Treatment Of Chronic Immune Thrombocytopenia Research Articles

Targeting B cells in severe thrombotic thrombocytopenic purpura–a road to cure?*

Targeting B cells in severe thrombotic thrombocytopenic purpura–a road to cure?*

Final Results of Open-Label Treatment with Eltrombopag During ENABLE 1: A Study of Eltrombopag As An Adjunct for Antiviral Treatment of Hepatitis C Virus Associated with Thrombocytopenia

Abstract▪2232▪This icon denotes a clinically relevant abstract Introduction:Thrombocytopenia (TCP) is a common complication of cirrhosis in patients with hepatitis C virus (HCV) infections (Louie et al 2011); the presence of TCP impairs the ability to initiate peginterferon alpha (PEG) therapy and necessitates PEG dose reduction or discontinuation, thus reducing the potential for sustained virologic response (SVR). Eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist approved for the treatment of chronic immune thrombocytopenia, increases platelet counts in patients with TCP due to HCV-related cirrhosis (McHutchison et al 2007). ENABLE 1 was a phase 3, multicenter, two-part study of eltrombopag for the treatment of HCV-associated TCP. Part 1 involved open-label, pre-antiviral treatment with eltrombopag. Patients achieving platelet counts ≥90,000/μL were randomized in Part 2 to receive eltrombopag or placebo in combination with antiviral therapy (PEG-2a plus ribavirin). Aim: To assess the safety and efficacy of eltrombopag during the open-label, pre-antiviral treatment phase (Part 1) of ENABLE 1 in patients with cirrhosis. Methods: Patients with chronic HCV and a baseline platelet count <75,000/μL were enrolled. In Part 1, all patients received open-label oral eltrombopag (25 mg daily with dose escalations every 2 weeks to a maximum dose of 100 mg) for up to 9 weeks or until platelet counts reached ≥90,000/μL. Patients who failed to achieve platelet counts ≥90,000/μL following 3 weeks of eltrombopag 100 mg daily did not enter Part 2 and attended scheduled follow-up visits. Patients achieving these counts were randomized 2:1 to eltrombopag or placebo (Part 2) at the final dose received in Part 1, in combination with antiviral therapy for up to 48 weeks. Results: A total of 716 patients were enrolled; 1 patient withdrew due to a protocol deviation, and 715 entered the open-label pre-antiviral phase. At study entry, most patients were male (62%) and Caucasian (72%); 17% were of Japanese/East Asian heritage. The median age was 52 years (range, 19–76). 488 patients (68%) had cirrhosis (FibroSURE™ score equivalent to METAVIR F4). The median duration of treatment during Part 1 was 20 days and the median of the mean daily dose was 25 mg (range, 0.8–75 mg). Median baseline platelets were 59,000/μL; these increased to 89,000/μL by week 2 and remained consistently elevated throughout open-label treatment (Figure). Following a median of 2 weeks of treatment (range, 0.1–9.6 weeks), 691 patients (97%) achieved platelet counts ≥90,000/μL. Treatment was discontinued during Part 1 for 33 patients (5%): platelets <90,000/μL (11); adverse events (AEs, 9); investigator discretion (7); patient decision (3); loss of follow-up (2); or a protocol deviation (1). During Part 2, 682 patients (95%) were randomized, 2 patients withdrew consent following randomization, and 680 patients (95%) initiated antiviral treatment. Of the patients who initiated treatment, 451 (66%) did so within 2 weeks and 627 (92%) did so within 4 weeks. The most common AEs observed during the open-label treatment phase were headache (7%), fatigue (4%), nausea (3%), and diarrhea (3%). Ninety-five patients (13%) experienced platelet counts >200,000/μL. No thromboembolic events were observed during open-label treatment. Conclusions: Eltrombopag was generally well-tolerated and resulted in sustained increase in platelet counts during the open-label, pre-antiviral treatment phase. Platelet count increases were seen as early as 2 weeks following initiation of treatment. The vast majority of patients (97%) achieved platelet count increases to ≥90,000/μL, the threshold for initiating PEG-2a plus ribavirin therapy, and most did so within 4 weeks of initiating eltrombopag treatment. [Display omitted] Disclosures:Dusheiko:GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding. Off Label Use: Eltrombopag, inteferon and Ribavirin; eltrombopag is a thrombopoetin receptor agonist. Its efficacy and safety in raising platelet counts in hepatitis C positive patients (most with cirrhosis) and thrombocyotopaenia was studied in this protocol. Afdhal:Merck: Consultancy, Honoraria, Research Funding; Vertex: Consultancy, Honoraria, Research Funding; Idenix: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Springbank: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Pharmasett: Consultancy, Honoraria, Research Funding; Abbott: Consultancy, Honoraria, Research Funding. Giannini:GlaxoSmithKline: Consultancy, Speakers Bureau; Hoffman-LaRoche: Consultancy, Speakers Bureau. Chen:Bristol-Myers Squibb: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Mostafa Kamel:GlaxoSmithKline: Employment, Equity Ownership. Brainsky:GlaxoSmithKline: Employment, Equity Ownership. Geib:GlaxoSmithKline: Employment. Vasey:GlaxoSmithKline: Employment. Patwardhan:GlaxoSmithKline: Employment, company shares. Campbell:GlaxoSmithKline: Employment, Equity Ownership. Theodore:GlaxoSmithKline: Employment, Equity Ownership, Patents & Royalties.

