{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T08:24:27Z","timestamp":1791102267635,"version":"4.1.0"},"reference-count":26,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"35","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2025,12,10]]},"abstract":"<jats:p>\n                    On June 6, 2024, the US Food and Drug Administration (FDA) approved imetelstat (RYTELO, Geron) for adults with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia requiring \u22654 red blood cell units over 8 weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents. The approval was based on a randomized (2:1), double-blind, placebo-controlled multicenter trial, Study MDS3001. In the protocol-specified primary analysis, the \u22658-week RBC transfusion independence (RBC-TI) rate was 39.8% (95% CI, 30.9 to 49.3) in the imetelstat group versus 15% (95% CI, 7.1 to 26.6) in the placebo group (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; .001). This was supported by the rate of \u226524-week RBC-TI of 28% (95% CI, 20.1 to 37) in the imetelstat group versus 3.3% (95% CI, 0.4 to 11.5) in the placebo group (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; .001). However, there was no major difference between arms regarding the key secondary end point of erythroid response (HI-E) per International Working Group 2006 criteria or secondary end points reflective of a disease-modifying effect such as complete remission rate and overall survival. The most common adverse reactions were thrombocytopenia, leukopenia, neutropenia, increased liver enzymes, fatigue, prolonged partial thromboplastin time, arthralgia\/myalgia, COVID-19, and headache. The rate of grade 3 to 4 neutropenia and thrombocytopenia were 72% and 65%, respectively, in the imetelstat arm compared with 7% and 8% in the placebo arm. Despite the high incidence of neutropenia and thrombocytopenia, the FDA determined that the benefits outweighed the risks in this patient population with high unmet need. Postmarketing requirements were issued to evaluate long-term safety and to conduct a randomized trial comparing at least two dosages of imetelstat to potentially minimize risks of imetelstat treatment and improve tolerability.\n                  <\/jats:p>","DOI":"10.1200\/jco-25-01369","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T19:59:46Z","timestamp":1761335986000},"page":"3760-3768","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":5,"title":["US Food and Drug Administration Approval Summary: Imetelstat for Selected Patients With Low- to Intermediate-1 Risk Myelodysplastic Syndromes With Transfusion-Dependent Anemia"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct02598661","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1809-0417","authenticated-orcid":true,"given":"Nina","family":"Kim","sequence":"first","affiliation":[{"name":"Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Dianne","family":"Pulte","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5981-1332","authenticated-orcid":true,"given":"Lori A.","family":"Ehrlich","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5892-8141","authenticated-orcid":true,"given":"Alexei C.","family":"Ionan","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5959-2301","authenticated-orcid":true,"given":"Spencer","family":"Haupert","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9700-4037","authenticated-orcid":true,"given":"Jonathon","family":"Vallejo","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Green","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier G.","family":"Blanco","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0762-5844","authenticated-orcid":true,"given":"Sarah E.","family":"Dorff","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Booth","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4488-1616","authenticated-orcid":true,"given":"Moran","family":"Choe","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Gehrke","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4650-0513","authenticated-orcid":true,"given":"Vishal","family":"Bhatnagar","sequence":"additional","affiliation":[{"name":"Oncology Center of Excellence, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4973-5297","authenticated-orcid":true,"given":"Marc","family":"Theoret","sequence":"additional","affiliation":[{"name":"Oncology Center of Excellence, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4771-9923","authenticated-orcid":true,"given":"Richard","family":"Pazdur","sequence":"additional","affiliation":[{"name":"Oncology Center of Excellence, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8362-1977","authenticated-orcid":true,"given":"R. Angelo","family":"De Claro","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8462-9994","authenticated-orcid":true,"given":"Kelly J.","family":"Norsworthy","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.6.2079"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-03-420489"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-021-01265-7"},{"key":"e_1_3_8_5_2","first-page":"1588","article-title":"Predicting survival and leukemic evolution in patients with myelodysplastic syndrome","volume":"91","author":"Malcovati L","year":"2006","unstructured":"Malcovati L, Della Porta MG, Cazzola M: Predicting survival and leukemic evolution in patients with myelodysplastic syndrome. Haematologica 91:1588-1590, 2006","journal-title":"Haematologica"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26984"},{"key":"e_1_3_8_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2023.101114"},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2024.2422844"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2022.05.001"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.266817"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.212217"},{"key":"e_1_3_8_12_2","unstructured":"National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in oncology (NCCN Guidelines) for myeloysplastic syndromes V.2.2025. 