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    Effect of Age and Frailty on the Efficacy and Tolerability of Once-Weekly Selinexor, Bortezomib, and Dexamethasone in Previously Treated Multiple Myeloma

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    Author
    Auner, Holger W
    Gavriatopoulou, Maria
    Delimpasi, Sosana
    Simonova, Maryana
    Spicka, Ivan
    Pour, Ludek
    Dimopoulos, Meletios A
    Kriachok, Iryna
    Pylypenko, Halyna
    Leleu, Xavier
    Doronin, Vadim
    Usenko, Ganna
    Hajek, Roman
    Benjamin, Reuben
    Dolai, Tuphan Kanti
    Sinha, Dinesh Kumar
    Venner, Christopher P
    Garg, Mamta
    Stevens, Don Ambrose
    Quach, Hang
    Jagannath, Sundar
    Moreau, Phillipe
    Levy, Moshe
    Badros, Ashraf
    Anderson, Larry D
    Bahlis, Nizar J
    Facon, Thierry
    Mateos, Maria Victoria
    Cavo, Michele
    Chai, Yi
    Arazy, Melina
    Shah, Jatin
    Shacham, Sharon
    Kauffman, Michael G
    Richardson, Paul G
    Grosicki, Sebastian
    Show allShow less

    Date
    2021-03-23
    Journal
    American Journal of Hematology
    Publisher
    Wiley-Blackwell
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1002/ajh.26172
    Abstract
    Elderly and frail patients with multiple myeloma (MM) are more vulnerable to the toxicity of combination therapies, often resulting in treatment modifications and suboptimal outcomes. The phase 3 BOSTON study showed that once-weekly selinexor and bortezomib with low-dose dexamethasone (XVd) improved PFS and ORR compared with standard twice-weekly bortezomib and moderate-dose dexamethasone (Vd) in patients with previously treated MM. This is a retrospective subgroup analysis of the multicenter, prospective, randomized BOSTON trial. Post hoc analyses were performed to compare XVd versus Vd safety and efficacy according to age and frailty status (<65 and ≥65 years, nonfrail and frail). Patients ≥65 years with XVd had higher ORR (OR 1.77, p =.024), ≥VGPR (OR, 1.68, p =.027), PFS (HR 0.55, p =.002), and improved OS (HR 0.63, p =.030), compared with Vd. In frail patients, XVd was associated with a trend towards better PFS (HR 0.69, p =.08) and OS (HR 0.62, p =.062). Significant improvements were also observed in patients <65 (ORR and TTNT) and nonfrail patients (PFS, ORR, ≥VGPR, and TTNT). Patients treated with XVd had a lower incidence of grade ≥ 2 peripheral neuropathy in ≥65 year-old (22% vs. 37%; p =.0060) and frail patients (15% vs. 44%; p =.0002). Grade ≥3 TEAEs were not observed more often in older compared to younger patients, nor in frail compared to nonfrail patients. XVd is safe and effective in patients <65 and ≥65 and in nonfrail and frail patients with previously treated MM. © 2021 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.
    Keyword
    multiple myeloma
    frailty
    bortezomid
    clinical trial
    selinexor
    exportin
    karyopherins
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/15536
    ae974a485f413a2113503eed53cd6c53
    10.1002/ajh.26172
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