scholarly journals Durability of Platelet Response When Switching from Eltrombopag or Romiplostim to Avatrombopag in Immune Thrombocytopenia (ITP): A Multicenter Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1015-1015
Author(s):  
Hanny Al-Samkari ◽  
Debbie Jiang ◽  
Terry B. Gernsheimer ◽  
Howard A. Liebman ◽  
Susie Lee ◽  
...  
Keyword(s):  
Adverse Event ◽  
Platelet Count ◽  
Research Funding ◽  
Immune Thrombocytopenia ◽  
Rescue Therapy ◽  
Initial Response ◽  
Boxed Warning ◽  
Platelet Response ◽  
Platelet Counts ◽  
Loss Of Response

Abstract BACKGROUND : Thrombopoietin receptor agonists (TPO-RAs) are widely utilized second-line treatments for immune thrombocytopenia (ITP). The TPO-RAs eltrombopag and romiplostim have been FDA approved for over a decade with established efficacy and safety profiles. Avatrombopag is a newer oral TPO-RA approved in 2019 for ITP. Avatrombopag was efficacious in raising platelet counts in clinical trials, and it has an exposure-adjusted safety profile generally comparable to placebo with no boxed warning for hepatotoxicity as does eltrombopag. Also unlike eltrombopag, avatrombopag does not chelate polyvalent cations; therefore, it is administered with food and without restrictions regarding meal composition. A high proportion of patients (~90%) respond to avatrombopag; however, data describing the durability of platelet response on avatrombopag following treatment with other TPO-RAs is limited. AIMS : Understand the time until patients treated with avatrombopag experienced their first loss of response, if any, and their percent of time with a response following switch from eltrombopag or romiplostim. METHODS : We retrospectively evaluated all adults with ITP who switched from eltrombopag or romiplostim to avatrombopag at four U.S. tertiary ITP referral centers from July 2019 through December 2020. Reason for switching from eltrombopag or romiplostim (ineffectiveness, adverse event, convenience) was collected. Patients were treated with avatrombopag for at least two months to evaluate effectiveness. Response was defined as a platelet count ≥30,000/uL. Loss of response was defined as two consecutive platelet counts at least 7 days apart <30,000/uL. In these analyses, platelet counts were disqualified if <8 weeks from receipt of rescue corticosteroids or <4 weeks from intravenous immunoglobulin. RESULTS: 44 patients were included, with a median (range) age of 60 (21-87) years; 55% were female. At avatrombopag initiation, patients had an ITP diagnosis for a mean of 8.1 years with a mean of 4.8 unique prior ITP therapies. 42/44 (95%) of patients responded to avatrombopag at least once and 36/44 (81.8%) responded without the need for rescue therapy. 6/44 (13.6%) responded to avatrombopag and required at least one rescue therapy during exposure. 31/42 (73.8%) of patients never experienced a loss of response. All patients who responded to avatrombopag maintained response for 88.7% of their time on treatment. Patients who responded without the need for rescue therapy maintained their response for 93.6% of their time on avatrombopag. Patients who switched for convenience maintained a response for 96.5% of the time on avatrombopag. Patients who switched for adverse events maintained a response for 90.2% of the time. Patients who switched for efficacy maintained a response for 68.2% of the time. Overall, the median platelet count for all avatrombopag exposure was 107×10 9/L. The median platelet count for convenience switchers was 129×10 9/L, efficacy switchers was 60×10 9/L, and adverse event switchers was 93×10 9/L. CONCLUSION: In a heavily pretreated chronic ITP population who switched from another TPO-RA to avatrombopag, the initial response to avatrombopag was both durable (with up to 74% of patients never experiencing a loss of response) and stable (with patients maintaining a response on average for up to 89% of the time). Figure 1 Figure 1. Disclosures Al-Samkari: Argenx: Consultancy; Dova/Sobi: Consultancy, Research Funding; Novartis: Consultancy; Amgen: Research Funding; Rigel: Consultancy; Agios: Consultancy, Research Funding; Moderna: Consultancy. Gernsheimer: Principia: Research Funding; Rigel: Research Funding; Amgen: Honoraria; Novartis: Honoraria; Cellphire: Consultancy; Dova: Consultancy; Sanofi: Consultancy. Liebman: Pfizer: Consultancy; Dova: Consultancy, Honoraria; Argenx: Research Funding; Amgen: Consultancy; Sanofi/Genzyme: Research Funding; Novartis: Consultancy, Research Funding. Lee: Dova: Honoraria. Bernheisel: Sobi, Inc.: Current Employment. Kolodny: Sobi, Inc.: Current Employment. Wojdyla: Sobi, Inc.: Current Employment. Vredenburg: Sobi, Inc.: Current Employment. Jamieson: Sobi, Inc.: Current Employment. Cuker: Takeda: Research Funding; Sanofi: Research Funding; Spark Therapeutics: Research Funding; Pfizer: Research Funding; Novo Nordisk: Research Funding; Novartis: Research Funding; Bayer: Research Funding; Alexion: Research Funding; UpToDate: Patents & Royalties; Synergy: Consultancy.

scholarly journals Long Term Discontinuation of Eltrombopag after Remission in Primary Immune Thrombocytopenia: 8-Year Follow-up Data from 15 Spanish Centers

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2352-2352
Author(s):  
Tomas Jose Gonzalez-Lopez ◽  
Fernando Fernandez-Fuertes ◽  
Maria Cristina Pascual Izquierdo ◽  
Isabel Caparros ◽  
Silvia Bernat ◽  
...  
Keyword(s):  
Platelet Count ◽  
Median Time ◽  
Research Funding ◽  
Immune Thrombocytopenia ◽  
Previous Treatment ◽  
Complete Response ◽  
Platelet Response ◽  
Platelet Counts

