Contributions
Abstract: EP1008
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Exportin 1 (XPO1) mediates the nuclear export and functional inactivation of tumor suppressor proteins (TSPs), is associated with poor prognosis in MM, and contributes to proteasome inhibitor (PI) and immunomodulatory drug (IMiD) resistance. Selinexor (SEL) is a novel, oral, first-in-class selective inhibitor of nuclear export (SINE) compound that blocks XPO1, forcing the nuclear retention and activation of TSPs. SEL is approved with low-dose dexamethasone (dex) ± bortezomib (BOR) for patients (pts) with previously treated MM. In the Phase 3 BOSTON study, once weekly (QW) SEL, QW BOR, and dex (XVd) significantly increased progression-free survival (PFS) and overall response rate (ORR) with marked reduction of peripheral neuropathy as compared to standard twice weekly BOR/dex (Vd), despite XVd utilizing 40% less BOR and 25% less dex than Vd. Pomalidomide (POM) plus dex (Pd) has an ORR of 31% and median PFS (mPFS) of 4 months in MM pts refractory to BOR and lenalidomide (LEN).
Aims
To determine if the addition of once weekly SEL to Pd (XPd) would be an active, all-oral combination with an acceptable safety profile in pts with LEN- and BOR-treated MM.
Methods
In the XPd arm of the multi-arm Phase 1b/2 STOMP study, SEL was evaluated at 60, 80, or 100 mg QW or 60 or 80 mg twice weekly in combination with Pd. Study objectives were to determine the maximum tolerated dose and recommended Phase 2 dose (RP2D) and to assess the safety and activity of the XPd regimen overall and at the RP2D.
Results
As of 4 Jan 2021, 65 pts (33 male) were enrolled with median age of 64 years (range 37-85 years) and median of 3 (range 1-10) prior lines of therapy. Previously treated/refractory rates were LEN 100%/85%, BOR 92%/49%, carfilzomib 43%/37%, POM 31%/29%, and daratumumab (dara) 26%/26%. RP2D was SEL 60 mg QW, POM 4 mg (days 1-21), dex 40 mg QW.
Common hematologic, treatment-related adverse events (TRAEs) included (all grades, grades ≥3) neutropenia (63%, 55%), anemia (58%, 32%), and thrombocytopenia (54%, 31%) which were typically asymptomatic. Non-hematologic TRAEs were reversible and included nausea (62%, 2%), fatigue (55%, 11%), and decreased appetite (45%, 2%).
Among pts with POM naïve or nonrefractory MM (N=44), ORR was 57% (1 sCR, 1 CR, 8 VGPR, 15 PR); mPFS was 12.2 months. In pts treated with RP2D (N=20), ORR was 65% (1 sCR, 5 VGPR, 7 PR); mPFS was not reached with a median follow-up time of 3.9 months. In pts with POM-refractory MM and those with prior dara, ORRs were 44% (7/16) and 60% (9/15), respectively.
Conclusion
SEL, once weekly, can be safely combined with Pd in pts with heavily pretreated MM. No new safety signals were identified. The all-oral combination of XPd is highly active with an ORR of 65% at RP2D (compared to expected ORR ~30% for Pd) and produces durable responses with a mPFS of 12.2 months overall. These data support a planned Phase 3 study with an all-oral combination of XPd vs elotuzumab-Pd in pts who have been previously treated with LEN, a PI, and an anti-CD38 mAb.
Keyword(s): Multiple myeloma, Refractory, Relapse
Abstract: EP1008
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Exportin 1 (XPO1) mediates the nuclear export and functional inactivation of tumor suppressor proteins (TSPs), is associated with poor prognosis in MM, and contributes to proteasome inhibitor (PI) and immunomodulatory drug (IMiD) resistance. Selinexor (SEL) is a novel, oral, first-in-class selective inhibitor of nuclear export (SINE) compound that blocks XPO1, forcing the nuclear retention and activation of TSPs. SEL is approved with low-dose dexamethasone (dex) ± bortezomib (BOR) for patients (pts) with previously treated MM. In the Phase 3 BOSTON study, once weekly (QW) SEL, QW BOR, and dex (XVd) significantly increased progression-free survival (PFS) and overall response rate (ORR) with marked reduction of peripheral neuropathy as compared to standard twice weekly BOR/dex (Vd), despite XVd utilizing 40% less BOR and 25% less dex than Vd. Pomalidomide (POM) plus dex (Pd) has an ORR of 31% and median PFS (mPFS) of 4 months in MM pts refractory to BOR and lenalidomide (LEN).
Aims
To determine if the addition of once weekly SEL to Pd (XPd) would be an active, all-oral combination with an acceptable safety profile in pts with LEN- and BOR-treated MM.
Methods
In the XPd arm of the multi-arm Phase 1b/2 STOMP study, SEL was evaluated at 60, 80, or 100 mg QW or 60 or 80 mg twice weekly in combination with Pd. Study objectives were to determine the maximum tolerated dose and recommended Phase 2 dose (RP2D) and to assess the safety and activity of the XPd regimen overall and at the RP2D.
Results
As of 4 Jan 2021, 65 pts (33 male) were enrolled with median age of 64 years (range 37-85 years) and median of 3 (range 1-10) prior lines of therapy. Previously treated/refractory rates were LEN 100%/85%, BOR 92%/49%, carfilzomib 43%/37%, POM 31%/29%, and daratumumab (dara) 26%/26%. RP2D was SEL 60 mg QW, POM 4 mg (days 1-21), dex 40 mg QW.
Common hematologic, treatment-related adverse events (TRAEs) included (all grades, grades ≥3) neutropenia (63%, 55%), anemia (58%, 32%), and thrombocytopenia (54%, 31%) which were typically asymptomatic. Non-hematologic TRAEs were reversible and included nausea (62%, 2%), fatigue (55%, 11%), and decreased appetite (45%, 2%).
Among pts with POM naïve or nonrefractory MM (N=44), ORR was 57% (1 sCR, 1 CR, 8 VGPR, 15 PR); mPFS was 12.2 months. In pts treated with RP2D (N=20), ORR was 65% (1 sCR, 5 VGPR, 7 PR); mPFS was not reached with a median follow-up time of 3.9 months. In pts with POM-refractory MM and those with prior dara, ORRs were 44% (7/16) and 60% (9/15), respectively.
Conclusion
SEL, once weekly, can be safely combined with Pd in pts with heavily pretreated MM. No new safety signals were identified. The all-oral combination of XPd is highly active with an ORR of 65% at RP2D (compared to expected ORR ~30% for Pd) and produces durable responses with a mPFS of 12.2 months overall. These data support a planned Phase 3 study with an all-oral combination of XPd vs elotuzumab-Pd in pts who have been previously treated with LEN, a PI, and an anti-CD38 mAb.
Keyword(s): Multiple myeloma, Refractory, Relapse