Kooperativer Bibliotheksverbund

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4248-4248

Abstract: Background: Current treatment options for red blood cell (RBC) transfusion-dependent (TD) patients with lower risk (LR) myelodysplastic syndromes (MDS) relapsed after or refractory to erythropoiesis-stimulating agents (ESAs) have limited efficacy and durability; new approaches are needed. Imetelstat is a 13-mer lipid-conjugated oligonucleotide that targets the RNA template of human telomerase and is a competitive inhibitor of telomerase enzymatic activity (Asai et al, Cancer Res 2003; Herbert et al, Oncogene 2005). Preclinical, in vivo xenograft models (Dikmen et al, Cancer Res 2005; Hochreiter et al, Clin Cancer Res 2006) and preliminary clinical data from a pilot study conducted at Mayo Clinic (Tefferi et al, Blood Cancer Journal 2016) supported initiation of a study in TD LR MDS patients. A Phase 2 study of imetelstat, IMerge, demonstrated an 8-week RBC transfusion independence (RBC-TI) rate of 42%, 24-week RBC-TI rate of 29%, and 68% erythroid hematologic improvement (HI-E) rate in 38 heavily TD patients (median prior RBC transfusion burden 8 units / 8 weeks over the 16 weeks pre-study period) with LR MDS. Responses were durable with median duration of 8-week RBC-TI of 85.9 weeks by Kaplan Meier estimates (range 8.0-140.9) (Steensma ASH 2018, Fenaux EHA 2019). These Phase 2 results provided further evidence of potential clinical benefit of imetelstat treatment in TD LR MDS, and supported initiation of a Phase 3 trial. Methods: IMerge is two-part, Phase 2/3 study (ClinicalTrials.gov: NCT02598661). The Phase 2 portion of the study described above is closed for enrollment. The Phase 3 portion of the study is open for enrollment of adult patients with International Prognostic Scoring System (IPSS) low or intermediate-1 risk, non-del(5q) MDS, who are TD, are relapsed after or refractory to ESAs, and have not received treatment with lenalidomide or hypomethylating agents. The study is a randomized (2:1) double-blind, placebo-controlled trial to compare efficacy of imetelstat vs. placebo that will enroll approximately 170 patients and will be conducted at approximately 90 centers in North America, Europe, Asia and Middle East. Imetelstat will be administered as 2-hour IV infusion every 4 weeks at 7.5 mg/kg. The primary endpoint of the study is to assess the rate of RBC-TI lasting ≥8 weeks. Secondary endpoints include safety, rate of RBC-TI ≥24 weeks, time to RBC-TI start, RBC-TI duration, rate of HI-E, the amount and relative change in RBC transfusions, rate of CR or PR, overall survival, progression of MDS, pharmacokinetics and effect of treatment on quality of life. Biomarkers relevant to the mechanism of action of imetelstat will be assessed to demonstrate target inhibition and their association with clinical responses. Cytogenetics and mutation analyses will be performed to evaluate the impact of imetelstat on reduction/depletion of malignant clones leading to disease modification. Disclosures Platzbecker: Novartis: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria. Steensma:Astex: Consultancy; Arrowhead: Equity Ownership; Summer Road: Consultancy; Onconova: Consultancy; Aprea: Research Funding; Pfizer: Consultancy; Stemline: Consultancy; H3 Biosciences: Other: Research funding to institution, not investigator.. Santini:Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria; Acceleron: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Menarini: Membership on an entity's Board of Directors or advisory committees. Germing:Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria; Amgen: Honoraria. Font:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees. Díez-Campelo:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Patnaik:Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees. Sherman:Geron Corporation: Employment, Equity Ownership. Dougherty:Geron Corporation: Employment, Equity Ownership. Feller:Geron Corporation: Employment. Sun:Geron Corporation: Employment, Equity Ownership. Wan:Geron Corporation: Employment, Equity Ownership. Huang:Geron Corporation: Employment, Equity Ownership. Rizo:Geron Corporation: Employment, Equity Ownership. Fenaux:Celgene Corporation: Honoraria, Research Funding; Aprea: Research Funding; Astex: Honoraria, Research Funding; Jazz: Honoraria, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-127435