Background: Successful discontinuation of eltrombopag in certain immune thrombocytopenia (ITP) patients after complete response has already been demonstrated. However, the frequency of this phenomenon and type of candidate patients are still matter of discussion. Moreover, possibility of long term discontinuation responses is not clearly established. Methods: Here we retrospectively evaluated our whole cohort of 508 adult patients (aged 18 years or more) with primary ITP treated with eltrombopag included in the Spanish Eltrombopag Registry with a focus on the patients who achieved a durable (at least six months) platelet response after stopping eltrombopag. Successful discontinuation of eltrombopag (SDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 6 months in absence of eltrombopag or any rescue therapies administered. Long term discontinuation of eltrombopag (LTDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 36 months in the absence of eltrombopag or any rescue therapies administered. The study was approved by the Hospital Universitario de Burgos Ethics Committee and fulfilled Helsinki declaration standards. Results: While 37.4% of our patients relapsed of ITP with subsequent platelet count drop sometime during first six months of discontinuation of eltrombopag, a total of 74 patients (14.6%) were able to achieve SDOE. The median age of SDOE patients was 62 [range, 47-79] years. There were 47 women and 27 men. According to the standard definition, patients were allocated to newly diagnosed (n=17), persistent (n=15) and chronic (n=42) ITP groups. The median time from diagnosis to eltrombopag initiation was 31 [range, 4-104] months. The median number of previous therapies was 2 [range, 1-2], including splenectomy (14%), rituximab (18%) and romiplostim (12%). As expected, all patients but 1 achieved a complete response (platelet count ≥100 x 109/L) prior to eltrombopag discontinuation The median duration of eltrombopag treatment was 7 [range, 2-19] months. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n=43), platelet count >400x109/L (n=16), aspartate aminotransferase elevation (n=5), diarrhea (n=4), thrombosis (n=3), patient's request (n=2) and other reasons (n=1). Analysis of these SDOE discontinued patients show that with a median follow-up of 55 [range, 29-79] months, 38 patients (51.3%) maintained treatment-free response 36 months after stopping eltrombopag with no need of additional ITP therapies (median time of eltrombopag discontinuation was 70 [range, 50-77] months).This condition is what we define now as LTDOE. Nevertheless, 36 patients relapsed beyond 6 months but before 36 months of eltrombopag discontinuation (median time of eltrombopag discontinuation was 10 [range,7 -22] months). Characteristics of LTDOE population were a median time since ITP diagnosis of 32 [range, 5-88] months with 15/38 patients having ITP <1 year. 9 patients (24%) were male and their median age was 50 [range, 37-64] years. They had received a median of only two previous treatment lines [range: 1-2 lines]. The median platelet count before starting eltrombopag was 19 x 109/L [range, 8-40]. Meanwhile, platelet count before eltrombopag stop was 218 x 109/L [range, 123-356]. The main characteristics (age, gender, duration of ITP, prior ITP lines, platelet count before starting eltrombopag, duration of eltrombopag treatment, and platelet count before eltrombopag withdrawal) of the 38 patients with LTDOE were compared with those of the SDOE cohort who did not achieve a LTDOE. Unfortunately, no predictive factors of LTDOE could be identified. Conclusion: Durable platelet response following eltrombopag cessation may be observed in only 15% of primary ITP patients treated with this drug. On the contrary, half of patients who achieve a sustained response after eltrombopag withdrawal will get a long term discontinuation. However, we are lacking predictor factors for successful and long-term discontinuation of eltrombopag in primary ITP. Disclosures Gonzalez-Lopez: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Pascual Izquierdo:Novartis: Consultancy; Sanofi: Consultancy. Sánchez-González:Amgen: Consultancy, Speakers Bureau; Gilead: Speakers Bureau; Navartis: Consultancy, Speakers Bureau; Shire: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Jarque:Takeda: Consultancy, Speakers Bureau; Shire: Consultancy, Speakers Bureau; Shionogi: Consultancy, Speakers Bureau; Servier: Speakers Bureau; Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Grifols: Consultancy; Gilead: Consultancy, Speakers Bureau; CellTrion: Consultancy; Celgene: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Abbie: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau.

Durability of Initial Platelet Count Response in Patients Treated with Avatrombopag for Immune Thrombocytopenia (ITP): Post-Hoc Results from a Phase 3 Clinical Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-23
Author(s):  
Shivi Jain ◽  
Matthew Wojdyla ◽  
Michael Vredenburg ◽  
Brian Jamieson ◽  
Terry B. Gernsheimer
Keyword(s):  
Research Funding ◽  
Rescue Medication ◽  
Rescue Therapy ◽  
Initial Response ◽  
Median Number ◽  
Boxed Warning ◽  
Phase 3 ◽  
Response Level ◽  
Loss Of Response ◽  
Post Hoc

