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SUSTAINED RESPONSE OFF TREATMENT IN ELTROMBOPAG-TREATED PATIENTS WITH ITP WHO ARE REFRACTORY OR RELAPSED AFTER FIRST-LINE STEROIDS: PRIMARY ANALYSIS OF THE PHASE II TAPER TRIAL
Author(s): ,
Nichola Cooper
Affiliations:
Centre for Haematology, Department of Immunology and Inflammation,Imperial College London, Hammersmith Hospital,London,Royaume-uni;Centre for Haematology, Department of Immunology and Inflammation,Imperial College London, Hammersmith Hospital,London,Vereinigtes Königreich;Centre for Haematology, Department of Immunology and Inflammation,Imperial College London, Hammersmith Hospital,London,Regno Un
,
Waleed Ghanima
Affiliations:
Department of Medicine,Østfold Hospital Trust,Kalnes,Norvège;Department of Medicine,Østfold Hospital Trust,Kalnes,Norwegen;Department of Medicine,Østfold Hospital Trust,Kalnes,Norvegia;Department of Medicine,Østfold Hospital Trust,Kalnes,Norway;Department of Medicine,Østfold Hospital Trust,Kalnes,Noruega;Department of Medicine,Østfold Hospital Trust,Kalnes,Noorwegen;Department of Medicine,Østfold
,
Nicola Vianelli
Affiliations:
Scientific Institute for Research, Hospitalization and Healthcare (IRCCS),Azienda Ospedaliero-Universitaria di Bologna,Bologna,Italie;Scientific Institute for Research, Hospitalization and Healthcare (IRCCS),Azienda Ospedaliero-Universitaria di Bologna,Bologna,Italien;Scientific Institute for Research, Hospitalization and Healthcare (IRCCS),Azienda Ospedaliero-Universitaria di Bologna,Bologna,Ital
,
David Valcárcel
Affiliations:
Department of Hematology,Vall d'Hebron Institute of Oncology (VHIO), University Hospital Vall d'Hebron,Barcelona,Espagne;Department of Hematology,Vall d'Hebron Institute of Oncology (VHIO), University Hospital Vall d'Hebron,Barcelona,Spanien;Department of Hematology,Vall d'Hebron Institute of Oncology (VHIO), University Hospital Vall d'Hebron,Barcelona,Spagna;Department of Hematology,Vall d'Hebron
,
İrfan Yavaşoğlu
Affiliations:
Department of Hematology,Adnan Menderes University,Aydın,Turquie;Department of Hematology,Adnan Menderes University,Aydın,Türkei;Department of Hematology,Adnan Menderes University,Aydın,Turchia;Department of Hematology,Adnan Menderes University,Aydın,Turkey;Department of Hematology,Adnan Menderes University,Aydın,Turquía;Department of Hematology,Adnan Menderes University,Aydın,Turkije;Department o
,
Anait Melikyan
Affiliations:
National Research Center for Hematology,Moscow,Russie, Fédération De;National Research Center for Hematology,Moscow,Russia;National Research Center for Hematology,Moscow,Russia;National Research Center for Hematology,Moscow,Russische Federatie;National Research Center for Hematology,Moscow,Rússia;National Research Center for Hematology,Moscow,Россия
,
Eduardo Yañez Ruiz
Affiliations:
Hematology-Oncology Unit, Department of Internal Medicine, School of Medicine,Universidad de la Frontera,Temuco,Chili;Hematology-Oncology Unit, Department of Internal Medicine, School of Medicine,Universidad de la Frontera,Temuco,Chile;Hematology-Oncology Unit, Department of Internal Medicine, School of Medicine,Universidad de la Frontera,Temuco,Cile;Hematology-Oncology Unit, Department of Interna
,
Jens Haenig
Affiliations:
Novartis Pharma AG,Basel,Suisse;Novartis Pharma AG,Basel,Schweiz;Novartis Pharma AG,Basel,Svizzera;Novartis Pharma AG,Basel,Switzerland;Novartis Pharma AG,Basel,Suiza;Novartis Pharma AG,Basel,Zwitserland;Novartis Pharma AG,Basel,Suíça;Novartis Pharma AG,Basel,Швейцария ;Novartis Pharma AG,Basel,Schweiz
,
James Lee
Affiliations:
Novartis Pharmaceuticals Corporation,East Hanover, NJ,États-unis;Novartis Pharmaceuticals Corporation,East Hanover, NJ,Vereinigte Staaten;Novartis Pharmaceuticals Corporation,East Hanover, NJ,Stati Uniti;Novartis Pharmaceuticals Corporation,East Hanover, NJ,United States;Novartis Pharmaceuticals Corporation,East Hanover, NJ,Estados Unidos;Novartis Pharmaceuticals Corporation,East Hanover, NJ,Veren
,
Joan Maier
Affiliations:
Novartis Pharma AG,Basel,Suisse;Novartis Pharma AG,Basel,Schweiz;Novartis Pharma AG,Basel,Svizzera;Novartis Pharma AG,Basel,Switzerland;Novartis Pharma AG,Basel,Suiza;Novartis Pharma AG,Basel,Zwitserland;Novartis Pharma AG,Basel,Suíça;Novartis Pharma AG,Basel,Швейцария ;Novartis Pharma AG,Basel,Schweiz
,
Nikita Zolkin
Affiliations:
IQVIA,St. Petersburg,Russie, Fédération De;IQVIA,St. Petersburg,Russia;IQVIA,St. Petersburg,Russia;IQVIA,St. Petersburg,Russische Federatie;IQVIA,St. Petersburg,Rússia;IQVIA,St. Petersburg,Россия
Francesco Zaja
Affiliations:
Department of Medical, Surgical and Health Sciences,University of Trieste,Trieste,Italie;Department of Medical, Surgical and Health Sciences,University of Trieste,Trieste,Italien;Department of Medical, Surgical and Health Sciences,University of Trieste,Trieste,Italia;Department of Medical, Surgical and Health Sciences,University of Trieste,Trieste,Italy;Department of Medical, Surgical and Health S
(Abstract release date: 05/12/22) EHA Library. Cooper N. 06/11/22; 357156; S292
Dr. Nichola Cooper
Dr. Nichola Cooper
Contributions
Abstract
Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S292