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 5214-5214

Abstract: In a randomized study of single-agent eltrombopag (EPAG; n=64) versus placebo (PBO; n=34) in thrombocytopenic patients with advanced myelodysplastic syndromes or acute myeloid leukemia (AML), median overall survival (OS) was 27 weeks for EPAG versus 15.7 weeks for PBO (hazard ratio [HR]: 0.73). In addition to standard supportive care, disease-modifying treatments were generally permitted at any time at the investigator's discretion. To explore the role of concomitant anticancer therapy in this study population, a post hoc subgroup analysis was conducted in patients in each treatment group who received anticancer treatment. Methods Anticancer treatment was grouped post hoc into the following categories: palliative treatment (eg, hydroxyurea, low-dose cytarabine), hypomethylating agents (HMAs; eg, azacitidine and decitabine), induction chemotherapy (eg, 7 + 3; mitoxantrone, etoposide, and cytarabine, etc), and other (eg, lenalidomide). Baseline characteristics and safety/efficacy parameters were examined in this subgroup of patients. Results While on study treatment, a similar proportion of patients in both treatment arms of the trial received anticancer therapy (EPAG, n=28 [44%]; PBO, n=13 [38%] ). The majority of patients receiving anticancer therapy in both the EPAG (64%) and PBO (54%) arms received palliative treatments (primarily hydroxyurea and low-dose cytarabine) followed by HMAs (Table). Induction chemotherapy was received by 11% of patients in the EPAG subgroup, compared with no patients in the PBO subgroup. For the subgroup of patients who received anticancer therapy, EPAG patients had higher baseline median platelet counts and absolute neutrophil counts, and a lower incidence of poor prognosis karyotype (Table). The percentage of patients with AML and those who were platelet transfusion dependent were similar between treatment arms at baseline (Table). All patients in both treatment groups experienced ≥1 adverse event (AE) while on study treatment. A lower proportion of EPAG patients experienced a serious AE (SAE) on therapy compared with PBO patients, and proportionately fewer infection-related SAEs were reported in EPAG versus PBO patients (Table). Pyrexia SAEs were higher in the EPAG (5 [18%]) arm versus the PBO (1 [8%] ) arm. In the subgroup of patients receiving anticancer therapy, a similar proportion of EPAG and PBO patients experienced Grade ≥3 hepatobiliary events (3 [11%] vs 1 [8%] ). Three (11%) EPAG patients experienced Grade ≥3 renal and 2 (7%) thromboembolic events on study drug, whereas no PBO patients experienced these events. A lower proportion of patients on EPAG (18%) experienced AEs that led to discontinuation of study treatment compared with those on PBO (46%). A lower proportion of EPAG patients (32%) died on therapy compared with PBO (69%); the primary cause of death in both arms was the underlying disease. Median platelet counts for EPAG patients receiving anticancer treatment increased above baseline, whereas median platelet counts remained stable at baseline levels for PBO patients. A higher proportion of EPAG patients than PBO patients achieved platelet (50% vs 31%) and red blood cell (RBC; 29% vs 8%) transfusion independence for ≥8 weeks (Table). Bleeding events (Grade ≥3) were reported in fewer EPAG patients (11%) versus PBO patients (38%). When censoring patients at the start of anticancer treatment, no apparent difference in OS was observed between treatment arms (HR: 0.97). Summary/conclusion In the subgroup who received anticancer therapy, EPAG patients had higher incidences of platelet and RBC transfusion independence, higher median platelet counts, and lower incidences of bleeding and infectious complications compared with PBO patients, with selected SAEs occurring at higher rates. These results support the safety profile of EPAG in combination with a variety of anticancer agents. In addition, these data suggest a possible beneficial supportive care effect in patients receiving concomitant therapy with EPAG and anticancer treatment. Further studies of EPAG in combination with anticancer therapy are warranted to confirm these hypotheses. Disclosures: Platzbecker: GlaxoSmithKline: Honoraria. Off Label Use: Eltrombopag is a TPO receptor agonist that is used for the treatment of thrombocytopenia due to various diseases. It is approved in cITP and now being evaluated for the correction of thrombocytopenia in subjects with MDS/AML. Wong:GlaxoSmithKline: Consultancy, Honoraria, Research Funding, Speakers Bureau. Verma:GlaxoSmithKline: Research Funding. Abboud:Alexion: Honoraria; Ariad: Honoraria; Novartis: Honoraria; Teva: Speakers Bureau. Greenberg:Amgen: Research Funding; GlaxoSmithKline: Research Funding; KaloBios: Research Funding; Novartis: Research Funding; Onconova: Research Funding. Lyons:Novartis: Research Funding; GlaxoSmithKline: Research Funding; Amgen: Honoraria, Research Funding. Santini:Novartis: Honoraria; Janssen: Honoraria; GlaxoSmithKline: Honoraria; Celgene: Honoraria. Cheng:GlaxoSmithKline: Speakers Bureau. Dougherty: GlaxoSmithKline: Employment. Mannino:GlaxoSmithKline: Employment. Mostafa Kamel:GlaxoSmithKline: Employment, Equity Ownership. Chan:GlaxoSmithKline: Employment. Stone:GlaxoSmithKline: Employment. Giagounidis:GlaxoSmithKline: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V122.21.5214.5214

