Geron : Health-Related Quality of Life Outcomes In Patients with Lower-Risk Myelodysplastic Syndromes Treated with Imetelstat In the Imerge Trial

Published: 2025-06-14 14:29:06 ET GERN

Published on 06/14/2025 at 14:29

‌Background

Quality of life (QOL) in patients with lower-risk myelodysplastic syndromes (LR-MDS) often declines as anemia and associated symptoms worsen, and progressive dependence on red blood cell (RBC) transfusions affects daily life1

Thus, a significant goal of therapy is to reduce symptoms, including anemia-related fatigue, to improve QOL

0.6

0.5

0.4

0.3

0.2

0.1

0.0

Median time-to-event: Imetelstat: NE Placebo: NE

+ Censored

0 10 20 30 40 50 60 70 80 90 100 110 120 130 140

No. at risk Imetelstat Placebo

Time to first sustained improvement, weeks

113 90 73 48 36 31 25 21 13 10 6 3 2 2 1

56 48 44 27 18 12 10 8 3 3 2 2 1 0

0.6

0.5

0.4

0.3

0.2

0.1

0.0

Median time-to-event: Imetelstat: 92.1 weeks Placebo: NE

+ Censored

0 10 20 30 40 50 60 70 80 90 100 110 120 130 140

No. at risk Imetelstat Placebo

Time to first sustained improvement, weeks

113 83 64 41 32 27 23 21 14 11 7 3 2 2 1

56 42 38 21 17 13 9 6 2 2 1 1 1 0

0.6

0.5

0.4

0.3

0.2

0.1

0.0

Median time-to-event: Imetelstat: 61.0 weeks

Placebo: 44.1 weeks

+ Censored

0 10 20 30 40 50 60 70 80 90 100 110 120 130 140

No. at risk Imetelstat Placebo

Time to first sustained improvement, weeks

113 80 64 39 25 23 16 13 9 7 5 1 1 1 1

56 44 37 21 15 9 8 6 2 2 1 1 0

Imetelstat

Placebo

Nominal P=.0126

Nominal P=.1492

Nominal P=.0119

n/N=

Nominal P=.0037

Nominal P=.0157

Nominal P=.0380

n/N=

Nominal P=.0100

Nominal P=.0308

Nominal P=.0598

n/N=

Imetelstat responder Imetelstat nonresponder

34 97

32 97

24 97

Survival probability

Characteristic

Imetelstat (N=118)

Placebo (N=57)

Age, median (range), y

71.5 (44-87)

73 (39-85)

Male, n (%)

71 (60)

38 (67)

WHO classification, n (%)

RS+

73 (62)

37 (65)

RS−

44 (37)

20 (35)

IPSS risk category, n (%)

Low

80 (68)

37 (65)

Intermediate-1

38 (32)

20 (35)

Transfusion burden per IWG 2018, n (%)

HTB

97 (82)

41 (72)

LTB

21 (18)

16 (28)

Prior RBC transfusion burden, n (%)

≤6 U/8 weeks

62 (53)

31 (54)

>6 U/8 weeks

56 (48)

26 (46)

Serum EPO level, n (%)b

≤500 mU/mL

87 (74)

35 (61)

>500 mU/mL

26 (22)

20 (35)

Prior ESA, n (%)

108 (92)

50 (88)

Imetelstat, a first-in-class, direct, and competitive inhibitor of telomerase activity, was recently approved in the United States and Europe for certain adult patients with LR-MDS and transfusion-dependent (TD) anemia who have relapsed or refractory/unsatisfactory response to or are ineligible

2,3

Results

The PRO population comprised 175 patients (imetelstat, n=118; placebo, n=57)

Three placebo recipients from the intention-to-treat population were not included in the PRO population because they did not have complete baseline PRO data

Baseline characteristics were similar across treatment arms (Table 1)

for erythropoiesis-stimulating agents

- Approval was based on results of the randomized, double-blind, placebo-controlled, Phase 3 IMerge trial (NCT02598661)4

Survival probability

In IMerge, treatment with imetelstat resulted in clinically meaningful and statistically significant benefit, with a higher proportion of patients achieving ≥8-week and ≥24-week RBC transfusion independence (TI) compared with placebo

A total of 50% of imetelstat-treated patients and 40% of placebo recipients experienced a sustained, meaningful improvement in patient-reported fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale (exploratory outcome)4

This post hoc analysis reports on the effects of imetelstat treatment on patient-reported QOL measures in the Phase 3 IMerge trial

QOL, defined as an individual's perception of functioning and well-being, encompasses numerous facets, including physical, emotional, and social functioning5

Methods

IMerge is a randomized, double-blind, placebo-controlled Phase 3 trial (Figure 1)