Safety and Efficacy of Extended Treatment with Eltrombopag in Adults with Chronic Immune Thrombocytopenia (ITP) From June 2006 to February 2011,

Abstract 3296▪▪This icon denotes a clinically relevant abstract Background:Eltrombopag is an oral, nonpeptide thrombopoietin receptor agonist approved for treatment of chronic immune thrombocytopenia (ITP). In 6-week, and 6-month, placebo-controlled trials, eltrombopag safely increased platelets and reduced bleeding in patients (pts) with previously treated chronic ITP. EXTEND is an ongoing, open-label extension study of the safety and efficacy of long-term treatment with eltrombopag in chronic ITP pts. Methods: Pts had received eltrombopag or placebo in one of the following studies: TRA100773A or B (6-weeks), RAISE (6-months), or REPEAT (intermittent treatment). The EXTEND study was designed to: 1) identify an individual dose that increases platelets to ≥100,000/μL to support reduction of concomitant ITP medications, 2) identify a minimal dose of eltrombopag and concomitant ITP medication to maintain platelets ≥50,000/μL, and 3) evaluate long-term safety and efficacy. Pts completed the study if they completed ≥2 years of therapy and transitioned off study due to commercial availability of eltrombopag. Results: Of 301 pts enrolled, 21% (63) completed the study, 48% (143) withdrew, and 32% (95) remain on study. The most common reasons for withdrawal were adverse events (AEs, 14%), pt decision (13%), and lack of efficacy (11%). At baseline, platelet counts were ≤15,000/μL, >15,000-<30,000/μL, 30,000–50,000/μL, and >50,000/μL in 43%, 27%, 17%, and 13% of pts, respectively; 38% were splenectomized, 34% were receiving concomitant ITP medication, and 53% had received ≥3 previous ITP therapies. As of this report, 252, 215, 176, and 84 pts had been treated for ≥6 months, 1 year, 2 years, and 3 years, respectively. Twenty-three pts (8%) were treated for ≥4 years. Median duration of exposure was 121 weeks (range, 0.3–237 weeks). Overall, 88% (264/301) of pts achieved a platelet count ≥50,000/μL at least once. The proportion of pts achieving on-treatment platelets ≥50,000/μL was similar regardless of the following baseline characteristics: splenectomy vs no splenectomy (85% vs 89%); use vs no use of ITP medication (89% vs 87%); and platelet counts (<30,000/μL, 84%; 30,000–50,000/μL, 98%; >50,000/μL, 95%). Median platelet counts increased to ≥50,000/μL by week 2 and remained consistently ≥50,000/μL through week 208. The incidence of any bleeding symptoms (WHO grades 1–4) decreased from 56% at baseline to 16%, 19%, and 9% at weeks 52, 104, and 156, respectively. Clinically significant bleeding (WHO grades 2–4) decreased from 16% at baseline to 3%, 5%, and 0% at weeks 52, 104, and 156, respectively. AEs and serious AEs (SAEs) occurred in 89% (269) and 29% (86) of pts, respectively. The most frequent AEs were headache (27%), nasopharyngitis (24%), and upper respiratory tract infection (21%). Forty pts (13%) had AEs leading to withdrawal; 28 (9%) had SAEs leading to withdrawal. Twenty-five thromboembolic events (TEEs) have been reported in 19 pts (6%); the incidence rate is 3.02/100 pt years (95% CI [1.82–4.71]). Observed TEEs were deep vein thrombosis (10), central nervous system ischemic events (7), myocardial infarction (5), and pulmonary embolism (3). No association has been observed with elevated platelet counts, as only 3/19 pts experienced the TEE at or closest to their maximum platelet count achieved on study. Hepatobiliary laboratory abnormalities (HBLAs) meeting drug-induced liver injury screening criteria (Center for Drug Evaluation and Research 2009 [FDA]) were reported in 34 pts (11%). None were associated with signs of liver impairment, and most (n=30) resolved either while on treatment or after discontinuation. Eight pts were withdrawn as a result of their HBLA. Two pts were diagnosed with lymphoma and none with leukemia during the 622 pt years of eltrombopag exposure during EXTEND. An independent central review of bone marrow biopsies from >100 pts treated with eltrombopag for 1–4 years, including 39 pts who had ≥2 biopsies during the study, revealed no clinically significant increase in reticulin deposition. Conclusions: Eltrombopag was effective in increasing and maintaining platelet counts ≥50,000/μL and reducing bleeding symptoms. Eltrombopag was well-tolerated during treatment of pts with chronic ITP with exposures up to 4.5 years. No new safety signals have been observed in this long-term study. Additional long-term safety data continue to be assessed, especially in terms of bone marrow reticulin, HBLAs, and TEEs. Disclosures:Saleh:GlaxoSmithKline: Honoraria, Research Funding, Speakers Bureau. Cheng:GlaxoSmithKline: Speakers Bureau. Bussel:Portola: Consultancy; Eisai: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Cangene: Research Funding; Genzyme: Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sysmex: Research Funding. Burgess:GlaxoSmithKline: Employment, Equity Ownership. Marcello:GlaxoSmithKline: Employment. Bailey:GlaxoSmithKline: Employment, Equity Ownership. Brainsky:GlaxoSmithKline: Employment, Equity Ownership.