Language: English

Publisher: American Society of Hematology

Publication Date: 2013

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In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 1 ( 2021-01-01), p. 48-56

Abstract: Patients with lower-risk (LR) myelodysplastic syndromes (MDS) who are RBC transfusion dependent and have experienced relapse after or are refractory to erythropoiesis-stimulating agent (ESA) have limited treatment options. High telomerase activity and human telomerase reverse-transcription expression in clonal hematopoietic cells have been reported in patients with MDS. Imetelstat, a first-in-class competitive inhibitor of telomerase enzymatic activity, targets cells with active telomerase. We report efficacy, safety, and biomarker data for patients with LR MDS who are RBC transfusion dependent and who were relapsed/refractory to ESAs. PATIENTS AND METHODS In this two-part phase II/III study (MDS3001), the primary end point was 8-week RBC transfusion independence (TI) rate, with key secondary end points of 24-week RBC TI rate, TI duration, and hematologic improvement-erythroid. RESULTS Data from the phase II part of the study are reported. Of 57 patients enrolled and treated (overall population), 38 were non-del(5q) and hypomethylating agent and lenalidomide naïve (subset population). The 8- and 24-week RBC TI rates in the overall population were 37% and 23%, respectively, with a median TI duration of 65 weeks. In the subset population, 8- and 24-week RBC TI rates were 42% and 29%, respectively, with a median TI duration of 86 weeks. Eight-week TI rate was observed across all subgroups evaluated. Cytogenetic and mutational data revealed a reduction of the malignant clones, suggesting disease modification activity. The most common adverse events were cytopenias, typically reversible within 4 weeks. CONCLUSION Imetelstat treatment results in a meaningful, durable TI rate across a broad range of heavily transfused patients with LR MDS who are ineligible for or relapsed/refractory to ESAs. Biomarker analyses indicated effects on the mutant malignant clone.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.20.01895

