterize treatment. Our analysis found that the proportion of treated patients increased from 75% in the 2007 cohort to 79% in the 2011 cohort. The share of PI-based regimens including PI plus alkylating agents, PI plus IMiD, and PI-only increased from 9% to 21%, 3% to 11%, and 16% to 22%, respectively, between 2007 and 2011. These findings translate to the share of PI-based regimens having increased from 28% to 55% and that of IMiDs-based regimens (excluding PI plus IMiD) having decreased from 43% to 27%. In conclusion, while the usage of PIs among elderly MM patients increased significantly replacing IMiD-based regimens (with or without alkylating agents but not with PI) between 2007 and 2011, this significant shift did not increase the proportion of treated patients. Copyright 2019 The Authors.
    • Thumbnail

      A phase 1 clinical trial evaluating marizomib, pomalidomide and low-dose dexamethasone in relapsed and refractory multiple myeloma (NPI-0052-107): final study results

      Spencer, A.; Harrison, S.; Zonder, J. (Blackwell Publishing Ltd, 2018)
      Marizomib (MRZ) is an irreversible, pan‐subunit proteasome inhibitor (PI) in clinical development for relapsed/refractory multiple myeloma (RRMM) and glioma. This study analysed MRZ, pomalidomide (POM) and low‐dose dexamethasone (Lo‐DEX) [PMD] in RRMM to evaluate safety and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Intravenous MRZ (0·3–0·5 mg/m2) was administered over 2 h on days 1, 4, 8, 11; POM (3–4 mg) on days 1–21; and Lo‐DEX (5 or 10 mg) on days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22 and 23 of every 28‐day cycle. Thirty‐eight patients were enrolled that had received a median of 4 (range 1–10) prior lines of therapy; all patients received prior lenalidomide and bortezomib. No dose‐limiting toxicities (DLTs) were observed and 0·5 mg/m2 MRZ was determined to be the RP2D. The most common treatment‐related ≥Grade 3 adverse events were: neutropenia (11/38 patients: 29%), pneumonia (4/38 patients 11%), anaemia (4/38 patients; 11%) and thrombocytopenia (4/38 patients; 11%). The overall response rate and clinical benefit rate was 53% (19/36) and 64% (23/36), respectively. In conclusion, PMD was well tolerated and demonstrated promising activity in heavily pre‐treated, high‐risk RRMM patients. Copyright 2017 John Wiley & Sons Ltd.
    • Thumbnail

      Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody–Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study

      Farooq, Asim V.; Degli Esposti, Simona; Popat, Rakesh; Thulasi, Praneetha; Lonial, Sagar; Nooka, Ajay K.; Jakubowiak, Andrzej; Sborov, Douglas; Zaugg, Brian E.; Badros, Ashraf Z.; et al. (Springer Science and Business Media LLC, 2020-07-25)
      Introduction: Patients with relapsed or refractory multiple myeloma (RRMM) represent an unmet clinical need. Belantamab mafodotin (belamaf; GSK2857916) is a first-in-class antibody–drug conjugate (ADC; or immunoconjugate) that delivers a cytotoxic payload, monomethyl auristatin F (MMAF), to myeloma cells. In the phase II DREAMM-2 study (NCT03525678), single-agent belamaf (2.5 mg/kg) demonstrated clinically meaningful anti-myeloma activity (overall response rate 32%) in patients with heavily pretreated disease. Microcyst-like epithelial changes (MECs) were common, consistent with reports from other MMAF-containing ADCs. Methods: Corneal examination findings from patients in DREAMM-2 were reviewed, and the clinical descriptions and accompanying images (slit lamp microscopy and in vivo confocal microscopy [IVCM]) of representative events were selected. A literature review on corneal events reported with other ADCs was performed. Results: In most patients receiving single-agent belamaf (72%; 68/95), MECs were observed by slit lamp microscopy early in treatment (69% had their first event by dose 4). However, IVCM revealed hyperreflective material. Blurred vision (25%) and dry eye (15%) were commonly reported symptoms. Management of MECs included dose delays (47%)/reductions (25%), with few patients discontinuing due to MECs (1%). The first event resolved in most patients (grade ≥2 MECs and visual acuity[each 77%], blurred vision [67%], and dry eye [86%]), with no reports of permanent vision loss to date. A literature review confirmed that similar MECs were reported with other ADCs; however, event management strategies varied. The pathophysiology of MECs is unclear, though the ADC cytotoxic payload may contribute to on- or off-target effects on corneal epithelial cells. Conclusion: Single-agent belamaf represents a new treatment option for patients with RRMM. As with other ADCs, MECs were observed and additional research is warranted to determine their pathophysiology. A multidisciplinary approach, involving close collaboration between eye care professionals and hematologist/oncologists, is needed to determine appropriate diagnosis and management of these patients. Trial Registration: ClinicalTrials.gov Identifier, NCT03525678. © 2020, The Author(s).
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