Contributions
Abstract: EP974
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Lenalidomide (LEN) is typically a frontline therapy for newly diagnosed MM. Patients (pts) with MM refractory to LEN are less likely to respond to other IMiDs and represent a signification area of unmet medical need. In the ITT population of the BOSTON study, selinexor, bortezomib, and dexamethasone (XVd) was associated with significant improvements in median progression-free survival (PFS), overall response rate (ORR), and rates of peripheral neuropathy, with trends in overall survival (OS) favoring XVd.
Aims
This study aimed to evaluate if PFS, overall response rate (ORR), time to next treatment (TTNT) and tolerability were influenced by prior treatment with LEN when comparing XVd with Vd.
Methods
The BOSTON trial (NCT03110562) is a Phase 3 randomized, controlled, open-label study of once weekly XVd vs twice weekly bortezomib and dexamethasone (Vd) in pts with MM and 1-3 prior therapies. We performed post-hoc analyses on two different subgroups to compare outcomes based on refractory status to LEN and immunomodulatory drug (IMiD) therapy.
Results
Amongst the 402 pts in BOSTON, 160 had MM refractory to any IMiD (XVd=74, Vd=86). Of those, 106 were documented to be refractory to LEN (XVd=53, Vd=53) and 296 were not refractory to LEN (XVd=142, Vd=154). Baseline characteristics were generally well balanced between subgroups. In these subgroups based on refractory status to IMiD or LEN, median PFS was significantly longer in the XVd arm as compared to Vd (IMiD refractory: 13.9 vs. 8.4 months (mo), p=0.005; LEN refractory: 10.2 vs. 7.1 mo, p=0.012; not LEN refractory, 15.4 vs 9.6 mo, p=0.014). Significant increases in TTNT were observed with XVd treatment in pts with MM that was: IMiD refractory (14.8 vs. 10.2 mo, p=0.003), LEN refractory (13.0 vs. 7.6 mo, p=0.015), and LEN not refractory (19.1 vs 12.9 mo, p=0.005). ORR was improved with XVd compared to Vd regardless of refractory status (IMiD refractory: 68.9% vs 55.8%, p=0.045; LEN refractory: 67.9% vs. 47.2%, p=0.016; and LEN not refractory: 79.6% vs 67.5%, p=0.010). The most common treatment-emergent AEs for the XVd/Vd arms for all subgroups were thrombocytopenia (66.2/30.6%; 71.7/40.4%; 55.6/22.4%), nausea (48.6/11.8%; 50.9/11.5%; 50.0/9.2%) and fatigue (40.5/20.0%; 45.3/21.2%; 40.8/17.1%) for IMiD, LEN, and not LEN refractory, respectively. Incidence of PN AEs of any grade were reduced with XVd compared to Vd: IMiD refractory: 27% vs. 42.4%; LEN refractory: 30.2% vs 36.5%; LEN not refractory: 33.1% vs 50.7%.
Conclusion
In pts with previously treated MM, PFS, ORR, and TTNT were significantly improved regardless of documented refractory status to LEN or to any IMiD. These analyses support the use of the XVd combination for pts with disease refractory to LEN and likely to any IMiD.
Keyword(s): Clinical trial, Multiple myeloma
Abstract: EP974
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Lenalidomide (LEN) is typically a frontline therapy for newly diagnosed MM. Patients (pts) with MM refractory to LEN are less likely to respond to other IMiDs and represent a signification area of unmet medical need. In the ITT population of the BOSTON study, selinexor, bortezomib, and dexamethasone (XVd) was associated with significant improvements in median progression-free survival (PFS), overall response rate (ORR), and rates of peripheral neuropathy, with trends in overall survival (OS) favoring XVd.
Aims
This study aimed to evaluate if PFS, overall response rate (ORR), time to next treatment (TTNT) and tolerability were influenced by prior treatment with LEN when comparing XVd with Vd.
Methods
The BOSTON trial (NCT03110562) is a Phase 3 randomized, controlled, open-label study of once weekly XVd vs twice weekly bortezomib and dexamethasone (Vd) in pts with MM and 1-3 prior therapies. We performed post-hoc analyses on two different subgroups to compare outcomes based on refractory status to LEN and immunomodulatory drug (IMiD) therapy.
Results
Amongst the 402 pts in BOSTON, 160 had MM refractory to any IMiD (XVd=74, Vd=86). Of those, 106 were documented to be refractory to LEN (XVd=53, Vd=53) and 296 were not refractory to LEN (XVd=142, Vd=154). Baseline characteristics were generally well balanced between subgroups. In these subgroups based on refractory status to IMiD or LEN, median PFS was significantly longer in the XVd arm as compared to Vd (IMiD refractory: 13.9 vs. 8.4 months (mo), p=0.005; LEN refractory: 10.2 vs. 7.1 mo, p=0.012; not LEN refractory, 15.4 vs 9.6 mo, p=0.014). Significant increases in TTNT were observed with XVd treatment in pts with MM that was: IMiD refractory (14.8 vs. 10.2 mo, p=0.003), LEN refractory (13.0 vs. 7.6 mo, p=0.015), and LEN not refractory (19.1 vs 12.9 mo, p=0.005). ORR was improved with XVd compared to Vd regardless of refractory status (IMiD refractory: 68.9% vs 55.8%, p=0.045; LEN refractory: 67.9% vs. 47.2%, p=0.016; and LEN not refractory: 79.6% vs 67.5%, p=0.010). The most common treatment-emergent AEs for the XVd/Vd arms for all subgroups were thrombocytopenia (66.2/30.6%; 71.7/40.4%; 55.6/22.4%), nausea (48.6/11.8%; 50.9/11.5%; 50.0/9.2%) and fatigue (40.5/20.0%; 45.3/21.2%; 40.8/17.1%) for IMiD, LEN, and not LEN refractory, respectively. Incidence of PN AEs of any grade were reduced with XVd compared to Vd: IMiD refractory: 27% vs. 42.4%; LEN refractory: 30.2% vs 36.5%; LEN not refractory: 33.1% vs 50.7%.
Conclusion
In pts with previously treated MM, PFS, ORR, and TTNT were significantly improved regardless of documented refractory status to LEN or to any IMiD. These analyses support the use of the XVd combination for pts with disease refractory to LEN and likely to any IMiD.
Keyword(s): Clinical trial, Multiple myeloma