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2021

detail.hit.zdb_id: 2005181-5

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. TPS7079-TPS7079

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2016.34.15_suppl.TPS7079

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2016

detail.hit.zdb_id: 2005181-5

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 45-46

Abstract: Background: Myelofibrosis (MF) is a life-threatening myeloproliferative neoplasm characterized by splenomegaly and debilitating symptoms, such as fatigue, pruritus, night sweats, fever, bone pain, and weight loss that impact quality of life (QoL). Imetelstat, a first-in-class telomerase inhibitor, demonstrated clinical benefits in terms of symptom response and potential improvement in overall survival in a pilot study in MF patients (pts) (Tefferi et al, NEJM 2015) and in IMbark, a Phase 2 study in MF pts relapsed or refractory (R/R) to a Janus associated kinase (JAK) inhibitor (Mascarenhas et al, ASH 2018 #685). Aims: We assessed the effects of imetelstat on MF symptom burden and QoL in IMbark, and the correlations of MF-related symptoms measured by modified Myelofibrosis Symptom Assessment Form (MFSAF) 2.0 and other patient-reported outcome (PRO) endpoints. Methods: IMbark (MYF2001; NCT02426086) is a two-dose, randomized, single-blinded, Phase 2 study of imetelstat in R/R intermediate-2/high-risk MF pts, who received imetelstat 9.4 mg/kg or 4.7 mg/kg IV every 3 weeks. Symptom response, one of the co-primary endpoints, was defined as ≥50% reduction in total symptom score (TSS) from baseline to Week 24 as measured by the modified MFSAF 2.0 e-diary. The TSS was calculated as the 7-day average of daily TSS, which is the summation of 6 individual symptom scores (night sweats, itchiness, abdominal discomfort, pain under ribs on left side, early satiety, bone or muscle pain). Correlation of TSS with other PROs was explored: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), Brief Pain Inventory (BP-I), and Patient Global Impression of Change (PGIC). Results: All 107 pts enrolled in IMbark were symptomatic, with baseline mean TSS scores of 25.7 in the 9.4 mg/kg arm (N=59) and 24.6 in the 4.7 mg/kg arm (N=48), indicating a high symptom burden. Pts in both arms had ≥96.5% mean compliance rates with completion of the e-diary. Treatment with imetelstat demonstrated a statistically significant dose-related improvement in TSS symptom response rate at Week 24 for 9.4 mg/kg vs 4.7 mg/kg (32.1% vs 6.3%, p=0.001) and at any time (52.5% vs 27.1%, p=0.010). A higher proportion of pts in the 9.4 mg/kg arm than in the 4.7 mg/kg arm achieved ≥50% reduction in 5 individual symptoms, including night sweats, itchiness, abdominal pressure, pain under left ribs, and early satiety. Based on EORTC QLQ-C30, improvements at Week 24 relative to baseline were seen in the imetelstat 9.4 mg/kg arm for global health status, all 5 function subscales, and all 3 symptoms. Notably for fatigue (a common MF symptom which was not measured in MFSAF v2.0), pts in the 9.4 mg/kg arm had improvement at Week 24 relative to baseline, compared to the pts in the 4.7 mg/kg arm (LS means -13.3 vs -3.1, p=0.042). The TSS symptom responses were shown to correlate with other PROs. Compared to pts in the 4.7 mg/kg arm, TSS symptom responders in the 9.4 mg/kg arm achieved significantly greater improvements in the global health status (p=0.004), fatigue (p=0.009), pain (p=0.033), and most of the functional scales in EORTC QLQ-C30. Pain scores per the modified MFSAF v2.0 correlated with the pain scores in EORTC QLQ-C30 and BP-I (correlation coefficients 0.5-0.6). More than 90% of TSS symptom responders in the 9.4 mg/kg arm also characterized their condition as having had either "very much improvement" (36.4%) or "somewhat improvement" (54.6%) in PGIC. Conclusion: These data show a dose-related, clinically meaningful improvement in overall and individual MF symptoms as measured by MFSAF 2.0 with imetelstat treatment in pts who are JAK inhibitor R/R. TSS symptom responders treated with imetelstat 9.4 mg/kg also had improvement in QoL as measured by EORTC QLQ-C30. The data further support the robustness of overall and individual symptom improvement in pts with MF as evidenced by the correlation of modified MFSAF v2.0 with other PROs such as EORTC QLQ-C30, PGIC, and BP-I. Disclosures Mascarenhas: Incyte, Kartos, Roche, Promedior, Merck, Merus, Arog, CTI Biopharma, Janssen, and PharmaEssentia: Other: Research funding (institution); Celgene, Prelude, Galecto, Promedior, Geron, Constellation, and Incyte: Consultancy. Komrokji:Geron: Honoraria; BMS: Honoraria, Speakers Bureau; Acceleron: Honoraria; Novartis: Honoraria; Incyte: Honoraria; JAZZ: Honoraria, Speakers Bureau; AbbVie: Honoraria; Agios: Honoraria, Speakers Bureau. Cavo:Jannsen, BMS, Celgene, Sanofi, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, Adaptive: Consultancy, Honoraria. Niederwieser:Novartis: Speakers Bureau; Amgen: Speakers Bureau; Cellectis: Membership on an entity's Board of Directors or advisory committees; Daiichi: Research Funding. Reiter:Gilead: Other: travel support ; Incyte: Consultancy, Other: travel support ; AOP: Consultancy, Other: travel support ; Celgene,: Consultancy, Other: travel support ; Abbvie: Consultancy, Other: travel support ; Deciphera: Consultancy, Other: travel support ; Blueprint: Consultancy, Other: travel support ; Novartis: Consultancy, Honoraria, Other: travel support , Research Funding. Scott:Agios, BMS: Honoraria; BMS, Novartis: Research Funding; Alexion, Incyte, Novartis, Regeneron: Consultancy. Baer:AbbVie: Other: Institutional research funding; Astellas: Other: Institutional research funding; Forma: Other: Institutional research funding; Incyte: Other: Institutional research funding; Kite: Other: Institutional research funding; Oscotec: Other: Institutional research funding; Takeda: Other: Institutional research funding. Hoffman:Dompe: Research Funding; Protagonist: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Forbius: Consultancy. Odenike:AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astex Pharmaceuticals, NS Pharma, Gilead Sciences, Janssen Oncology, Oncotherapy, Agios, CTI/Baxalta, Aprea: Other: Institutional research funding; Astra Zeneca: Research Funding; Incyte: Other: Institutional research funding; Impact Biomedicines: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sherman:Geron Corp: Current Employment, Current equity holder in publicly-traded company. Dougherty:Geron Corp: Current Employment, Current equity holder in publicly-traded company. Feller:Geron Corp: Current Employment, Current equity holder in private company. Huang:Geron Corp: Current Employment, Current equity holder in publicly-traded company. Rizo:Geron Corp: Current Employment, Current equity holder in publicly-traded company. Sun:Geron Corp: Current Employment, Current equity holder in publicly-traded company. Wan:Geron Corp: Current Employment, Current equity holder in publicly-traded company. Vannucchi:AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Blueprint: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-138823