Background: The clinical management of ITP has been evolving. Thrombopoietin receptor agonists (TPO-RAs) have become widely utilized as subsequent treatments, and the 2019 ASH guidelines recommend their use over rituximab to achieve a durable response. TPO-RAs eltrombopag (ELT) and romiplostim (ROMI) have been FDA approved for over a decade with a well demonstrated efficacy profile. ELT, an oral medication, must be administered two hours prior to or four hours after meals containing polyvalent cations such as calcium or magnesium to mitigate clinically relevant effects on the pharmacokinetic profile (ELT prescribing information). Additionally, ELT carries a boxed warning for hepatoxicity that requires monitoring. ROMI, an injectable, is typically administered in a health care practitioner's office weekly which may be challenging for some patients (Pts). Avatrombopag (AVA) is an oral TPO-RA approved in 2019 for Pts with ITP. In clinical trials, AVA rapidly increased platelet count (PC) (5 days) and maintained it in the target range (50 to 150×109/L) with chronic dosing. Further, it has an exposure-adjusted safety profile generally comparable to placebo with no boxed warning for hepatotoxicity. AVA does not chelate polyvalent cations; therefore, it is administered with food and without restrictions regarding meal composition. A high proportion of Pts (~90%) respond to AVA; but limited information is available regarding the durability of response over time utilizing clinically relevant loss of response definitions. Aims: To understand the duration of initial response with AVA and the overall percent of treatment days a response level PC was achieved in responding Pts. Methods: A 6-month, multicenter, randomized, double-blind, Phase 3 study enrolled 32 AVA and 17 placebo-treated Pts with ITP. The study design included a 6-week study drug titration period, 12-week concomitant ITP medication reduction period, and an 8-week maintenance period. The primary endpoint was the median number of cumulative weeks of PC response (PC ≥50,000/µL) over the course of the study without rescue medication. Pts receiving rescue medication during the study were deemed to be non-responders for the remainder of the study. For this post-hoc analysis, we analyzed how many days it took for responding AVA Pts (n=29) to experience their first loss of response (LOR) or reach core study conclusion. After the initial PC ≥50,000/µL was noted, we also examined the percentage of remaining treatment time that initial response was maintained. Response was defined as the first time achieving a PC ≥50,000/µL. LOR was defined as a Pt experiencing a PC &lt;30,000/µL for 4 consecutive weeks (LOR-4wk), or in a more conservative manner, Pts experiencing a PC &lt;30,000/µL on 2 consecutive scheduled visits (LOR-2vis) [visits were weekly or biweekly depending on the phase of the study with 21 visits occurring over 26 weeks]. When a LOR was observed, the date of the first PC &lt;30,000/µL was used for subsequent calculations with a return of response defined as a PC exceeding ≥30,000/µL again. Pts who required rescue therapy (n=6) were included in the analyses and the first date of administration was used for the LOR date. Pts requiring either corticosteroids (n=4) or IVIg (n=1) as rescue therapy were considered non-responders for a minimum of 8 weeks and Pts receiving a platelet transfusion (n=1) for a minimum of 1 week. Results: 72.4% (21/29) and 55.2% (16/29) of AVA responsive Pts never experienced a LOR-4wk or LOR-2vis, respectively. The median number of days until responding Pts experienced their first LOR-4wk, discontinued treatment, or completed the 6-month study was 170 (mean 134.7) and 146 (mean 119.1) for the LOR-2vis analysis. Pts maintained their initial response on average for 87.7% (median 100%) of their remaining time in the study for LOR-4wk and 84.5% (median 100%) for LOR-2vis analyses, with Pts often losing response only briefly when noted. Pts requiring rescue therapy often returned to a response level PC and remained in the 6-month study for approximately 5 months following their initial response. Conclusions: These data suggest that the initial response to AVA is stable and durable with up to 72.4% of Pts never experiencing a LOR, even with the planned objective of reducing the use of baseline concomitant ITP medications during the study. In those pts experiencing a LOR, many ended up achieving response level PCs again without a subsequent LOR. Disclosures Wojdyla: Dova Pharmaceuticals: Current Employment. Vredenburg:Dova Pharmaceuticals: Current Employment. Jamieson:Dova Pharmaceuticals: Current Employment. Gernsheimer:Amgen Corporation: Consultancy, Honoraria; Novartis: Consultancy; Cellphire: Consultancy; Rigel Corporation: Consultancy, Research Funding; Principia: Research Funding; Sanofi: Consultancy; Vertex: Consultancy; Dova Pharmaceuticals: Consultancy.

Final Results from an International, Multi-Center, Single-Arm Study Evaluating the Safety and Efficacy of Romiplostim in Adults with Primary Immune Thrombocytopenia (ITP),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3279-3279 ◽  
Author(s):  
Ann Janssens ◽  
Michael D. Tarantino ◽  
Robert Bird ◽  
Maria Gabriella Mazzucconi ◽  
Ralph Vincent V. Boccia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Platelet Response ◽  
Employment Equity ◽  
Advisory Committees ◽  
Platelet Production ◽  
Platelet Counts ◽  
Equity Ownership

Abstract Abstract 3279 Background: ITP is an autoimmune disorder characterized by increased platelet destruction and suboptimal platelet production. Romiplostim stimulates platelet production via the TPO-receptor, and is recommended for second- and third-line treatment of chronic ITP in adults. We report final data from a large prospective study of romiplostim in adults with ITP of varying duration and severity. Methods: Eligibility criteria were broad: patients ≥18 years of age, who had received prior ITP therapies (final protocol amendment: ≥1, previous amendments: ≥3), with low platelet counts (final amendment: ≤ 30 × 109/L, previous amendments: ≤ 10, ≤ 20 × 109/L) or experiencing uncontrolled bleeding. The only excluded comorbidities were: hematological malignancy, myeloproliferative neoplasms, MDS and bone marrow stem cell disorder. Romiplostim was initiated at 1 (final amendment) or 3 (previous amendments) μg/kg/week, with dose adjustments allowed to maintain platelet counts ≥50 × 109/L. Patients could continue on study until they had access to commercially available romiplostim. Rescue medications were allowed at any time; concurrent ITP therapies could be reduced when platelet counts were > 50 × 109/L. Primary endpoint was incidence of adverse events (AEs) and antibody formation. Secondary endpoint was platelet response, defined as either (1) doubling of baseline count and ≥ 50 × 109/L or (2) ≥20 × 109/L increase from baseline. Results: A total of 407 patients received romiplostim, 60% of whom were female. Median (Q1, Q3) time since ITP diagnosis was 4.25 (1.20, 11.40) years (maximum 57.1 years), with 51% of patients splenectomised and 39% receiving baseline concurrent ITP therapies. Seventy-one percent of patients completed the study, with requirement for alternative therapy and withdrawn consent the most common reasons for discontinuation (5% each). Median (Q1, Q3) on-study treatment duration was 44.29 (20.43, 65.86) weeks (maximum 201 weeks), with a total of 20,201 subject-weeks on study. Incidence and type of AEs were consistent with previous studies. The most common serious treatment-related AEs were cerebrovascular accident, headache, bone marrow reticulin fibrosis (with no evidence of positive trichrome staining for collagen and no evidence suggesting primary idiopathic myelofibrosis), nausea, deep vein thrombosis, hemorrhage and pulmonary embolism, with each reported in 2 of 407 (0.5%) patients. All other serious treatment-related AEs were each reported in one patient. Eighteen patients died; 3 deaths (hemolysis, intestinal ischaema, aplastic anemia) were considered treatment-related. No neutralizing antibodies to romiplostim or TPO were reported. Approximately 90% of patients achieved each of the platelet response definitions, regardless of splenectomy status. Overall, median (Q1, Q3) time to response was 2 (1, 4) weeks for response definition 1, and 1 (1, 3) week for response definition 2. Median (Q1, Q3) baseline platelet count was 14 (8, 21) × 109/L. After 1 week of treatment median (Q1, Q3) platelet count had increased to 42 (18, 101) × 109/L. From week 8 onwards, and excluding counts within 8 weeks of rescue medication use, median platelet counts were consistently above 100 × 109/L (range 101.0–269.5 × 109/L). Median (Q1, Q3) average weekly romiplostim dose was 3.62 (1.99, 6.08) μg/kg. Summary/conclusions: This is the largest prospective study in adult ITP reported to date. The data reported here are similar to those reported for previous romiplostim studies, with romiplostim able to safely induce a rapid platelet response in adult ITP patients with low platelet counts or bleeding symptoms. Romiplostim is an important, well-tolerated, treatment option for adult ITP patients, which significantly increases and maintains platelet counts. Adverse Event Subject Incidence Platelet Response Disclosures: Janssens: Amgen: Consultancy; Roche: Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees. Tarantino:Cangene corporation: Research Funding; Baxter: Research Funding; Talecris: Honoraria, Speakers Bureau; Up-to-date: Patents & Royalties; The Bleeding and Clotting Disorders Institute: Board Member. Bird:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees. Boccia:Amgen: Equity Ownership, Honoraria, Speakers Bureau. Lopez-Fernandez:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kozak:Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Steurer:Amgen: Honoraria. Dillingham:Amgen Limited: Employment, Equity Ownership. Lizambri:Amgen: Employment, Equity Ownership.

