Contributions
Abstract: EP1002
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. XPO1 is required for multiple myeloma (MM) cell growth, is associated with poor prognosis and mediates resistance to standard MM therapies. Selinexor (SEL) is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound approved in combination with dexamethasone (dex) ± bortezomib for patients (pts) with previously treated MM. Once MM becomes refractory to anti-CD38 monoclonal antibodies (αCD38 mAb), pts have limited effective treatment options and poor prognoses. With standard therapies, overall response rate (ORR) to the first regimen after refractoriness to an αCD38 mAb is 31%, median progression-free survival (PFS) is 3.4 months and median overall survival (OS) is 8.6 months (Gandhi et al, Leukemia, 2019). The doublet SEL-dex (Xd) has shown ORR ~26% in triple-class (IMID, PI, αCD38 mAb) refractory MM and improved OS over matched cohorts in community (Richardson et al, eJHaem, 2021) and academic (Cornell et al, AJH, 2020) settings. SEL-based triplets could be more effective in this triple class treated population.
Aims
To retrospectively analyze the efficacy and safety of SEL-containing triplets in pts in the STOMP study previously treated with αCD38 mAbs.
Methods
STOMP is a multi-arm, open-label, Phase 1b/2 study evaluating SEL in various triplet combinations (ClinicalTrials.gov: NCT02343042). Pts who entered the study received Xd plus pomalidomide (XPd, n=19), bortezomib (XVd, n=4), lenalidomide (XRd, n=4), daratumumab (XDd, n=2) or carfilzomib (XKd, n=18). ORR, OS, PFS and adverse events (AEs) were analyzed.
Results
Among the 47 pts, median age 64 yrs, female 53%, median time from diagnosis 5.1 yrs, median number of prior regimens 5 (range, 2–11). Prior daratumumab (96%), isatuximab (4%); 96% had MM documented to be refractory to αCD38 mAb, 81% had triple-class refractory MM, 74% and 47% were quad- and penta-treated, 43% (20/47) and 15% (7/47) had quad- and penta-refractory MM. αCD38 mAb was included in the immediate prior regimen of 57% of pts and median duration from end of most recent αCD38 mAb therapy to first dose of study treatment was 6.9 weeks (range, 2.6-114.9). ORR was 51% among the 45 evaluable pts; 59% in the XPd arm (n=17; 2 pts were not efficacy evaluable) and 67% in the XKd arm. ORR was 47% (9/19) among efficacy evaluable pts with quad-refractory MM. Among all evaluable pts, median PFS was 8.8 months (95% CI: 4.9, NE) and median OS was 20.4 months (95% CI: 9.6, NE). Among the 25 pts with αCD38 mAb in their immediate prior regimen, efficacy of SEL-containing triplets was similar to that of the prior regimen: ORR 52% vs. 45%, median PFS 8.8 vs. 9.3 months. The most common treatment emergent AEs were nausea (72%), anemia (64%), thrombocytopenia (60%), fatigue (57%), which were managed with standard supportive care and dose modifications; cytopenias were infrequently symptomatic.
Conclusion
SEL-containing triplets in pts with MM previously treated with αCD38 mAbs, most of whom had triple-class refractory MM, exhibit tolerability and comparable effectiveness to their most recent αCD38 mAb-containing regimens. Compared to historical controls who received regimens with agents with which they were previously treated, OS on the SEL-containing triplets was much higher. These results suggest that the use of SEL-containing triplets can provide prolonged disease control with good tolerability rather than recycling previously utilized drugs/mechanisms. Further investigation is warranted.
Keyword(s): Clinical trial, Multiple myeloma
Abstract: EP1002
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. XPO1 is required for multiple myeloma (MM) cell growth, is associated with poor prognosis and mediates resistance to standard MM therapies. Selinexor (SEL) is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound approved in combination with dexamethasone (dex) ± bortezomib for patients (pts) with previously treated MM. Once MM becomes refractory to anti-CD38 monoclonal antibodies (αCD38 mAb), pts have limited effective treatment options and poor prognoses. With standard therapies, overall response rate (ORR) to the first regimen after refractoriness to an αCD38 mAb is 31%, median progression-free survival (PFS) is 3.4 months and median overall survival (OS) is 8.6 months (Gandhi et al, Leukemia, 2019). The doublet SEL-dex (Xd) has shown ORR ~26% in triple-class (IMID, PI, αCD38 mAb) refractory MM and improved OS over matched cohorts in community (Richardson et al, eJHaem, 2021) and academic (Cornell et al, AJH, 2020) settings. SEL-based triplets could be more effective in this triple class treated population.
Aims
To retrospectively analyze the efficacy and safety of SEL-containing triplets in pts in the STOMP study previously treated with αCD38 mAbs.
Methods
STOMP is a multi-arm, open-label, Phase 1b/2 study evaluating SEL in various triplet combinations (ClinicalTrials.gov: NCT02343042). Pts who entered the study received Xd plus pomalidomide (XPd, n=19), bortezomib (XVd, n=4), lenalidomide (XRd, n=4), daratumumab (XDd, n=2) or carfilzomib (XKd, n=18). ORR, OS, PFS and adverse events (AEs) were analyzed.
Results
Among the 47 pts, median age 64 yrs, female 53%, median time from diagnosis 5.1 yrs, median number of prior regimens 5 (range, 2–11). Prior daratumumab (96%), isatuximab (4%); 96% had MM documented to be refractory to αCD38 mAb, 81% had triple-class refractory MM, 74% and 47% were quad- and penta-treated, 43% (20/47) and 15% (7/47) had quad- and penta-refractory MM. αCD38 mAb was included in the immediate prior regimen of 57% of pts and median duration from end of most recent αCD38 mAb therapy to first dose of study treatment was 6.9 weeks (range, 2.6-114.9). ORR was 51% among the 45 evaluable pts; 59% in the XPd arm (n=17; 2 pts were not efficacy evaluable) and 67% in the XKd arm. ORR was 47% (9/19) among efficacy evaluable pts with quad-refractory MM. Among all evaluable pts, median PFS was 8.8 months (95% CI: 4.9, NE) and median OS was 20.4 months (95% CI: 9.6, NE). Among the 25 pts with αCD38 mAb in their immediate prior regimen, efficacy of SEL-containing triplets was similar to that of the prior regimen: ORR 52% vs. 45%, median PFS 8.8 vs. 9.3 months. The most common treatment emergent AEs were nausea (72%), anemia (64%), thrombocytopenia (60%), fatigue (57%), which were managed with standard supportive care and dose modifications; cytopenias were infrequently symptomatic.
Conclusion
SEL-containing triplets in pts with MM previously treated with αCD38 mAbs, most of whom had triple-class refractory MM, exhibit tolerability and comparable effectiveness to their most recent αCD38 mAb-containing regimens. Compared to historical controls who received regimens with agents with which they were previously treated, OS on the SEL-containing triplets was much higher. These results suggest that the use of SEL-containing triplets can provide prolonged disease control with good tolerability rather than recycling previously utilized drugs/mechanisms. Further investigation is warranted.
Keyword(s): Clinical trial, Multiple myeloma