Literature Scan
As seen in TABLE 3 on page 37 , ring sideroblast status , SF3B1 mutation status , and erythropoietin concentration at baseline were associated with HI-E response .
“ Although higher response rates occurred in patients with baseline serum erythropoietin < 200 IU / L , HI-E was also observed in 58 percent of patients with erythropoietin ≥200 [ to ] ≤500 IU / L and 43 percent of patients with erythropoietin > 500 IU / L ,” the researchers wrote , suggesting “ that luspatercept is effective
information ]. See Dosage and Administration ( 2.1 ) in the full prescribing information for dosing recommendations for pediatric patients 1 year and older . The safety and efficacy of PROMACTA in pediatric patients younger than 1 year with ITP have not yet been established .
The safety and efficacy of PROMACTA in pediatric patients with thrombo - cytopenia associated with chronic hepatitis C and severe aplastic anemia have not been established .
8.5 Geriatric Use Of the 106 patients in two randomized clinical trials of PROMACTA 50 mg in chronic ITP , 22 % were 65 years of age and over , while 9 % were 75 years of age and over . In the two randomized clinical trials of PROMACTA in patients with chronic hepatitis C and thrombocytopenia , 7 % were 65 years of age and over , while fewer than 1 % were 75 years of age and over . No overall differences in safety or effectiveness were observed between these patients and younger patients in the placebocontrolled trials , but greater sensitivity of some older individuals cannot be ruled out .
8.6 Hepatic Impairment Hepatic impairment influences the exposure of PROMACTA [ see Clinical Pharmacology ( 12.3 ) in the full prescribing information ].
Reduce the initial dose of PROMACTA in patients with chronic ITP ( adult and pediatric patients 6 years and older only ) or severe aplastic anemia who also have hepatic impairment ( Child-Pugh Class A , B , C ) [ see Dosage and Administration ( 2.1 , 2.3 ) in the full prescribing information , Warnings and Precautions ( 5.2 )]. No dosage adjustment is necessary for patients with chronic hepatitis C and hepatic impairment [ see Clinical Pharmacology ( 12.3 ) in the full prescribing information ].
8.7 Renal Impairment No adjustment in the initial dose of PROMACTA is needed for patients with renal impairment [ see Clinical Pharmacology ( 12.3 ) in the full prescribing information ]. Closely monitor patients with impaired renal function when administering PROMACTA .
8.8 Ethnicity Patients of East Asian ethnicity ( i . e ., Japanese , Chinese , Taiwanese , and Korean ) exhibit higher eltrombopag exposures . A reduction in the initial dose of PROMACTA is recommended for patients of East Asian ancestry with ITP ( adult and pediatric patients 6 years and older only ) or severe aplastic anemia [ see Dosage and Administration ( 2.1 , 2.3 ) in the full prescribing information ]. No dose reduction is needed in patients of East Asian ethnicity with chronic hepatitis C [ see Clinical Pharmacology ( 12.3 ) in the full prescribing information ].
10 OVERDOSAGE In the event of overdose , platelet counts may increase excessively and result in thrombotic / thromboembolic complications .
In one report , a subject who ingested 5,000 mg of PROMACTA had a platelet count increase to a maximum of 929 x 10 9 / L at 13 days following the ingestion . The patient also experienced rash , bradycardia , ALT / AST elevations , and fatigue . The patient was treated with gastric lavage , oral lactulose , intravenous fluids , omeprazole , atropine , furosemide , calcium , dexamethasone , and plasmapheresis ; however , the abnormal platelet count and liver test abnormalities persisted for 3 weeks . After 2 months ’ follow-up , all events had resolved without sequelae .
In case of an overdose , consider oral administration of a metal cationcontaining preparation , such as calcium , aluminum , or magnesium preparations to chelate eltrombopag and thus limit absorption . Closely monitor platelet counts . Reinitiate treatment with PROMACTA in accordance with dosing and administration recommendations [ see Dosage and Administration ( 2.1 , 2.2 ) in the full prescribing information ].
The following are registered trademarks of their respective owners : PEGASYS / Hoffmann-La Roche Inc .; PEGINTRON / Schering Corporation .
Distributed by : Novartis Pharmaceuticals Corporation East Hanover , New Jersey 07936
© Novartis
T2017-32 March 2017 even in patients with higher erythropoietin concentrations , which are associated with poor ESA response .”
No treatment-related deaths were reported during study follow-up . The most common grade 1 / 2 treatment-related adverse events ( AEs ) were fatigue ( n-4 ; 7 %), bone pain ( n = 3 ; 5 %) diarrhea ( n = 3 ; 5 %), myalgia ( n = 2 ; 3 %), headache ( n = 2 ; 3 %), hypertension ( n = 2 ; 3 %), and injection-site erythema ( n = 2 ; 3 %). Three grade 3 treatment-related AEs were reported in three patients ( 5 %), including two reversible events ( myalgia and general physical health deterioration ) and one who had an increase in blast percentages .
The study is limited by its single-arm , openlabel design and the small number of patients in certain subgroups . “ Due to the small number of ring sideroblast – negative patients included [ in ] the study , the likelihood of response to luspatercept cannot be accurately determined in these patients ,” the authors added . Based on data from the present trial , a randomized , placebo-controlled , phase III study of luspatercept in patients with lower-risk , ring sideroblast – positive MDS is ongoing .
“ [ Our results suggest ] that luspatercept is effective even in patients with higher erythropoietin concentrations , which are associated with poor ESA response .”
— UWE PLATZBECKER , MD
The trial was funded by Acceleron Pharma , the manufacturers of luspatercept .
Contributing authors report financial relationships with Acceleron Pharma , Celgene Corporation , Novartis , Bristol-Myers Squibb , and Gilead .
REFERENCE
Platzbecker U , Germing U , Götze KS , et al . Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes ( PACE-MDS ): a multicentre , open-label phase 2 dosefinding study with long-term extension study . Lancet Oncol . 2017 September 1 . [ Epub ahead of print ]
October 2017