Association Of Platelet Function Markers, Independent Of Platelet Count, With Bleeding Score In Patients With Immune Thrombocytopenia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3534-3534
Author(s):  
Andrew L. Frelinger ◽  
Anja J Gerrits ◽  
Michelle A. Berny-Lang ◽  
Travis Brown ◽  
Sabrina L. Carmichael ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Platelet Function ◽  
Research Funding ◽  
Immune Thrombocytopenia ◽  
Univariate Analysis ◽  
Blood Draw ◽  
Platelet Surface ◽  
Platelet Counts ◽  
Bleeding Score

Abstract Background Immune thrombocytopenia (ITP) patients with similarly low platelet counts differ in their tendency to bleed. Aim To determine if differences in platelet function in ITP patients with similarly low platelet counts partly account for the variation in bleeding tendency. Methods The relationship between bleeding scores and platelet function markers was investigated in a single center cross-sectional study of pediatric patients with ITP. Following informed consent, blood was collected from ITP patients and bleeding was graded using the Buchanan and Adix Score (J Pediatr 2002) at routine clinic visits or while admitted to the hospital. Bleeding scores were obtained by one of three hematologists blinded to platelet function results, and investigators performing platelet function tests were blinded to clinical results. Platelet function was assessed by whole blood flow cytometric measurement of unstimulated, ADP- or TRAP-stimulated platelet surface activated GPIIb-IIIa (as measured by PAC1 binding), P-selectin, and GPIb and by unstimulated, convulxin-, or ADP plus TRAP-stimulated platelet surface phosphatidylserine expression (as determined by annexin V binding). Platelet count, immature platelet fraction (IPF) and mean platelet volume (MPV) were determined by a Sysmex XE-2100, and platelet forward angle light scatter (FSC) was measured by flow cytometry. Results Platelet function and bleeding scores were evaluated in 34 consecutive consenting pediatric ITP patients (16 female, 18 male, age 9.7 ± 5.7 years [mean ± SD]). ITP was newly diagnosed (< 3 months) in 10 patients, persistent (3 -- 12 months) in 7 patients, and chronic (>12 months) in 17 patients. Platelet count at the time of the blood draw was 47 ± 55 x 109/L. The median bleeding score on day of blood draw was 1 (range 0 to 4). By univariate analysis, higher IPF, and lower platelet count were significantly associated with a higher bleeding score (odds ratio [OR] >1, p<0.05) but MPV was not. Multiple measures of platelet function were associated with bleeding scores by univariate analysis: higher levels of platelet FSC (a measure affected by multiple variables including size) surface GPIb on unstimulated, ADP- or TRAP-stimulated platelets, surface P-selectin on unstimulated platelets, and platelet FSC were associated with increased odds for higher bleeding scores (ORs each >1, p<0.05), while higher ADP- and TRAP-stimulated platelet surface activated GPIIb-IIIa and P-selectin were associated with reduced odds of higher bleeding scores (ORs each <1, p<0.05). After adjustment for platelet count, higher levels of platelet surface P-selectin on unstimulated platelets, GPIb on TRAP-stimulated platelets, and FSC remained significantly associated with increased odds for higher bleeding scores (Figure), but IPF did not. Similarly, after adjustment for platelet count, higher TRAP-stimulated percentage of P-selectin and activated GPIIb-IIIa positive platelets remained significantly associated with reduced odds of higher bleeding scores (Figure). These findings were independent of recent ITP-related treatment. Conclusions In this study of pediatric ITP patients, we identified selected platelet function markers which, independent of platelet count, are associated with increased (platelet FSC, platelet surface P-selectin on unstimulated platelets, and GPIb on TRAP-stimulated platelets) or decreased (TRAP-stimulated percent P-selectin and GPIIb-IIIa positive platelets) odds of high bleeding scores. Possible hypotheses to explain these associations are as follows: 1) Increased P-selectin on unstimulated platelets demonstrates in vivo platelet activation, possibly as a consequence of the recent bleeding. 2) Because platelet activation results in a reduction in platelet surface GPIb and increases in platelet surface activated GPIIb-IIIa and P-selectin, the ORs associated with all of these markers could be explained by reduced ability of platelets in patients with higher bleeding scores to respond to agonists. 3) While platelet FSC is partly related to size, the finding that MPV and IPF, adjusted for platelet count, were not associated with bleeding score suggests that factors other than size account for the association of platelet FSC with higher bleeding scores. Further study is required to validate these findings and determine if differences in platelet function are associated with future risk for bleeding. Disclosures: Off Label Use: Eltrombopag was given to WAS/XLT patients for treatment of thrombocytopenia. Neufeld:Shire: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Apopharma: Consultancy. Michelson:Sysmex: Honoraria.

scholarly journals Safety and Efficacy of Romiplostim in over 200 Children with Immune Thrombocytopenia (ITP): Results of an Integrated Database of 5 Clinical Trials

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2428-2428 ◽  
Author(s):  
Michael D. Tarantino ◽  
Jenny M. Despotovic ◽  
John Roy ◽  
John Grainger ◽  
Nichola Cooper ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Platelet Response ◽  
Open Label ◽  
Advisory Committees ◽  
Baseline Platelet Count ◽  
Platelet Counts