Rate of Cataracts Across the Eltrombopag Clinical Studies in Patients with Chronic Immune Thrombocytopenia

Abstract 1164▪▪This icon denotes a clinically relevant abstract Introduction:Systemic corticosteroids, a common first-line treatment for chronic immune thrombocytopenia (ITP), are known to be associated with an increased risk of cataracts. Feudjo-Tepie et al (2009) determined that the rate of cataracts was higher in patients treated with oral corticosteroids (14.0/1000 patient years [PYs] vs 6.0/1000 PY). Eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist, is approved for the treatment of chronic ITP, a disease characterized by low platelet counts. Preclinical studies of eltrombopag in young rodents showed the potential for cataract development at doses ≥4 times the human clinical exposure. The potential for an association between treatment with eltrombopag and an increased risk for cataracts was assessed in 5 clinical trials in chronic ITP. Methods: Ocular data from 5 trials were analyzed: 2 placebo-controlled, 6-week studies, TRA100773A (phase 2) and TRA100773B (phase 3); a 6-month, placebo-controlled phase 3 study (RAISE); a phase 2 study with 3 intermittent treatment cycles of up to 6 weeks (REPEAT); and an ongoing extension study (EXTEND, data from June 2006-February 2010). Ocular monitoring included assessment of ocular health history and cataract risk factors such as chronic corticosteroid use, and a complete ophthalmologic exam, including assessment of the lens using the Age-Related Eye Disease Study (AREDS) lens opacity grading protocol (AREDS Research Group, 2001). Ocular exams were performed at baseline, frequently during treatment, and 6 months following discontinuation of treatment. A Clinical Events Committee (CEC) composed of 3 external ophthalmologists was assembled to provide external medical review of the ocular data across the eltrombopag program. The CEC adjudicated the presence or absence of cataracts from treatment-blinded data and, where possible, made attributions of potential relatedness to study medication. Results: At baseline, 47/392 patients (12%) had pre-existing cataracts or were aphakic/pseudophakic. Across the trials, chronic corticosteroid use was the most commonly reported cataract risk factor, reported in 62% of patients with risk factor assessment. After CEC adjudication, in the two 6-week trials, 2/49 placebo-treated patients (4%) and 6/112 eltrombopag-treated patients (5%) had an incident cataract or progression of cataracts. All 8 patients reported prior use of corticosteroids, and 7/8 reported at least 1 risk factor for cataracts at their first ocular exam. In RAISE, 6/61 placebo-treated patients (10%) and 11/135 eltrombopag-treated patients (8%) had incident cataract or progression of cataracts. All 17 patients reported prior use of corticosteroids, identified as a risk factor at the baseline ocular exam. In REPEAT, the CEC identified 2/66 patients with potential cataract findings; given the additional risk factors in both patients, the CEC concluded there was no evidence of a drug-related increased risk of cataracts in the study. In the ongoing eltrombopag extension study, 25/299 patients (8%) had incident cataract or progression of