Patient-reported outcomes (PRO) assessed in this post hoc analysis included the Quality of Life in Myelodysplasia Scale (QUALMS) questionnaire: QUALMS Total score and 2 subscale scores, physical burden (QUALMS-P) and emotional burden (QUALMS-E)6

Definition of response and timing of assessments are presented in Figure 2

Sustained meaningful improvement was defined based on previously described thresholds in

relation to improvement in hemoglobin levels ≥1.5 g/dL7

Phase 3

Double-blind, randomized

118 clinical sites in 17 countries

mg/kg active

(equ mg/kg

7.1

Imetelstat

dose

metelstat sodi

IV =118)

ivalent to 7.5

i um)

Patient population (ITT): N=178

IPSS low-risk or intermediate-1-risk MDS

R/Ra to ESAs or EPO

>500 mU/mL (ESA

ineligible)

RBC-TD: ≥4 U RBCs

every 8 weeks over 16-week prestudy

Non-del(5q)

No prior treatment with lenalidomide or HMAs

every 4 weeks (n

Stratification

Transfusion burden (4-6 U vs >6 U)

IPSS risk category (low vs intermediate-1)

R Both treatments received supportive

2:1 care, including RBC and platelet transfusions, myeloid growth factors (eg, G-CSF), and iron chelation therapy administered as needed

on-study per investigator discretion

Placebo

(n=60)

Primary endpoint

≥8-week RBC-TIb

Key secondary endpoints

≥24-week RBC-TI,c duration of RBC-TI, HI-E, safety

Other secondary endpoints

OS, PFS, time to progression to AML

Key exploratory endpoints

Changes in VAF of somatic mutations, cytogenetic response

PRO:

- Fatigue measured by FACIT-Fatigue

Safety population (treated): N=177 Imetelstat: n=118 Placebo: n=59

- Symptoms by FACT-An

Data cutoff date for PRO analysis: October 13, 2022

- QOL by QUALMS

Mean (SE) change from baseline

EPO, erythropoietin; ESA, erythropoiesis-stimulating agent; IPSS, International Prognostic Scoring System; HTB, high transfusion burden; IWG, International Working Group; LTB, low transfusion burden; RBC, red blood cell; RS, ring sideroblast; WHO, World Health Organization.

Improvements in QUALMS Total and QUALMS-P scores were observed in more patients treated with imetelstat versus placebo (Figure 3), and in patients with certain baseline characteristics (Figure 4)

118

Imetelstat

Placebo

n/N=

QUALMS Total

QUALMS-P

QUALMS-E

Patients, %

n/N, number with event/number in population; QUALMS, Quality of Life in Myelodysplasia Scale; QUALMS-E, Quality of Life in Myelodysplasia Scale - emotional burden; QUALMS-P, Quality of Life in Myelodysplasia Scale - physical burden.

n/N0=

22 8

17 6

73 37

RS+

RS status

57 26

12 41

HTB

24 13

5 2

21 16

LTB

24 7 11 7

80 37 38 20

10 35

6 3

26 20

RS−

≤6 U/8 weeks >6 U/8 weeks

Prior transfusion burden

Low Intermediate-1 ≤500 mU/mL >500 mU/mL

Transfusion burden per IWG 2018 criteria

IPSS risk group

Baseline serum EPO levels

n/N0=

29 11

73 37

RS+

15 4

44 20

RS−

40 12

97 41

HTB

19 19

4 3

21 16

LTB

10 12 5 33 10 8 4

37 38 20 87 35 26 20

RS status

≤6 U/8 weeks >6 U/8 weeks

Prior transfusion burden

Low Intermediate-1 ≤500 mU/mL >500 mU/mL

Transfusion burden per IWG 2018 criteria

IPSS risk group

Baseline serum EPO levels

43 43

39 39

41 40

N0=

31 16 15 6 23 9 23 13 38 16 8 6

73 37 44 20 57 26 61 31 97 41 21 16

RS+ RS− HTB LTB

38 13

80 37

Low

8 9 36 14 8 7

38 20 87 35 26 20

≤6 U/8 weeks >6 U/8 weeks

Prior transfusion burden

Intermediate-1 ≤500 mU/mL >500 mU/mL

RS status

Transfusion burden per IWG 2018 criteria

IPSS risk group

Baseline serum EPO levels

Imetelstat Placebo

30 97

Patients, %

Mean (SE) change from baseline

Survival probability

n/N, number with event/number in population; PRO, patient-reported outcome; QUALMS, Quality of Life in Myelodysplasia Scale; QUALMS-E, Quality of Life in Myelodysplasia Scale - emotional burden; QUALMS-P, Quality of Life in Myelodysplasia Scale - physical burden; RBC, red blood cell; TI, transfusion independence.