Abstract Background: Romiplostim is approved globally for use in adults with ITP and in the EU for children with ITP. More comprehensive data are needed on the use of romiplostim in children with ITP. Objective: To examine the safety and efficacy of romiplostim in trials in children with ITP. Methods: Data were combined from 5 romiplostim trials in children with ITP, both placebo-controlled (a phase 1/2 and a phase 3 trial) and open-label (a 3-year trial and 2 extension trials); trial data have been reported previously (Bussel Blood 2011, Bussel PBC 2014, Tarantino Lancet 2016, Tarantino ASH 2017, Grainger ASH 2017). Platelet counts in the 4 weeks after use of rescue medication were excluded from analyses. Descriptive statistics were used. Number (n), mean, standard deviation (SD), median, quartile range (Q1, Q3), minimum (min), and maximum (max) for continuous variables, and number and percentage for categorical variables were provided. Results: Patients (N=286, 24 initially placebo and 262 initially romiplostim) had median (Q1, Q3) age of 10 (6, 13) years, ITP duration of 1.9 (1, 4) years, and baseline platelet count of 14 (8, 23)×109/L. Previously, 88% had received corticosteroids, 87% IVIg, and 21% rituximab; 23% had received >3 prior treatments and 7% had prior splenectomy. Of the 282 patients exposed to romiplostim (20 initially received placebo), the median (min, max) duration of treatment was 65 (8, 471) weeks, with a median (min, max) average weekly dose of 6.6 (0.1, 9.7) μg/kg; total exposure was 468 patient-years. The most common reasons for discontinuing the parent study for romiplostim-treated patients were per protocol (19%; eg, sponsor decision, death, lost to follow-up), consent withdrawn (3%), noncompliance (1%), and administrative decision (1%). Of romiplostim-treated patients, 24% had serious adverse events (SAEs), most commonly epistaxis, low platelet counts, and headache (Table). There were 7 cases of postbaseline neutralizing antibody against romiplostim: 2 transient and 5 persistent. There were no neutralizing antibodies against endogenous TPO. For patients undergoing bone marrow biopsies in the 3-year open-label trial, there were no findings of collagen or bone marrow abnormalities (Year 1 n=27, Year 2 n=5, vs. baseline) (Grainger et al, ASH 2017). One patient had an increase in modified Bauermeister bone marrow grade from 0 to 2 (fine reticulin fiber network) with no associated AEs (the only AEs were a cold and injection site pain); per protocol, there was no follow-up biopsy. Once at a steady dose of 10 μg/kg, most (11/16) of this patient's platelet counts were ≥30×109/L. Investigators reported thrombocytosis AEs; 1 patient had a platelet count of 1462×109/L at Week 14 for 1 week and another had elevated platelet counts 10 times between Weeks 20-172 (max of 872×109/L); there were no associated thrombotic events. Median platelet counts rose quickly and were over 50×109/L from Week 12 on (Figure). Platelet response rates also rose quickly. Overall, 89% of romiplostim-treated patients (vs 8% of placebo) had a platelet response (platelet counts ≥50×109/L; Figure). For romiplostim-treated patients, the first platelet responses occurred after a median of 6 weeks. The median % (Q1, Q3) of months responding was 76% (25%, 93%) and # of months responding was 11 (3, 20); from time of first monthly response, the median (Q1, Q3) % of months responding was 92% (75%, 100%) and # of months responding was 14 (7, 23). Nineteen romiplostim-treated patients discontinued all ITP therapies including romiplostim for ≥6 months while maintaining platelet counts ≥50×109/L (here defined as remission). These treatment-free periods lasted a median (Q1, Q3) of 12 (8, 14) months; no placebo patients remained free of treatment. There were no clear differences between those who did and did not enter remission (ie, age, sex, race, past treatment, ITP duration, baseline platelet count). Bleeding was reported for most (68%) patients: mostly grade 1/2, with 10% having grade 3 bleeding (most commonly epistaxis in 13 patients) and 2 patients having grade 4 bleeding (both reported as "ITP"). Conclusions: In this comprehensive database of romiplostim ITP trials in 286 children with 468 patient-years of romiplostim exposure, romiplostim was well tolerated. With romiplostim, the vast majority (89%) of patients had a platelet response, with some children able to discontinue all ITP treatments for ≥6 months. Disclosures Tarantino: Health Resources and Services Administration: Research Funding; Centers for Disease Control and Prevention: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Other: Reviews grants; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Grifols: Research Funding, Speakers Bureau. Despotovic:AmGen: Research Funding; Sanofi: Consultancy; Novartis: Research Funding. Grainger:Biotest: Consultancy; Ono Pharmaceuticals: Consultancy; Amgen: Consultancy, Honoraria, Other: Educational grant; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cooper:Amgen, Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Kim:Amgen Inc.: Employment, Equity Ownership. Eisen:Amgen Inc.: Employment, Equity Ownership.

Successful Discontinuation of Eltrombopag Treatment in Patients with Chronic ITP

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1085-1085 ◽  
Author(s):  
Emily Leven ◽  
Allison Miller ◽  
Nayla Boulad ◽  
Anis Haider ◽  
James B Bussel
Keyword(s):  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Rescue Therapy ◽  
Primary Response ◽  
Additional Treatment ◽  
Advisory Committees ◽  
Platelet Counts ◽  
Rescue Treatment ◽  
Immature Platelet Fraction

