Rytelo Drug Information
Generic name: IMETELSTAT SODIUM
Uses of Rytelo
1. INDICATIONS AND USAGE RYTELO is indicated for the treatment of adult patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia requiring 4 or more red blood cell units over 8 weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESA). RYTELO is an oligonucleotide telomerase inhibitor indicated for the treatment of adult patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia requiring 4 or more red blood cell units over 8 weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESA).
Dosage & Administration of Rytelo
| First dose reduction | 5.6 mg/kg |
|---|---|
| Second dose reduction | 4.4 mg/kg |
Side Effects of Rytelo
Musculoskeletal and connective tissue disorders Arthralgia/myalgia Arthralgia/myalgia: arthralgia, back pain, bone pain
musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, pain, pain in extremity, pain in jaw, and pelvic pain. 25 2.5 19 5 Infections and infestations COVID-19 COVID-19: asymptomatic COVID-19, COVID-19, COVID-19 pneumonia, and SARS-CoV-2 antibody test positive. 19 1.7 14 5 Urinary tract infection Urinary tract infection: cystitis, Escherichia urinary tract infection, renal abscess, and urinary tract infection. 9 2.5 7 0 Nervous system disorders Headache 13 0.8 5 0 Syncope Syncope: fall, pre-syncope, and syncope. 7 1.7 1.7 0 Immune system disorders Infusion-related reactions Infusion-related reactions: abdominal pain, arthralgia, asthenia, back pain, bone pain, diarrhea, erythema, headache, hypertensive crisis, malaise, non-cardiac chest pain, pruritus, and urticaria. Only events considered related to infusion-related reactions are included. 8 1.7 3.4 0 Respiratory, thoracic and mediastinal disorders Epistaxis 7 0 0 0 Vascular disorders Hematoma 6 0 0 0 Skin and subcutaneous tissue disorders Pruritus 6 0 1.7 0 Cardiac disorders Atrial arrhythmia Atrial arrhythmia: atrial fibrillation and atrial flutter. 6 1.7 3.4
Injury, poisoning and procedural complications Fractures Fractures: femur fracture, hand fracture, hip
fracture, humerus fracture, lumbar vertebral fracture, and thoracic vertebral fracture. 5 3.4 1.7
Clinically relevant adverse reactions in < 5% of patients who received
RYTELO included febrile neutropenia, sepsis, gastrointestinal hemorrhage, and hypertension. Table 6 summarizes the laboratory abnormalities in IMerge. Table 6: Select Laboratory Abnormalities (≥10%) That Worsened from Baseline in Patients with MDS Who Received RYTELO with a Difference Between Arms of >2% Compared to Placebo in IMerge Laboratory Abnormality RYTELO The denominator used to calculate the rate varied from 97 to 118 based on the number of patients with a baseline value and at least one post-treatment value.
Placebo The denominator used to calculate the rate varied from 50 to 59 based on the number of patients with a baseline value and at least one post-treatment value. All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03. ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; PTT = partial thromboplastin time Hematology Platelet count decreased 97 65 34 8 White blood cell count decreased 94 53 59
Neutrophil count decreased 92 72 47 7
PTT prolonged 26 1 18 4 Chemistry AST increased 53 0.8 22
ALP increased 48 0 12 0
ALT increased 43 3.4 37 5
Warnings & Cautions for Rytelo
5. WARNINGS AND PRECAUTIONS Thrombocytopenia : Grade 3 and Grade 4 thrombocytopenia occurred; obtain complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, and prior to each cycle thereafter to monitor. Delay or dose reduce as recommended. Neutropenia : Grade 3 and Grade 4 neutropenia occurred; obtain complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, and prior to each cycle thereafter to monitor.
Delay or dose reduce as recommended. Infusion-Related Reactions : Premedicate before infusion. Interrupt, decrease the rate of infusion, or permanently discontinue RYTELO based on severity.
Embryo-Fetal Toxicity : Can cause embryo-fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception. 5.1. Thrombocytopenia RYTELO can cause thrombocytopenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased platelets occurred in 65% of patients with MDS treated with RYTELO . Median time to onset of first occurrence of Grade 3 or 4 decreased platelets was 6 weeks (range: 2 to 88 weeks) and median time to recovery from each occurrence of Grade 3 or 4 decreased platelets to Grade 2 or lower, or last value available, was 1.3 weeks (range: 0.1 to 13 weeks). Grade 3 or 4 decreased platelets occurred throughout treatment with RYTELO, with 48% of patients experiencing Grade 3 or Grade 4 thrombocytopenia during cycles 1-3, 31% during cycles 4-6, 33% during cycles 7-12, and 24% during cycles 13 and beyond.
Grade 3 or 4 bleeding was seen in 2.5% of patients, including gastrointestinal bleeding (1.7%) and hematuria (0.8%). Monitor patients with thrombocytopenia for bleeding. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer platelet transfusions as appropriate.
Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended . 5.2. Neutropenia RYTELO can cause neutropenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased neutrophils occurred in 72% of patients with MDS treated with RYTELO . Median time to onset of first occurrence of Grade 3 or 4 decreased neutrophils was 4.6 weeks (range: 1 to 81 weeks) and median time to recovery from each occurrence of Grade 3 or 4 decreased neutrophils to Grade 2 or lower, or last value available, was 1.9 weeks (range: 0 to 16 weeks). Grade 3 or 4 decreased neutrophils occurred throughout treatment with RYTELO, with 65% of patients experiencing Grade 3 or Grade 4 neutropenia during cycles 1-3, 35% during cycles 4-6, 32% during cycles 7-12, and 39% during cycles 13 and beyond. Febrile neutropenia occurred in 0.8% and sepsis in 4.2%. Monitor patients with Grade 3 or 4 neutropenia for infections, including sepsis.
Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer growth factors and anti-infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended . 5.3. Infusion-Related Reactions RYTELO can cause infusion-related reactions.
In the clinical trial, infusion-related reactions occurred in 8% of patients with MDS treated with RYTELO; Grade 3 or 4 infusion-related reactions occurred in 1.7%, including hypertensive crisis (0.8%). The most common infusion-related reaction was headache (4.2%). Infusion-related reactions usually occur during or shortly after the end of the infusion. Premedicate patients at least 30 minutes prior to infusion with diphenhydramine and hydrocortisone as recommended and monitor patients for at least one hour following the infusion as recommended. Manage symptoms of infusion-related reactions with supportive care and infusion interruptions, decrease infusion rate, or permanently discontinue as recommended . 5.4. Embryo-Fetal Toxicity Based on findings in animals, RYTELO can cause embryo-fetal harm when administered to a pregnant woman.
In animal reproduction studies, administration of imetelstat to pregnant mice during the period of organogenesis resulted in embryo-fetal mortality at maternal exposures (AUC) 2.5-times the human exposure at the recommended clinical dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with RYTELO and for 1 week after the last dose .
Pregnancy Safety for Rytelo
8.1. Pregnancy Risk Summary Based on findings in animal studies, RYTELO can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on RYTELO use in pregnant women to evaluate for drug-associated risk. In embryo-fetal developmental toxicity studies, administration of imetelstat to pregnant mice and rabbits during the period of organogenesis resulted in embryo-fetal mortality, which in mice occurred at maternal exposures approximately 2.5 times the human exposure at the recommended clinical dose.
Advise pregnant women of the potential risk to a fetus . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In embryo-fetal developmental toxicity studies, imetelstat was administered by IV bolus injection at doses of 4.7, 9.4, 14.1 or 28.2 mg/kg/day on gestation days 6, 9, and 12 in mice, or by 2-hour intravenous infusion at doses of 4.7, 14.1, or 28.2 mg/kg on gestation days 6 and 13 in rabbits. In rabbits, the dose of 28.2 mg/kg was maternally toxic.
Increased post-implantation loss due to an increase in early resorptions, resulting in a decrease in viable fetuses and litter was noted in mice at 28.2 mg/kg and in rabbits starting at 14.1 mg/kg; corresponding to exposures (based on AUC) that are approximately 2.5-times (mice) or 9.3-times (rabbits) the human exposure at the recommended clinical dose.
Pediatric Use of Rytelo
8.4. Pediatric Use Safety and effectiveness of RYTELO in pediatric patients have not been established.
Contraindications for Rytelo
4. CONTRAINDICATIONS None. None.
Clinical Studies of Rytelo
ECOG Score, n (%) 0: Asymptomatic 42 21 1: Symptomatic fully ambulatory
70 39 2: Symptomatic in bed less than 50% of the day 6 0 IPSS Risk Classification, n (%) Low 80 39 Intermediate-1 38 21 Prior RBC transfusion burden Prior RBC transfusion burden is defined as the maximum number of RBC units transfused over an 8-week period during the 16 weeks prior to randomization., n (%) 4 to 6 units 62 33 > 6 units 56 27 WHO Classification, n (%) RS+ RS+ includes refractory anemia with ring sideroblasts (RARS)/refractory cytopenia with multilineage dysplasia and ≥ 15% ringed sideroblasts (RCMD-RS). 73 37 RS˗ RS˗ includes others. 44 23 Missing 1 0 Baseline sEPO, n (%) ≤ 500 mU/mL 87 36 > 500 mU/mL 26 22 Missing 5 2 Prior ESA Use, n (%) Yes 108 52 No 10 8 Baseline blood counts, median Neutrophils (cells/L) 2.6 × 10 9 2.7 × 10 9 Hemoglobin (g/dL) 7.9
Platelets (cells/L) 230 × 10 9 230 × 10 9 Efficacy was
established after a median follow up time of 19.5 months (range: 1.4 to 36.2) in the imetelstat group and 17.5 months (range: 0.7 to 34.3) in the placebo group based upon the proportion of patients who achieved ≥ 8-week and ≥ 24-week RBC-TI, defined as the absence of RBC transfusion(s) during any consecutive 8-week (56-day) period, and during any consecutive 24-week (168-day) period, respectively, from randomization until the start of subsequent anti-cancer therapy (if any). The efficacy results are summarized in Table 8. Table 8: Efficacy Results of RYTELO in IMerge RYTELO (N=118) Placebo (N=60) % Difference (95% CI) 95% CI based on Wilson Score method. p -value p- value is based on Cochran-Mantel-Haenszel (CMH) controlling for prior RBC transfusion burden (≤ 6 versus >6 units RBC) and IPSS risk group (low versus intermediate-1) applied to randomization. Abbreviations: CI = Confidence Interval; RBC = Red Blood Cell; TI = Transfusion Independence Rate of ≥ 8-week RBC TI ≥ 8-week RBC TI, n (%) 47 9 24.8 < 0.001 95% CI for response rate (%) Exact Clopper-Pearson confidence interval. Rate of ≥ 24-week RBC TI ≥ 24-week RBC TI, n (%) 33 2 24.6 95% CI for response rate (%) < 0.001
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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