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 6826-6829

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-160364

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 685-685

Abstract: Background: Imetelstat, a 13-mer oligonucleotide that specifically targets the RNA template of human telomerase, is a potent competitive inhibitor of telomerase enzymatic activity (Asai Cancer Res 2003; Herbert Oncogene 2005). Clinical activity and an acceptable safety profile were reported in a 33-patient pilot study in intermediate-2 (int-2) or high-risk myelofibrosis (MF), where 48% of patients had been previously treated with a Janus Kinase inhibitor (JAKi) (Tefferi N Engl J Med 2015). Here, we report the results of a phase 2 clinical study of imetelstat at two dose levels in patients with MF (MYF2001, NCT02426086). Methods: A randomized, multicenter, phase 2 study of two doses of imetelstat (9.4 mg/kg or 4.7 mg/kg IV, every 3 weeks) was performed in adults with DIPSS int-2 or high-risk MF that was relapsed/refractory to prior JAKi therapy (ie, either no reduction in splenomegaly after 12 weeks or worsening splenomegaly at any time after the start of JAKi therapy). Diagnosis of primary, post-essential thrombocythemia, or post-polycythemia vera MF was required; other eligibility criteria included measurable splenomegaly (by magnetic resonance imaging [MRI]), active MF-related systemic symptoms and platelet count ≥75 x 109/L. Primary endpoints were spleen response rate (% achieving ≥ 35% spleen volume reduction [SVR] by MRI) and symptom response rate (% achieving ≥ 50% reduction in total symptom score [TSS] per Myelofibrosis Symptom Assessment Form (MFSAF) v2 at week 24. Key secondary endpoints included safety, overall survival (OS), treatment response, molecular response, and pharmacokinetic and pharmacodynamic relationships. Results: 107 patients were enrolled at 55 institutions (48 on 4.7 mg/kg; 59 on 9.4 mg/kg). Baseline characteristics are shown in the Table. Additionally, median time on JAKi was 23 (0.9-89.7) mo, and median platelet count was 147 x 109/L. Triple-negative (TN; ie, no mutations of JAK2, MPL, or CALR) comprised 24.8% of patients and 67.6% were considered high molecular risk (HMR; ie, ≥ 1 mutation of ASXL1, EZH2, SRSF2, or IDH1/2). At the time of clinical cutoff, patients were followed for a median 22.6 (0.2-27.4) mo, including a median treatment duration of 6.2 (0.0-27.2) mo. Median duration on treatment was longer on the 9.4 mg/kg arm (7.7 mo) than on the 4.7 mg/kg arm. Six (10.2%) patients in the 9.4 mg/kg arm had a spleen response per MRI, with no responses on the 4.7 mg/kg arm (Figure 1). Nineteen (32%) patients in the 9.4 mg/kg arm and 3 (6%) patients in the 4.7 mg/kg arm had a symptom response (TSS reduction ≥ 50%) (Figure 2). Median OS in the 9.4 mg/kg arm has not been reached, while median OS was 19.9 mo in the 4.7 mg/kg arm. The 18-mo survival rates were 76.7% and 62.9% for the 9.4 mg/kg and 4.7 mg/kg arms, respectively. Sensitivity analyses censoring patients at time of dose escalation for subsequent JAKi therapy or allogeneic stem cell transplant generated similar results. In the 9.4 mg/kg arm, an association was observed between patients who were TN and OS (median OS has not been reached for TN patients and was 23.6 mo for non-TN patients). Spleen response rate was higher in patients with 1 HMR mutation (ASXL1, EZH2, SRSF2, or IDH1/2. The most common adverse events on treatment (all grades) at 9.4 mg/kg were thrombocytopenia (49%), anemia (44%), neutropenia (36%), and nausea (34%) and at 4.7 mg/kg were diarrhea (38%), nausea (31%), anemia (31%), and thrombocytopenia (23%). Grade 3/4 neutropenia and thrombocytopenia were more frequent with 9.4 mg/kg (34% and 42%, respectively) than 4.7 mg/kg (13% and 29%, respectively); most cytopenias resolved within 4 weeks. Grade 3/4 LFT elevations were observed in 7 patients on study. Imetelstat-related hepatic toxicities, confirmed by an independent Hepatic Review Committee, were not observed. Conclusions: Imetelstat at 9.4 mg/kg IV every 3 weeks has demonstrated clinical activity in int-2 or high-risk MF patients who are relapsed/refractory to JAKi, notably in observed OS. Though no formal study has reported survival for patients who are truly relapsed/refractory to JAKi, median OS of patients who were previously treated with JAKi has been reported to be 12-14 mo (Kuykendall Ann Hematol 2018; Newberry Blood 2017). The safety profile for imetelstat was considered acceptable for this poor-prognosis population. Imetelstat at 9.4 mg/kg IV every 3 weeks is a promising agent for JAKi-pretreated MF patients and warrants further testing in clinical trials. Disclosures Mascarenhas: Roche: Research Funding; Merck: Research Funding; Novartis: Research Funding; Promedior: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Komrokji:Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Cavo:Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Niederwieser:Novartis: Research Funding; Miltenyi: Speakers Bureau. Reiter:Incyte: Consultancy, Honoraria. Scott:Celgene: Consultancy, Research Funding; Agios: Consultancy; Alexion: Consultancy; Novartis: Research Funding. Hoffman:Janssen: Research Funding; Merus: Research Funding; Incyte: Research Funding; Summer Road: Research Funding; Formation Biologics: Research Funding. Odenike:ABBVIE: Honoraria, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; CTI/Baxalta: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Dava Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oncotherapy Science: Research Funding; Agios: Research Funding; Celgene: Research Funding; NS Pharma: Research Funding; Janssen: Research Funding; Astex: Research Funding; Gilead Sciences: Research Funding. Bussolari:Janssen: Employment, Equity Ownership. Zhu:Janssen: Employment, Equity Ownership. Huang:Janssen: Employment, Equity Ownership. Rose:Janssen: Employment, Equity Ownership. Sherman:Janssen: Employment, Equity Ownership. Dougherty:Janssen: Employment, Equity Ownership. Feller:Janssen: Employment, Equity Ownership. Kiladjian:AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-115163

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 23 ( 2023-09), p. S186-

Type of Medium: Online Resource

ISSN: 2152-2650

URL: Article

DOI: 10.1016/S2152-2650(23)00612-2

Language: English

Publisher: Elsevier BV

Publication Date: 2023

detail.hit.zdb_id: 2540998-0

detail.hit.zdb_id: 2193618-3

In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 23 ( 2023-09), p. S186-

Type of Medium: Online Resource

ISSN: 2152-2650

URL: Article

DOI: 10.1016/S2152-2650(23)00613-4

Language: English

Publisher: Elsevier BV

Publication Date: 2023

detail.hit.zdb_id: 2540998-0

detail.hit.zdb_id: 2193618-3

In: HemaSphere, Ovid Technologies (Wolters Kluwer Health), Vol. 7, No. S3 ( 2023-08), p. e99899f4-

Type of Medium: Online Resource

ISSN: 2572-9241

URL: Article

DOI: 10.1097/01.HS9.0000975644.99899.f4

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 2023

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