Abstract Abstract 1085 Introduction: Patients with immune thrombocytopenia (ITP) commonly experience platelet increases while under treatment with thrombopoietin-receptor agonists (TPO-RA). Anecdotal evidence suggests certain patients have been able to discontinue TPO-RA and still maintain platelet counts above baseline without additional treatment. This prospective ongoing study was designed to investigate the frequency and characteristics of patients exhibiting sustained responses after electively discontinuing eltrombopag (a TPO-RA) without substituting additional therapy. Methods: Enrolled patients were required to have ITP defined by consensus guidelines (Provan, Blood, 2009) for at least 6 months and must have been taking eltrombopag for a minimum of 4 months prior to starting this observational study. Rescue therapy is permitted once in the first 4 weeks off eltrombopag. The primary response endpoint was prospectively defined as a platelet count of ≥30,000/μl and ≥20,000/μl above initial baseline for 6 months off eltrombopag without intervening treatment (other than rescue). The secondary endpoint was being stably off therapy at 4 weeks after discontinuing eltrombopag. All patients who meet the 2 inclusion criteria (ITP for 6 months and eltrombopag for 4 months) are eligible for the study. Results: Fifteen patients are currently enrolled. Ages range from 3 to 86 years, median 55 years, with 10 females. There are 5 responders of 5 months or more (3 females, 2 males) and 10 non-responders (7 females, 3 males). Four of 5 responders have been off therapy for 6 months or more; the fifth “responder” has been off therapy for 5 months, with platelet counts ≥195,000/μL (figure 1). Responders are aged 19–86 years and have had ITP for 5–34 years; all had been on eltrombopag for > 2 years. Two responders were splenectomized and all had 3 or more prior therapies. One responder and 9 non-responders received rescue treatment in the first 4 weeks. One patient was a responder at 4 weeks, but she lost her response before reaching 6 months off-treatment. Factors not significantly associated with response were: age, duration of ITP, duration of eltrombopag therapy, splenectomy status, number of prior ITP treatments, bleeding history, and platelet count at the time that eltrombopag was discontinued. However, a lower absolute immature platelet fraction (AIPF) value at cessation of eltrombopag was seen in responders (fig 2, p=0.022). AIPF data for 1 non-responder is not available. An AIPF of 900 × 10/μl at the time of discontinuation of eltrombopag exceeds the AIPF of all 5 responders, but also of 3 of 9 non-responders. Conclusions: A substantial fraction of patients with ITP treated with eltrombopag, approximately 1/3, appear able to discontinue eltrombopag treatment and nonetheless maintain an at least adequate platelet count indefinitely (at the very least 6 months). Similar preliminary data has been reported with romiplostim (EHA and ASH abstracts). AIPF values (platelet retics) may better predict a patient's likelihood of successfully stopping therapy than other variables such as those listed above. Disclosures: Bussel: Amgen: Family owns Amgen stock Other, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; GlaxoSmithKline: Family owns GSK stock, Family owns GSK stock Other, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genzyme: Research Funding; IgG of America: Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai: Membership on an entity's Board of Directors or advisory committees, Research Funding; Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sysmex: Research Funding; Portola: Consultancy. Off Label Use: The use of romiplostim in pediatric patients was examined in this study.

An Interim Analysis Of a Phase 2, Single-Arm Study Of Platelet Responses and Remission Rates In Patients With Immune Thrombocytopenia (ITP) Receiving Romiplostim

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1074-1074 ◽  
Author(s):  
Roberto Stasi ◽  
Adrian Newland ◽  
Bertrand Godeau ◽  
Victor Priego ◽  
Jean-Francois Viallard ◽  
...  
Keyword(s):  
Platelet Count ◽  
Adverse Events ◽  
Board Of Directors ◽  
Treatment Period ◽  
Research Funding ◽  
Alternative Therapy ◽  
Platelet Response ◽  
Advisory Committees ◽  
Serious Adverse Events ◽  
Platelet Counts

Abstract Background We describe here platelet response and remission observed with romiplostim treatment in patients with ITP. Methods Patients with an ITP diagnosis for less than 6 months who received first-line therapies only (ie, corticosteroids, IVIG, anti-D) received QW romiplostim for up to 12 months in the treatment period (Fig 1). The primary objective was to describe the number of months with a platelet response during the 12-month treatment period; secondary objectives included incidence of ITP remission and splenectomy. The romiplostim dose was increased QW by 1 μg/kg from 1 μg/kg up to 10 μg/kg to reach a platelet count of ≥50x109/L, adjusting to maintain a platelet count of 50-200x109/L. Patients who maintained platelet counts ≥50x109/L on romiplostim only entered a dose-tapering period in which the romiplostim dose was decreased by 1 μg/kg Q2W as long as platelet counts remained ≥50x109/L. Starting when the dose tapered to 0 during either the 12-month treatment period or at the end of the dose-tapering period, patients were followed to determine whether they had ITP remission (24 weeks platelet counts ≥50x109/L without any treatment for ITP, including romiplostim). At the end of 12 months, patients who 1) had platelet counts ≤20x109/L for <4 consecutive weeks, 2) had platelet counts of 20-50x109/L, and/or 3) were receiving treatment for ITP besides romiplostim had the option to enter a stabilization period (≤8 weeks) while the investigator determined suitable post-study therapy. Patients with platelet counts ≤20x109/L for ≥4 consecutive weeks on the highest romiplostim dose were discontinued from the study for non-response. Interim data up to March 2013 are reported here. Results Of the patient population (N = 71), 59.2% were women, median (Q1, Q3) age was 37 (28, 56) years, median (Q1, Q3) time since ITP diagnosis was 2.2 (0.9, 4.4) months, and median (Q1, Q3) platelet count at screening was 20 (12, 25) x109/L. Past treatments included steroids (96%), IVIG (42%), and anti-D (1%). Prior to the study, platelet transfusions were received by 9% of patients. 30 patients (42%) completed treatment, 31 (44%) are continuing treatment, and 10 (14%) discontinued romiplostim (due to consent withdrawn n = 2, adverse event n = 3, requirement for alternative therapy n = 3, lost to follow-up n = 1, death n = 1). Patients had a median (Q1, Q3) of 51 (34, 52) weeks of treatment with a median (Q1, Q3) average QW dose of 2.1 (1, 3.8) μg/kg. 66 (93%) patients had a peak platelet count ≥50x109/L. The median (Q1, Q3) time with a platelet response was 9 (6, 12) months; the median (95% CI) time to platelet response was 2.1 (1.1, 3.1) weeks; platelet counts are in Fig 2. Of 38 evaluable patients (ie, known remission status), 11 (29%, 95% CI 15% to 46%) had ITP remission. One patient had a splenectomy and 6 had treatment failure (defined as platelet count ≤20x109/L for 4 consecutive weeks at 10 μg/kg QW, requirement of alternative therapy, or death). Of the 71 patients receiving romiplostim, 9 patients had serious adverse events (2 treatment-related: 1 case each of gastritis and increased transaminases). There were also 3 adverse events leading to discontinuation of romiplostim (non-Hodgkin's lymphoma, leukocytosis, and the aforementioned increased transaminases, these last 2 treatment-related). Other serious adverse events, also occurring in 1 patient each, included atrial fibrillation, dapsone syndrome, fecaloma, the aforementioned non-Hodgkin's lymphoma, pleuritic pain, and tendon rupture. There were no fatalities reported as adverse events; the death leading to discontinuation was due to cerebral hemorrhage which began before the patient received romiplostim. The most common adverse events were headache (17%), arthralgia (13%), and nasopharyngitis (10%). The most common hemorrhage adverse events were hematoma (7%), petechiae (7%), and epistaxis (7%). No bone marrow findings were reported. Conclusions In this trial, patients with an ITP diagnosis for less than 6 months treated with romiplostim had a high response rate (over 90%), with platelet responses occurring quickly (median time to response of 2 weeks) and median number of months with a platelet response of 9 months. To date, 29% of evaluable patients have shown remission (24 weeks of platelet counts ≥50x109/L without any ITP treatment). There were no new safety signals. Updated data from this ongoing study will be presented in the future. Disclosures: Stasi: Amgen: Honoraria, Speakers Bureau; GSK: Honoraria, Speakers Bureau; Genzyme: Honoraria, Speakers Bureau; Suppremol: Consultancy. Newland:Geron: Consultancy; Amgen: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; GSK: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Octapharma: Research Funding. Godeau:Amgen: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Roche: Consultancy, Research Funding; GSK: Consultancy; LFB: Consultancy. Jia:Amgen: Employment, Equity Ownership. Lopez:Amgen: Employment, Equity Ownership.

