P732: analysis of patient-reported fatigue in imerge ph3 trial of imetelstat vs placebo in heavily transfused non-del(5q) lower-risk myelodysplastic syndromes r/r to erythropoiesis stimulating agents

Background: Patients (pts) with lower risk myelodysplastic syndromes (LR-MDS) and anemia experience severe fatigue that negatively impacts overall functioning and daily life. Fatigue can also be commonly reported with treatments for LR-MDS, the goals of which are to minimize transfusions and improve pt-reported outcomes (PRO). In the IMerge Phase 3 (Ph3) study (NCT02598661), imetelstat, a first-in-class telomerase inhibitor, demonstrated statistically significant and meaningfully improved 8- and 24-wk transfusion independence (TI) rates, durable TI, and increased hemoglobin levels compared with placebo in heavily red blood cell (RBC) transfusion-dependent (TD) non-del(5q) LR-MDS pts who were ineligible/relapsed/refractory to ESA and naive to lenalidomide/hypomethylating agents. We also evaluated pt reported fatigue (rate of deterioration/improvement) during treatment with imetelstat or placebo. Aims: Explore impact of imetelstat or placebo on pt-reported fatigue in IMerge Ph3. Methods: To measure pt-reported fatigue, an exploratory analysis, data were collected using the validated Functional Assessment of Chronic Illness Therapy (FACIT) Scale and analyzed in all randomized pts with available fatigue data at baseline (PRO population). The FACIT is a 13-item questionnaire measuring fatigue during daily activity. Proportion of sustained meaningful deterioration/improvement was defined as percentage of pts with ≥3-point decrease/increase on the FACIT Fatigue Scale (0–52) for ≥2 consecutive treatment cycles. Time-to-deterioration/improvement was estimated by Kaplan-Meier analysis. Sensitivity analyses were performed in the intent-to-treat population and with alternate definitions of meaningful deterioration. Results: The PRO population included 118 pts on imetelstat and 57 pts on placebo. Completion rates for all PRO items were >80% at most visits throughout the study in both groups. At baseline, mean age was 71 years (range, 39–87), Eastern Cooperative Oncology Group performance status was 0 (36.0%), 1 (60.6%), or 2 (3.4%), and 62.3% of pts were male. The proportion of pts who experienced any episode of sustained, meaningful deterioration in fatigue during this study was 43.2% in the imetelstat group and 45.6% in the placebo group. Results of sensitivity analyses were similar to the main analysis. Overall, 50.0% of pts on imetelstat reported sustained meaningful improvement in fatigue vs 40.4% of pts on placebo. A shorter median time to reported first sustained meaningful improvement in fatigue occurred with imetelstat vs placebo; 28.3 vs 65.0 wks, HR=1.34 (95% CI, 0.82–2.20). After 12 wks, more pts on imetelstat reported improvement in the FACIT Fatigue Scale than on placebo, Figure a. In imetelstat-treated pts, a significantly higher proportion of responders had sustained meaningful improvement in fatigue scores vs non-responders, consistent across 8- and 24-wk TI and HI-E per IWG 2006; an association was not observed in placebo-treated pts, Figure b. Summary/Conclusion: In this heavily TD population, both imetelstat- and placebo-treated pts reported similar rates of deterioration in fatigue, suggesting imetelstat did not worsen the rate of deterioration, which has been reported with other available treatments. After 12 wks, greater improvement in fatigue was reported with imetelstat compared to placebo; pts on imetelstat were more likely to have sustained meaningful improvement in fatigue and quicker to experience it. A significant association between TI and HI-E responses and sustained meaningful improvement in fatigue support the clinical benefit of imetelstat treatment. Mikkael A. Sekeres and Valeria Santini contributed equally. Amer M. Zeidan and Uwe Platzbecker contributed equally.Keywords: Myelodysplastic syndrome, Fatigue, Therapy, Telomerase activity