P values were calculated by chi-square test.

Imetelstat-treated patients maintained QOL measured by QUALMS scores (Figure 6), while placebo recipients experienced worsening QOL with a meaningful difference in least squares means in QUALMS Total and QUALMS-P scores (Table 2)

Median time to first sustained improvement in QUALMS scores (Figure 7) showed a trend of shorter time to onset with imetelstat versus placebo

−2

−4

No. at risk

Imetelstat 116

Placebo 57

102 109 101 88 81 73 64 55 51 50 50

52 54 52 49 46 40 30 28 23 21 20

7.5

5.0

2.5

0.0

−2.5

−5.0

No. at risk

Imetelstat 116

Placebo 57

102 109 101 88 80 73 64 55 51 50 50

52 54 52 49 46 40 30 28 23 21 20

7.5

2.5

−2.5

−5

No. at risk

Imetelstat 116

Placebo

102 109

52 54

101

88 81

Placebo

55 51 50 50

28 23 21 20

Imetelstat

In this post hoc analysis, numerically more imetelstat-treated patients experienced sustained improvement in QOL as measured by QUALMS Total and QUALMS-P scores compared with placebo across baseline disease characteristics

- The sustained improvement in QUALMS-P and QUALMS-E were experienced earlier in patients who received imetelstat versus placebo

A higher proportion of imetelstat responders who achieved ≥8-week, ≥24-week, or ≥1-year RBC-TI experienced sustained meaningful improvement in QUALMS Total, QUALMS-P, and QUALMS-E scores compared with nonresponders

Together, these data suggest that certain patients with LR-MDS and TD anemia who experience sustained RBC-TI with imetelstat may experience improved health-related QOL beyond fatigue

Results should be interpreted with caution given the post hoc nature of this analysis, the small sample sizes in some groups, and the limitations in the definition of meaningful change thresholds for QUALMS

Conclusions

NE, not estimable; PRO, patient-reported outcome; QUALMS, Quality of Life in Myelodysplasia Scale; QUALMS-E, Quality of Life in Myelodysplasia Scale - emotional burden; QUALMS-P, Quality of Life in Myelodysplasia Scale - physical burden.

Mean (SE) change from baseline

AML, acute myeloid leukemia; EPO, erythropoietin; ESA, erythropoiesis-stimulating agent; FACIT, Functional Assessment of Chronic Illness Therapy; FACT-An, Functional Assessment of Cancer Therapy-Anemia; G-CSF, granulocyte colony-stimulating factor; Hb, hemoglobin; HI-E, hematologic improvement-erythroid; HMA, hypomethylating agent; IPSS, International Prognostic Scoring System;

ITT, intention-to-treat; IV, intravenous; MDS, myelodysplastic syndrome; OS, overall survival; PFS, progression-free survival; PRO, patient-reported outcome; QOL, quality of life; QUALMS, Quality of Life in

Myelodysplasia Scale; R, randomized; RBC, red blood cell; R/R, relapsed or refractory; TD, transfusion dependent; TI, transfusion independence; VAF, variant allele frequency.

aReceived ≥8 weeks of ESA treatment (epoetin alfa ≥40,000 U, epoetin beta ≥30,000 U, or darbepoetin alfa 150 µg or equivalent per week) without Hb rise ≥1.5 g/dL or decreased RBC transfusion requirement ≥4 U every 8 weeks or transfusion dependence or reduction in Hb by ≥1.5 g/dL after hematologic improvement from ≥8 weeks of ESA treatment. bProportion of patients without any RBC transfusion for ≥8 consecutive weeks since entry to the trial (≥8-week RBC-TI). cProportion of patients without any RBC transfusion for ≥24 consecutive weeks since entry to the trial (≥24-week RBC-TI).

Episode of sustained, meaningful improvement:

≥9-, ≥8-, or ≥9-point increase for ≥2 consecutive assessments

in QUALMS Total score, QUALMS-P, and QUALMS-E, respectively

Timing of assessments

Baseline

Every 4 weeks during treatment

End of treatment

Every 12-16 weeks during posttreatment follow-up or start of subsequent therapy

QUALMS, Quality of Life in Myelodysplasia Scale; QUALMS-E, Quality of Life in Myelodysplasia Scale - emotional burden; QUALMS-P, Quality of Life in Myelodysplasia Scale - physical burden.

EPO, erythropoietin; IPSS, International Prognostic Scoring System; HTB, high transfusion burden; IWG, International Working Group; LTB, low transfusion burden; n/N, number with event/number in population; PRO, patient-reported outcome; QUALMS, Quality of Life in Myelodysplasia Scale; QUALMS-E, Quality of Life in Myelodysplasia Scale - emotional burden; QUALMS-P, Quality of Life in Myelodysplasia Scale - physical burden; RS, ring sideroblast.

