Contributions
Abstract: EP924
Type: E-Poster Presentation
Session title: Myelodysplastic syndromes - Clinical
Background
Patients (pts) with myelodysplastic syndrome (MDS) refractory to hypomethylating agents (HMAs) have limited therapeutic options and a dismal prognosis with a median overall survival (mOS) of 4-6 months. Eltanexor (ELTA) is a second-generation, oral, selective inhibitor of nuclear export (SINE) compound that showed anti-tumor activity and lower brain penetration compared to selinexor (SEL) in nonclinical models. It was hypothesized that ELTA could be dosed more frequently than SEL with a lower incidence of centrally mediated nausea. Early results from a phase 1/2 study of ELTA in pts with HMA refractory MDS demonstrated marrow complete responses (mCRs) and stable disease (SD); side effects were primarily low-grade, dose-dependent, and reversible (Lee ASH 2019).
Aims
In this abstract, we provide a subgroup analysis of and update on mOS in the efficacy evaluable population.
Methods
This phase 1/2 study (NCT02649790) evaluated single-agent oral ELTA in pts with higher-risk MDS, ie, high-risk or intermediate-2 MDS by International Prognostic Scoring System (IPSS) and 5%>19% myeloblasts. Of 20 pts enrolled, 15 pts were evaluable for efficacy and constitute the population studied in this analysis. Two doses of ELTA were evaluated: 10 mg (n=5) or 20 mg (n=15) every day for 5 days per week of a 28-day cycle.
Results
As of 1 Feb 2021, the 15 pts evaluable for efficacy (median age 76 years; range 62-89) had a median of 2 prior treatment regimens (range 1-4); 14 pts (93%) had higher-risk MDS including 9 pts (60%) high risk and 5 pts (33%) int-2. Similarly, using the global MD Anderson Cancer Center (MDACC) risk prognosis model (Kantarjian 2008), 14 pts (93%) had higher-risk MDS with 2 pts (13%) high risk and 12 pts (80%) int-2. Of the 20 enrolled patients, 7 (35%) had mCR and 5 (25%) had SD for a total disease control (mCR+SD) rate of 60%. Of the 15 pts evaluable for efficacy, 7 (47%) had mCR and 5 (33%) had SD. In the 10-mg cohort (n=5), all pts derived clinical benefit with 3 pts (60%) reaching mCR and 2 pts (40%) SD. In the 20-mg cohort (n=10), 4 pts (40%) had mCR and 3 (30%) had SD. Four pts had hematologic improvement (HI) and became transfusion independent for at least 8 weeks including 2 pts with tri-lineage HI. OS for pts who reached mCR (n=7) was significantly longer than for pts who did not reach mCR (n=8): median 11.86 vs 8.67 months (mo) (hazard ratio [HR]=0.27, p=0.05), and significantly longer than OS for pts with PD (n=3, mOS=3.15 mo, HR=0.23, p=0.04). Pts with disease control (n=12) had numerically longer mOS than pts with PD (9.86 vs 3.15 mo, HR=0.38, p=0.09). Pts with HI had a mOS of 10.58 months.
Conclusion
Single-agent oral ELTA was active in pts with high-risk, HMA-refractory MDS. Pts with mCR had significantly longer mOS than pts without mCR or with PD. Given the limited prognostic power of IPSS in HMA refractory pts, the MDACC model was also applied here for improved risk assessment. Further evaluation of ELTA in MDS as a single agent and in combination with other agents is ongoing.
Keyword(s): Hypomethylation, Myelodysplasia, Refractory
Abstract: EP924
Type: E-Poster Presentation
Session title: Myelodysplastic syndromes - Clinical
Background
Patients (pts) with myelodysplastic syndrome (MDS) refractory to hypomethylating agents (HMAs) have limited therapeutic options and a dismal prognosis with a median overall survival (mOS) of 4-6 months. Eltanexor (ELTA) is a second-generation, oral, selective inhibitor of nuclear export (SINE) compound that showed anti-tumor activity and lower brain penetration compared to selinexor (SEL) in nonclinical models. It was hypothesized that ELTA could be dosed more frequently than SEL with a lower incidence of centrally mediated nausea. Early results from a phase 1/2 study of ELTA in pts with HMA refractory MDS demonstrated marrow complete responses (mCRs) and stable disease (SD); side effects were primarily low-grade, dose-dependent, and reversible (Lee ASH 2019).
Aims
In this abstract, we provide a subgroup analysis of and update on mOS in the efficacy evaluable population.
Methods
This phase 1/2 study (NCT02649790) evaluated single-agent oral ELTA in pts with higher-risk MDS, ie, high-risk or intermediate-2 MDS by International Prognostic Scoring System (IPSS) and 5%>19% myeloblasts. Of 20 pts enrolled, 15 pts were evaluable for efficacy and constitute the population studied in this analysis. Two doses of ELTA were evaluated: 10 mg (n=5) or 20 mg (n=15) every day for 5 days per week of a 28-day cycle.
Results
As of 1 Feb 2021, the 15 pts evaluable for efficacy (median age 76 years; range 62-89) had a median of 2 prior treatment regimens (range 1-4); 14 pts (93%) had higher-risk MDS including 9 pts (60%) high risk and 5 pts (33%) int-2. Similarly, using the global MD Anderson Cancer Center (MDACC) risk prognosis model (Kantarjian 2008), 14 pts (93%) had higher-risk MDS with 2 pts (13%) high risk and 12 pts (80%) int-2. Of the 20 enrolled patients, 7 (35%) had mCR and 5 (25%) had SD for a total disease control (mCR+SD) rate of 60%. Of the 15 pts evaluable for efficacy, 7 (47%) had mCR and 5 (33%) had SD. In the 10-mg cohort (n=5), all pts derived clinical benefit with 3 pts (60%) reaching mCR and 2 pts (40%) SD. In the 20-mg cohort (n=10), 4 pts (40%) had mCR and 3 (30%) had SD. Four pts had hematologic improvement (HI) and became transfusion independent for at least 8 weeks including 2 pts with tri-lineage HI. OS for pts who reached mCR (n=7) was significantly longer than for pts who did not reach mCR (n=8): median 11.86 vs 8.67 months (mo) (hazard ratio [HR]=0.27, p=0.05), and significantly longer than OS for pts with PD (n=3, mOS=3.15 mo, HR=0.23, p=0.04). Pts with disease control (n=12) had numerically longer mOS than pts with PD (9.86 vs 3.15 mo, HR=0.38, p=0.09). Pts with HI had a mOS of 10.58 months.
Conclusion
Single-agent oral ELTA was active in pts with high-risk, HMA-refractory MDS. Pts with mCR had significantly longer mOS than pts without mCR or with PD. Given the limited prognostic power of IPSS in HMA refractory pts, the MDACC model was also applied here for improved risk assessment. Further evaluation of ELTA in MDS as a single agent and in combination with other agents is ongoing.
Keyword(s): Hypomethylation, Myelodysplasia, Refractory