scholarly journals Improvement of platelet counts in steroid-unresponsive idiopathic immune thrombocytopenic purpura after short-course therapy with recombinant alpha 2b interferon [see comments]

Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 1894-1897 ◽  
Author(s):  
SJ Proctor ◽  
G Jackson ◽  
P Carey ◽  
A Stark ◽  
R Finney ◽  
...  
Keyword(s):  
Platelet Count ◽  
Partial Response ◽  
Immune Thrombocytopenia ◽  
Initial Response ◽  
Complete Responder ◽  
Thrombocytopenic Purpura ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Short Course ◽  
Steroid Refractory

Abstract In 13 patients with severe steroid-refractory idiopathic immune thrombocytopenia (ITP), a short course of recombinant alpha 2b interferon (IFN), given at a dose of 3 MU for 12 doses, caused a significant increase in platelet count in 11 patients. The rise in platelet count occurred following completion of the short course of IFN in 10 patients and occurred during therapy in one patient. Three patients showed an increase to normal platelet counts within 14 days of discontinuing the drug, eight showed a partial response, with a platelet count increase from 30 to 100 x 10(9)/L, and two patients showed minimal response. One complete responder relapsed at 5 months from initial response, and a further course of alpha 2b IFN caused a second prompt response with a rise of platelet count to supranormal levels. Short-course alpha 2b IFN can be recommended as a therapy for severe ITP. Responses are seen in splenectomized and nonsplenectomized subjects, and thrombocytopenia is not exacerbated during treatment.

scholarly journals Effects of Anti-Glycoprotein Antibodies on Response of Immune Thrombocytopenia Patients to Thrombopoietin Receptor Agonists and on Megakaryocytes Viability

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1048-1048
Author(s):  
Marina Izak Karaev ◽  
Alexandra Kruse ◽  
Margaret Morrisey ◽  
Heyu Ni ◽  
Zhu Guangheng ◽  
...  
Keyword(s):  
Platelet Count ◽  
Board Of Directors ◽  
Treatment Option ◽  
Research Funding ◽  
Immune Thrombocytopenia ◽  
Advisory Committees ◽  
Thrombopoietin Receptor Agonists ◽  
Platelet Counts ◽  
Thrombopoietin Receptor ◽  
Equity Ownership

