Imetelstat improves red blood cell transfusion independence rates vs placebo in patients with lower-risk myelodysplastic syndromes (MDS) relapsed/refractory to erythropoiesis-stimulating agents across different subgroups, according to data from the IMerge phase 3 study presented at the 2023 ASH Annual Meeting.

Previous results from this study reported higher rates of ≥8-week, ≥24-week and 1-year red blood cell transfusion independence with imetelstat than with placebo. This updated analysis, presented by Rami Komrokji, MD, Moffitt Cancer Center, Tampa, Florida, examined the clinical efficacy of imetelstat across different International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R), IPSS-R cytogenetic, or IPSS-molecular (IPSS-M) risk categories. 

Researchers performed cytogenetic analysis centrally on bone marrow aspirates by karyotyping and analyzed mutation profile using peripheral blood samples by next generation sequencing (NGS). The NGS panel consisted of 36 genes commonly mutated in MDS.

Baseline IPSS, IPSS-R, IPSS-R cytogenetic, or IPSS-M risk categories were derived for patients in the phase 3 portion of IMerge based on specific classification criteria, and rates of RBC-TI ≥8-week, ≥24-week, ≥1-year were assessed for each risk subgroup.

Among 105 patients considered IPSS-low, 95 (90.5%) remained IPSS-M very low/low/moderate low and 10 patients (9.5%) upstaged to IPSS-M moderate high and high. Among 50 patients considered IPSS-intermediate-1, 39 (78%) remained IPSS-M very low/low/moderate low and 11 patients (22%) upstaged to IPSS-M moderate high/high. Among 129 patients considered IPSS-R low/very low, 118 (91.5%) remained IPSS-M very low/low/moderate low and 11 (8.5%) patients upstaged to IPSS-moderate high/high. Among 25 patients considered IPSS-R–intermediate, 16 (64%) remained IPSS-M low/moderate low and 9 patients (36%) upstaged to IPSS-M moderate high/high/very high. One IPSS-R high-risk patient remained IPSS-M high.

Consistent with previous reports, imetelstat yielded significantly higher rates of ≥8-week, ≥24-week, and ≥1-year red blood cell transfusion independence (39.8%, 28%, and 13.6%, respectively) vs placebo (15%, 3.3%, and 1.7%). Imetelstat also demonstrated higher transfusion independent response rates vs placebo across different risk subgroups, regardless of classification system.

For IPSS risk groups, the ≥8-week, ≥24-week, and ≥1-year transfusion independence rates in low-risk patients with imetelstat vs placebo were 40% vs 20.5% (P = .034), 28.8% vs 5.1% (P = .003), and 12.5% vs 2.6% (P = .082), respectively. In patients with intermediate-1 risk, these were 39.5% vs 4.8% (P = .004), 26.3% vs 0% (P = .009), and 15.8% vs 0% (P = .048), respectively.

For IPSS-R risk groups, the ≥8-week, ≥24-week, and ≥1-year transfusion independence rates in low-risk patients with imetelstat vs placebo were 42.5% vs 19.6%, 29.9% vs 4.3%, and 11.5% vs 2.2%, respectively. In the intermediate-risk subgroup, the ≥8-week, ≥24-week, ≥1-year transfusion independence rates with imetelstat were 35%, 25%, and 20%, respectively, and placebo exhibited no response. There were not enough patients in the very low or high IPSS-R subgroups to be evaluable for transfusion independence.

For IPSS-R cytogenetic risk groups, the ≥8-week, ≥24-week, and ≥1-year transfusion independence rates in very good/good risk groups with imetelstat vs placebo were 37.1% vs 17%, 24.7% vs 4.3%, and 10.1% vs 2.1%, respectively. In the intermediate-risk group, these were 54.5% vs 11.1%, 40.9% vs 0%, and 22.7% vs 0%, respectively.

For IPSS-M risk groups, the ≥8-week, ≥24-week, and ≥1-year transfusion independence rates in the very low/low risk subgroup with imetelstat vs placebo were 47.8% vs 21.2%, 34.8% vs 3%, and 14.5% vs 0%, respectively. In patients with moderate low/moderate risk, these were 20.7% vs 6.3%, 10.3% vs 0%, and 6.9% vs 0%, respectively. In patients with high/very high risk, the ≥8-week transfusion independence rates were 40% vs 0%, with no ≥24-week or ≥1-year transfusion independence reported for either arm. 

Dr Komrokji and colleagues highlighted that “placebo had not achieved durable (≥24-week and ≥1-year) TI [transfusion independence] response in the higher-risk groups irrespective of the risk classification assessment model used, while TI response rates with imetelstat in higher-risk subgroups with poor prognosis were similar to TI response rates in lower-risk subgroups… indicating that clinical efficacy of imetelstat is independent of risk categories.”

Source:

Komrokji RS, Santini V, Fenaux P, et al. Efficacy of Imetelstat in Achieving Red Blood Cell Transfusion Independence (RBC-TI) across Different Risk Subgroups in Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS) Relapsed/Refractory (R/R) to Erythropoiesis-Stimulating Agents (ESAs) in IMerge Phase 3 Study; December 9-12, 2023; San Diego, CA. Abstract 194.