TY - JOUR
T1 - Effect of age and frailty on the efficacy and tolerability of once-weekly selinexor, bortezomib, and dexamethasone in previously treated multiple myeloma
AU - Auner, Holger W.
AU - Gavriatopoulou, Maria
AU - Delimpasi, Sosana
AU - Simonova, Maryana
AU - Spicka, Ivan
AU - Pour, Ludek
AU - Dimopoulos, Meletios A.
AU - Kriachok, Iryna
AU - Pylypenko, Halyna
AU - Leleu, Xavier
AU - Doronin, Vadim
AU - Usenko, Ganna
AU - Hajek, Roman
AU - Benjamin, Reuben
AU - Dolai, Tuphan Kanti
AU - Sinha, Dinesh Kumar
AU - Venner, Christopher P.
AU - Garg, Mamta
AU - Stevens, Don Ambrose
AU - Quach, Hang
AU - Jagannath, Sundar
AU - Moreau, Phillipe
AU - Levy, Moshe
AU - Badros, Ashraf
AU - Anderson, Larry D.
AU - Bahlis, Nizar J.
AU - Facon, Thierry
AU - Mateos, Maria Victoria
AU - Cavo, Michele
AU - Chai, Yi
AU - Arazy, Melina
AU - Shah, Jatin
AU - Shacham, Sharon
AU - Kauffman, Michael G.
AU - Richardson, Paul G.
AU - Grosicki, Sebastian
N1 - Publisher Copyright:
© 2021 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85104358050&partnerID=8YFLogxK
U2 - 10.1002/ajh.26172
DO - 10.1002/ajh.26172
M3 - Article
C2 - 33755235
AN - SCOPUS:85104358050
SN - 0361-8609
VL - 96
SP - 708
EP - 718
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 6
ER -