Type: Oral Presentation

Session title: Thrombocytopenia - Management insights in ITP and TTP

Background

Corticosteroids (CSs) are the standard 1st-line treatment for primary immune thrombocytopenia (ITP); however, long-term CS use is associated with high relapse rates and considerable toxicity. Treatments that achieve a sustained response and reduce the need for long-term CS use are needed. Eltrombopag (EPAG) is a thrombopoietin receptor agonist (TPO-RA) indicated in Europe for the treatment of patients (pts) aged ≥1 year with primary ITP lasting ≥6 months who are refractory to other treatments (eg, CSs). Evidence suggests that a proportion of pts treated with TPO-RAs achieve sustained responses that are maintained after TPO-RA tapering and discontinuation; however, much of the evidence is retrospective with only a few prospective studies investigating sustained response off treatment (SRoT).

Aims

TAPER (NCT03524612), a Phase II, open-label, prospective, single-arm study, aims to determine whether EPAG can induce SRoT in pts with ITP after 1st-line CS failure.

Methods

Adult (≥18 years) pts with ITP who did not respond to or had relapsed after initial CS therapy, with platelet counts <30×109/L and assessed as needing treatment, were included. Patients received a 50 mg/day starting dose of EPAG (25 mg/day for East/Southeast Asian pts; 12.5 mg/day for Japanese pts in Japan), which could be increased up to 75 mg/day (50 mg/day in Japan) if needed. The primary endpoint was the number (%) of pts with SRoT by Month 12; SRoT was defined as achieving a complete response (CR, ie, platelet count ≥100×109/L), then maintaining a stable platelet count (no counts <70×109/L) for 2 months, followed by successful EPAG tapering and discontinuation with platelet counts ≥30×109/L and no bleeding events or rescue therapy. Patients with SRoT at Month 12 were followed for a further year. Secondary outcomes included SRoT duration and platelet count changes from baseline. Data to Month 12 are presented.

Results

N=105 pts were enrolled. The median (interquartile range [IQR]) age was 46 (30-65) years; 61% were female. In the 1st 12 months, median (IQR) duration of exposure to EPAG was 5.6 (2.3-11.9) months and median (IQR) EPAG dose was 57.1 (37.5-69.0) mg/day. Overall, 89 pts (85%) achieved CR at least once and 65 pts (62%) maintained a platelet count ≥70×109/L for 2 months after CR. EPAG tapering and discontinuation was achieved in 44 pts (42%). The primary endpoint was met, with 32 pts (30.5% [95% confidence interval, 21.9-40.2]; P<0.001 [H1: P>15%; alpha: 0.05]) achieving SRoT until Month 12 (Fig. 1); SRoT was maintained from last dose to Month 12 for a median (IQR) of 33.3 (25.7-45.3) weeks. The median (IQR) absolute increase in platelet counts from baseline at Month 12 was 77.0×109/L (35.0-145.0). All-grade adverse events (AEs) occurred in 92/105 (88%) pts (grade ≥3 AEs: 33/105 [31%]). Treatment-related AEs occurred in 37 (35%) pts (8 [7.6%] grade ≥3). The most common all-grade AEs were headache (21% of pts with ≥1 event [grade ≥3: 1% of all pts]), thrombocytopenia (17% [10.5%]), and petechiae (11% [1%]). There were 4 deaths (none were considered treatment related): 3 were on-treatment (central nervous system hemorrhage [n=1], intracranial hemorrhage [n=1], metastases to peritoneum [n=1]) and 1 death (malignant neoplasm) occurred 238 days after last dose.