2025. https:\/\/www.nccn.org"},{"key":"e_1_3_8_13_2","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.8.10.8130"},{"key":"e_1_3_8_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2013.07.022"},{"key":"e_1_3_8_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2013.06.011"},{"key":"e_1_3_8_16_2","volume-title":"Guidance for Industry Expedited Programs for Serious Conditions\u2014Drugs and Biologics","author":"U.S. Food and Drug Administration","year":"2014","unstructured":"U.S. Food and Drug Administration: Guidance for Industry Expedited Programs for Serious Conditions\u2014Drugs and Biologics. 2014. https:\/\/www.fda.gov\/media\/86377\/download"},{"key":"e_1_3_8_17_2","volume-title":"Drugs@FDA [database on the internet]","author":"U.S. Food and Drug Administration","unstructured":"U.S. Food and Drug Administration: Drugs@FDA [database on the internet]. Imetelstat. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2024\/217779Orig1s000MultidisciplineR.pdf"},{"key":"e_1_3_8_18_2","volume-title":"A Study to Evaluate Imetelstat (GRN163L) in Transfusion-dependent Patients with IPSS Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) that is Relapsed\/Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment","author":"Geron Corp","year":"2022","unstructured":"Geron Corp: A Study to Evaluate Imetelstat (GRN163L) in Transfusion-dependent Patients with IPSS Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) that is Relapsed\/Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment. 2022. https:\/\/cdn.clinicaltrials.gov\/large-docs\/61\/NCT02598661\/Prot_000.pdf"},{"key":"e_1_3_8_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01724-5"},{"key":"e_1_3_8_20_2","volume-title":"Functional Assessment of Cancer Therapy\u2014Anemia (FACT-An) Version 4","year":"1997","unstructured":"Functional Assessment of Cancer Therapy\u2014Anemia (FACT-An) Version 4. FACIT.org; c1987, 1997. https:\/\/www.facit.org\/measures\/fact-an"},{"key":"e_1_3_8_21_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.140335"},{"key":"e_1_3_8_22_2","volume-title":"Functional Assessment of Chronic Illness Therapy\u2014Fatigue Scale (FACIT-Fatigue) Version 4","year":"1997","unstructured":"Functional Assessment of Chronic Illness Therapy\u2014Fatigue Scale (FACIT-Fatigue) Version 4. FACIT.org; c1987, 1997. https:\/\/www.facit.org\/measures\/facit-fatigue"},{"key":"e_1_3_8_23_2","volume-title":"Drugs@FDA [database on the internet]","author":"U.S. Food and Drug Administration","unstructured":"U.S. Food and Drug Administration: Drugs@FDA [database on the internet]. Imetelstat USPI. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/217779s000lbl.pdf"},{"key":"e_1_3_8_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2024014865"},{"key":"e_1_3_8_25_2","volume-title":"Drugs@FDA [database on the internet]","author":"U.S. Food and Drug Administration","unstructured":"U.S. Food and Drug Administration: Drugs@FDA [database on the internet]. Decitabine. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2006\/021790s000_Dacogen_MedR.pdf"},{"key":"e_1_3_8_26_2","volume-title":"Drugs@FDA [database on the internet]","author":"U.S. Food and Drug Administration","unstructured":"U.S. Food and Drug Administration: Drugs@FDA [database on the internet]. Azacitidine. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2004\/50-794_Vidaza_Medr_P1.pdf"},{"key":"e_1_3_8_27_2","volume-title":"March 14, 2024: Meeting of the Oncologic Drugs Advisory Committee Meeting Announcement","author":"U.S. Food and Drug Administration","unstructured":"U.S. Food and Drug Administration: March 14, 2024: Meeting of the Oncologic Drugs Advisory Committee Meeting Announcement. https:\/\/www.fda.gov\/advisory-committees\/advisory-committee-calendar\/march-14-2024-meeting-oncologic-drugs-advisory-committee-meeting-announcement-03142024"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO-25-01369","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T23:00:31Z","timestamp":1764975631000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO-25-01369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,10]]},"references-count":26,"journal-issue":{"issue":"35","published-print":{"date-parts":[[2025,12,10]]}},"alternative-id":["10.1200\/JCO-25-01369"],"URL":"https:\/\/doi.org\/10.1200\/jco-25-01369","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,10]]},"assertion":[{"value":"2025-06-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-19","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}