Improvement in sustained meaningful QUALMS was seen in more patients who responded to imetelstat versus those who did not respond across measures of response (Figure 5)

The proportion of patients with improvements in QUALMS-P was significantly higher among those

who achieved ≥8-week, ≥24-week, or ≥1-year RBC-TI with imetelstat versus nonresponders

A similar trend was observed for QUALMS Total and QUALMS-E scores

Patients, %

ITT, intention-to-treat; PRO, patient-reported outcome; QUALMS, Quality of Life in Myelodysplasia Scale; QUALMS-E, Quality of Life in Myelodysplasia Scale - emotional burden; QUALMS-P, Quality of Life in Myelodysplasia Scale - physical burden.

Score

Imetelstat

LS mean (95% CI) change from baseline (n=118)

Placebo

LS mean (95% CI) change from baseline (n=60)

LS mean (95% CI) difference

Nominal

P value

QUALMS Total

−0.55 (−2.85, 1.76)

−5.21 (−8.35, −2.07)

4.66 (0.86, 8.46)

.016

QUALMS - physical burden

−0.41 (−3.18, 2.36)

−6.75 (−10.53, −2.98)

6.34 (1.77, 10.91)

.007

QUALMS - emotional burden

−0.16 (−3.12, 2.80)

−4.52 (−8.56, −0.48)

4.36 (−0.53, 9.25)

.080

ITT, intention-to-treat; IPSS, International Prognostic Scoring System; LS, least squares; QOL, quality of life; QUALMS, Quality of Life in Myelodysplasia Scale; RMMM, repeated measurement mixed model. aAn RMMM was conducted to summarize the change in QUALMS scores from baseline over time, using all available longitudinal data and adjusting for stratification factors. The RMMM included the change in scores as the explained variable and baseline score, time, treatment, time and treatment interaction, and study stratification factors (prior RBC transfusion burden and IPSS risk group) as covariates (fixed effects) as explanatory variables. The model included a random effect for individuals to account for the within-individual correlation in the longitudinal assessments and is based on all data up to cycle 30 (ie, up to the cycle at which data for both treatment arms is available). The overall effects of imetelstat on QUALMS scores were evaluated from the model comparing the LS means of change in scores estimated in the 2 treatment groups using all available data up to cycle 30.

Patients, %

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RYTELO® (imetelstat) for injection, for intravenous use. Package insert. Geron Corporation; 2024.

RYTELO® (imetelstat) summary of product characteristics. Geron Corporation; 2025.

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The authors thank all the patients and caregivers for their participation in this study and acknowledge the collaboration and commitment of all investigators and their research support staff

This study was funded by Geron Corporation. All authors contributed to and approved the presentation; writing and editorial support were provided by Meredith Rogers, MS, CMPP, of The Lockwood Group (Stamford, CT, USA), funded by Geron Corporation

Copies of this poster obtained through the Quick Response (QR) code are for personal use only and may not be reproduced without permission from the author of this poster.

HEALTH-RELATED QUALITY OF LIFE OUTCOMES IN PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES TREATED WITH IMETELSTAT IN THE IMERGE TRIAL

María Díez-Campelo,1 Esther Natalie Oliva,2 Valeria Santini,3 Amer M. Zeidan,4 Uwe Platzbecker,5 Rami S. Komrokji,6 Pierre Fs enaux,7 Michael R. Savona,8 Yazan F. Madanat,9 David Valcárcel,10 Kristin Creel,11 Manal M'hari,11 Libo Sun,12 Ying Wan,12 Tymara Berry,12 Faye Feller,12 Shyamala Navada,12 Mikkael A. Sekeres13

1University Hospital of Salamanca, Salamanca, Spain; 2Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio Calabria, Italy; 3MDS Unit, Hematology, DMSC University of Florence, AOUC, Florence, Italy; 4Yale School of Medicine and Yale Cancer Center, Yale University, New Haven, CT, USA; 5National Center for Tumor Diseases (NCT), University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany; 6Moffitt Cancer Center, Tampa, FL, USA; 7Hôpital Saint-Louis, Université de Paris 7, Paris, France; 8Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA; 9Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA; 10Hospital Universitario Vall d'Hebron, Barcelona, Spain; 11Modus Outcomes, a company of THREAD, Lyon, France; 12Geron Corporation, Foster City, CA, USA; 13Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA

PS1639

Presented at the 30th European Hematology Association Annual Congress; June 12-15, 2025; Milan, Italy

ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT02598661

Contact information: [email protected]

Disclaimer

Geron Corporation published this content on June 14, 2025, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on June 14, 2025 at 18:28 UTC.