Abstract Background Immune Thrombocytopenia (ITP) is a bleeding disorder due to a combination of increased platelet destruction and reduced production, often secondary to anti-platelet/megakaryocyte antibodies. The presence of antibodies to glycoproteins (GP) IIb/IIIa (integrin αIIbβ3) and GPIb/IX, detected in majority of ITP patients, may correspond to different responses to treatment, i.e., anti-GPIb is associated with more severe disease, and less responsive to intravenous immunoglobulins and steroids. Thrombopoietin Receptor Agonists (TPO-RA) increase platelet production by stimulation of megakaryopoesis. Predictors of response to TPO-RA and influence of antibody profile on response are currently unknown. In our previous study we investigated Absolute Immature Platelet Fraction (A-IPF) prior to TPO-RA treatment and did not find a correlation between A-IPF, anti-GP antibodies, and platelet counts. The aims of this study were to further investigate: 1. The role of anti-GP antibodies in response to TPO-RA; 2. Effect of patients' antibodies on megakaryocyte (MK) viability, maturation, apoptosis and formation of proplatelets (in vitro); 3. The influence of patients' clinical characteristics on response to TPO-RA. Materials and Methods 91 patients with persistent or chronic ITP, were treated at Weill Medical College of Cornell University until January 2015 with TPO-RAs: 52 patients received eltrombopag, 22 romiplostim and 17 avatrombopag. Serum samples of 84 patients were analyzed for the presence of anti-GP by MAIPA assay as previously described. Patients with baseline platelet counts less than <30x109/L were defined as responders to TPO-RA if the average of their six median monthly platelet counts was ≥50x109/L and doubled from average baseline counts (prior to TPO-RA). Patients with baseline platelet counts 30-50x109/L were responders if the average platelet count was ≥75x109/L. MKs were derived from human umbilical cord blood stem cells as previously described. Cells were grown using SFEM medium, adding on day 0 of culture 50 ng/ml recombinant TPO and aliquots of serum of ITP patients or healthy controls. The percentages of immature (CD41+/CD42-), mature (CD41+/CD42+), viable and apoptotic MKs were analyzed by flow cytometry on day 12. Apoptosis was analyzed by measuring Mitochondrial Outer Membane Potential (MOMP) and Phosphatidyl Serine (PS) externalization. MKs were considered apoptotic if they had positive staining for PS externalization, viable if positive for MOMP, and dead if positive for 7-Aminoactinomycin D (7AAD). Proplatelet formation by MKs was analyzed by microscopy. Statistical analysis using unpaired T-test and Pearson correlation test were performed. Results Ninety-one patients were included, 40 male (44%) and 51 female (56%), with a median age of 37.4 years (range 2-87). Median duration of ITP before TPO-RA treatment was 8 years (range 0.3-45). The 18/91 (19.8%) non-responders to TPO-RA were not different from the 73/91 responders in age, gender, number of prior treatments, duration of ITP, and past splenectomy. The presence of either or both anti-GP antibodies was correlated with average lower platelet counts on TPO-RA: 82.3 x109/L versus 123x109/L in patients without detected antibodies ("neither") (p=0.003). However, the response to TPO-RA was not influenced by the type of antibody: in patients with anti-GPIb the average platelet count was 76.1x109/L, and with anti-GPIIb/IIIa 80.7x109/L (Figure 1). In culture, excess dead MKs were found in anti-GPIb group and antiGPIb&antiGPIIb/IIIa group compared to "neither" group (p=0.0013 and p=0.027 respectively) and comparing antiGPIb&antiGPIIb/IIIa to control (p=0.0025). We did not observe changes in the degree of MK apoptisis or in MK maturation in the presence of serum antibodies. In cultures treated with serum of patients having anti-GPIb, less proplatelets were detected comparing to control (p=0.044) or to "neither" (p=0.0039). We conclude that patients with anti-GP antibodies respond less to TPO-RA, however there is no difference in response to TPO-RA between patients having anti-GPIb and anti-GPIIb/IIIa, unlike responses to other treatment modalities (e.g., steroids or immunoglobulins). TPO-RA could be a preferable treatment option in ITP patients having anti-GPIb. Figure 1. Average 6-months platelet counts of TPO-RA-treated ITP patients divided into groups by presence of antibody/ies. Figure 1. Average 6-months platelet counts of TPO-RA-treated ITP patients divided into groups by presence of antibody/ies. Disclosures Off Label Use: Eltrombopag, romiplostim and avatrombopag are a thrombopoietin receptor agonist approved for the treatment of thrombocytopenia in adults with chronic ITP. In some preliminary studies these medicines found as safe and effective treatment option in children and adolescents. Bussel:amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; Novartis: Consultancy, Research Funding; Genzyme: Consultancy; BiologicTx: Research Funding; Ligand: Consultancy, Research Funding; Eisai: Consultancy, Research Funding; Shionogi: Consultancy, Research Funding; momenta: Consultancy; Protalex: Consultancy; Symphogen: Consultancy.

scholarly journals Real-World Experience with Fostamatinib in Patients with Immune Thrombocytopenia at an Academic Medical Center

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4912-4912 ◽  
Author(s):  
David Hughes ◽  
Frances Blevins ◽  
Bhavesh Shah ◽  
Shayna Sarosiek ◽  
Adam Lerner ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Medical Center ◽  
Rescue Therapy ◽  
Academic Medical Center ◽  
Baseline Platelet Count ◽  
Platelet Counts ◽  
Therapy Initiation ◽  
Academic Medical ◽  
Insufficient Response

Introduction Fostamatinib is a first in its class oral inhibitor of spleen tyrosine kinase (Syk) pathway for treatment of adults with immune thrombocytopenia (ITP) with insufficient response to previous treatment. Choice of treatment for relapsed ITP varies greatly according to clinician and patient preference. It is common for patients to switch between available thrombopoietin (TPO) agonists and now fostamatinib. Titration of these agents is often cumbersome and labor intensive; romiplostim in particular requires weekly visits with lab draws and consumes nurse, pharmacy and provider effort. Here we present real world experience with fostamatinib use in an academic medical center. Methods. We retrospectively identified four patients who were prescribed fostamatinib within the past nine months at Boston Medical Center Health System. All patients had a diagnosis of chronic ITP and were previously treated with corticosteroids, intravenous immunoglobulin (IVIG), and rituximab. With respect to previous TPO receptor use, two of four patients had received both eltrombopag and romiplostim. Patients were started on fostamatinib at a dose of 100 mg by mouth twice daily and titrated up to 150 mg by mouth twice daily if platelet counts were <50 10x9 /L after 4 weeks of therapy. All patients were seen by a pharmacist and provider for initiation of the drug and seen in clinic weekly for the first month on therapy to assess toxicity and efficacy. The duration of follow up for the patients is between 2 and 9 months on therapy. Results. Three of four patients initiated on fostamatinib had a baseline platelet count 100K or greater and the fourth patient had ITP refractory to multiple lines of therapy with a baseline platelet count of 7K at therapy initiation. Three patients sought alternative therapy given side effects from TPO agonists or inconvenience of romiplostim. Three patients had platelets counts >50K at 4 weeks and one patient had a platelet count <30K. Recent platelet counts of the two patients that have been on therapy for 7 and 8 months were 123K and 108K, respectively. The third patient that responded initially discontinued therapy due to lack of stable response. Both of the patients with stable responses were well controlled on previous therapy with romiplostim. One patient required rescue therapy with IVIG and romiplostim due to petechiae 15 days after therapy initiation but continued on therapy thereafter. Two patients that discontinued therapy had platelet counts of 10K and 88K upon discontinuation due to inadequate response and toxicity, respectively. One patient was romiplostim naïve and the other patient had not received romiplostim for four years prior. Two patients developed diarrhea that was managed with loperamide and one led to treatment discontinuation (in combination with insufficient response). One patient experienced hypertension that was managed accordingly. Conclusion. The ideal place in therapy for fostamatinib in ITP therapy is not yet clear. However, the availability as an oral option for patients with refractory disease is appealing. One of our patients required rescue therapy which should be considered when transitioning patients to fostamatinib from TPO agonists. Additionally, side effect management with anti-hypertensives and anti-diarrheal agents may be required to continue therapy. Effectiveness of romiplostim may predict responsiveness to fostamatinib, although additional data are needed. Table Disclosures Shah: Rigel Pharmaceutical: Consultancy, Speakers Bureau. Sarosiek:Acrotech: Research Funding. Sloan:Merck: Other: endpoint review commitee; Abbvie: Other: Endpoint Review Committee; Stemline: Consultancy.

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