Conclusion

Data from the TAPER study indicate that a significant proportion of pts experience sustained response following tapering and discontinuation of EPAG, even after a relatively short duration of exposure. Overall EPAG was well tolerated with no unexpected AEs.

Keyword(s): Adult, ITP, Thrombocytopenia, Thrombopoietin (TPO)

Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S292

Type: Oral Presentation

Session title: Thrombocytopenia - Management insights in ITP and TTP

Background

Corticosteroids (CSs) are the standard 1st-line treatment for primary immune thrombocytopenia (ITP); however, long-term CS use is associated with high relapse rates and considerable toxicity. Treatments that achieve a sustained response and reduce the need for long-term CS use are needed. Eltrombopag (EPAG) is a thrombopoietin receptor agonist (TPO-RA) indicated in Europe for the treatment of patients (pts) aged ≥1 year with primary ITP lasting ≥6 months who are refractory to other treatments (eg, CSs). Evidence suggests that a proportion of pts treated with TPO-RAs achieve sustained responses that are maintained after TPO-RA tapering and discontinuation; however, much of the evidence is retrospective with only a few prospective studies investigating sustained response off treatment (SRoT).

Aims

TAPER (NCT03524612), a Phase II, open-label, prospective, single-arm study, aims to determine whether EPAG can induce SRoT in pts with ITP after 1st-line CS failure.

Methods

Adult (≥18 years) pts with ITP who did not respond to or had relapsed after initial CS therapy, with platelet counts <30×109/L and assessed as needing treatment, were included. Patients received a 50 mg/day starting dose of EPAG (25 mg/day for East/Southeast Asian pts; 12.5 mg/day for Japanese pts in Japan), which could be increased up to 75 mg/day (50 mg/day in Japan) if needed. The primary endpoint was the number (%) of pts with SRoT by Month 12; SRoT was defined as achieving a complete response (CR, ie, platelet count ≥100×109/L), then maintaining a stable platelet count (no counts <70×109/L) for 2 months, followed by successful EPAG tapering and discontinuation with platelet counts ≥30×109/L and no bleeding events or rescue therapy. Patients with SRoT at Month 12 were followed for a further year. Secondary outcomes included SRoT duration and platelet count changes from baseline. Data to Month 12 are presented.

Results

N=105 pts were enrolled. The median (interquartile range [IQR]) age was 46 (30-65) years; 61% were female. In the 1st 12 months, median (IQR) duration of exposure to EPAG was 5.6 (2.3-11.9) months and median (IQR) EPAG dose was 57.1 (37.5-69.0) mg/day. Overall, 89 pts (85%) achieved CR at least once and 65 pts (62%) maintained a platelet count ≥70×109/L for 2 months after CR. EPAG tapering and discontinuation was achieved in 44 pts (42%). The primary endpoint was met, with 32 pts (30.5% [95% confidence interval, 21.9-40.2]; P<0.001 [H1: P>15%; alpha: 0.05]) achieving SRoT until Month 12 (Fig. 1); SRoT was maintained from last dose to Month 12 for a median (IQR) of 33.3 (25.7-45.3) weeks. The median (IQR) absolute increase in platelet counts from baseline at Month 12 was 77.0×109/L (35.0-145.0). All-grade adverse events (AEs) occurred in 92/105 (88%) pts (grade ≥3 AEs: 33/105 [31%]). Treatment-related AEs occurred in 37 (35%) pts (8 [7.6%] grade ≥3). The most common all-grade AEs were headache (21% of pts with ≥1 event [grade ≥3: 1% of all pts]), thrombocytopenia (17% [10.5%]), and petechiae (11% [1%]). There were 4 deaths (none were considered treatment related): 3 were on-treatment (central nervous system hemorrhage [n=1], intracranial hemorrhage [n=1], metastases to peritoneum [n=1]) and 1 death (malignant neoplasm) occurred 238 days after last dose.

Conclusion

Data from the TAPER study indicate that a significant proportion of pts experience sustained response following tapering and discontinuation of EPAG, even after a relatively short duration of exposure. Overall EPAG was well tolerated with no unexpected AEs.

Keyword(s): Adult, ITP, Thrombocytopenia, Thrombopoietin (TPO)

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