OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Imetelstat – Rytelo®

DRUG CLASS

Hematologic Agents

COMPLETE LABELING

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NO.	MOLECULAR FORMULA	STRUCTURE
Imetelstat	868169-64-6	Oligonucleotide

ANNOTATED BIBLIOGRAPHY

References updated: 30 September 2024

Abbreviations used: iv, intravenously; MDS, myelodysplastic syndrome.

• FDA. Multi-disciplinary Review. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2024/217779Orig1s000MultidisciplineR.pdf

  (FDA website including product label and multidiscipline review of data submitted in support of imetelstat approval includes discussion of hepatotoxicity, therapy being associated with increase in ALT elevations [43% vs 37% with placebo] and bilirubin [39% vs 39%], with several patients having concurrent elevations in both, but most abnormalities resolved spontaneously suggesting that most elevations were due to the underlying condition; in preregistration studies, there were no instances of clinically apparent liver injury attributed to therapy).
• Tefferi A, Lasho TL, Begna KH, Patnaik MM, Zblewski DL, Finke CM, Laborde RR, et al. A pilot study of the telomerase inhibitor imetelstat for myelofibrosis. N Engl J Med. 2015;373:908-19. [PubMed: 26332545]

  (Among 33 patients with high or intermediate risk myelofibrosis treated with imetelstat [9.4 mg/kg iv] every 1 to 3 weeks, remission was induced in 7 [21%] and adverse events were frequent, especially thrombocytopenia and anemia; ALT elevations arose in 27%, AST in 55%, alkaline phosphatase in 36% and bilirubin in 49% of subjects, but most abnormalities were mild and self-limited and there were no instances of clinically apparent liver injury attributable to imetelstat).
• Baerlocher GM, Oppliger Leibundgut E, Ottmann OG, Spitzer G, Odenike O, McDevitt MA, Röth A, et al. Telomerase inhibitor imetelstat in patients with essential thrombocythemia. N Engl J Med. 2015;373: 920-8. [PubMed: 26332546]

  (Among 18 patients with essential thrombocytosis treated with imetelstat iv once weekly to lower platelet counts to less than 300,000/μL, a hematologic response occurred in all 18, common adverse events were neutropenia, anemia, headache, and syncope; while ALT elevations arose in 72%, they were above 5 times ULN in only 2 [11%]).
• Mascarenhas J, Komrokji RS, Palandri F, Martino B, Niederwieser D, Reiter A, Scott BL, et al. Randomized, single-blind, multicenter phase II study of two doses of imetelstat in relapsed or refractory myelofibrosis. J Clin Oncol. 2021;39:2881-2892. [PubMed: 34138638]

  (Among 107 patients with relapsed or refractory myelofibrosis treated with 2 doses of imetelstat, symptom responses were achieved in 32%, and one year objective responses occurred in 79% and 84%; liver test adverse events occurred in 13%, but there were no instances of clinically apparent drug induced liver injury).
• Santini V. Advances in myelodysplastic syndrome. Curr Opin Oncol. 2021;33:681-6. [PubMed: 34474438]

  (Review of the pathogenesis, clinical features, complications, diagnosis, cytogenetics, and therapy of MDS mentions the use of luspatercept as well as telomerase inhibitors and hypomethylating agents).
• Sekeres MA, Taylor J. Diagnosis and treatment of myelodysplastic syndromes: a review. JAMA. 2022;328:872-880. [PubMed: 36066514]

  (Concise review of clinical features, natural history, diagnosis, and management of MDS; adverse events are listed in tables but without mention or discussion of ALT elevations or hepatotoxicity).
• Garcia-Manero G. Myelodysplastic syndromes: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol. 2023;98:1307-1325. [PubMed: 37288607]

  (Review of the classification of MDS and risk categorization with an update on management including discussion of therapies; no mention of ALT elevations or hepatotoxicity).
• Randall MP, DeZern AE. The management of low-risk myelodysplastic syndromes-current standards and recent advances. Cancer J. 2023;29:152-159. [PubMed: 37195771]

  (Review of treatment of low-risk MDS including use of erythropoietin, iron chelation, lenalidomide, luspatercept, imetelstat, and low dose hypomethylating agents; no discussion of hepatotoxicity).
• Platzbecker U, Santini V, Fenaux P, Sekeres MA, Savona MR, Madanat YF, Díez-Campelo M, et al. Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024;403:249-260. [PubMed: 38048786]

  (Among 178 patients with lower-risk, relapsed or refractory MDS treated with imetelstat vs placebo once weekly, transfusion independence for at least 8 weeks was achieved in 40% vs 15%, while adverse events more common with imetelstat were neutropenia, anemia and thrombocytopenia as well as headache: ALT elevations occurred in 12% vs 7% but were above 5 times ULN in 3% in both groups and there were no clinically apparent episodes of liver injury).