cataracts. Twenty patients reported at least 1 cataract risk factor, and 24 patients had documented use of corticosteroids. The CEC noted variability in the AREDS lens grading, in which there was apparent progression followed by apparent regression to a lower, less severe grade on the AREDS scale. Conclusion: The CEC adjudication of the ocular data from the placebo-controlled eltrombopag studies in chronic ITP showed that a similar proportion of patients in the placebo- and eltrombopag-treatment groups had incident cataract or progression of cataracts. In the extension study, with patients exposed to eltrombopag for over 3 years, the proportion of patients with cataracts is similar to that observed in the placebo-controlled studies (despite the significant difference in exposure to eltrombopag). The noted variability in the AREDS lens grading reflects the inherent challenges for the clinician in implementing this scale in a consistent manner. Based upon the ocular data reviewed to date by the CEC, there is no evidence of an increased risk of cataract or cataract progression in chronic ITP patients treated with eltrombopag. The possibility of a relationship between eltrombopag and cataracts has not been completely excluded and is still being monitored in clinical trials. Disclosures:Cooper:GlaxoSmithKline: Honoraria. Wong:Biogen Idec: Honoraria, Research Funding; Sanofi: Research Funding; Bayer: Honoraria, Research Funding; GSK: Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau; Pfizer Inc: Research Funding; Roche: Research Funding; Leo Pharma: Honoraria; Johnson & Johnson: Research Funding. Brainsky:GlaxoSmithKline: Employment, Equity Ownership. Bailey:GlaxoSmithKline: Employment, Equity Ownership.

Romiplostim for the treatment of chronic immune thrombocytopenia in adult Japanese patients: a double-blind, randomized Phase III clinical trial

The efficacy and safety of romiplostim, a thrombopoietin-mimetic peptibody, were evaluated in a double-blind, placebo-controlled, randomized trial of Japanese patients with chronic immune thrombocytopenia (ITP). Thirty-four ITP patients received romiplostim (n=22) or placebo (n=12) for 12weeks, with a starting romiplostim dose of 3μg/kg weekly. The primary end point was the number of weeks with platelet response, defined as a platelet count ≥50×10(9)/L (not including the 4weeks after rescue medication administration). Patients received a median of 4 (range 1-19) prior ITP therapies including splenectomy in 44%. On study, 68% also received concomitant ITP therapy. Weekly responses occurred for a median of 11weeks with romiplostim as compared to 0weeks with placebo (p<0.0001). Most romiplostim-treated patients (95%) achieved platelet responses; two showed extended responses after the treatment period. The use of rescue medication was required in 9% of romiplostim-treated patients as compared with 17% of placebo-treated patients. Both treatment groups had similar incidences of adverse events (91% romiplostim, 92% placebo). Adverse events that occurred more frequently (>10%) in romiplostim-treated patients included nasopharyngitis, headache, peripheral edema, back pain, and extremity pain. In conclusion, romiplostim significantly increased and maintained platelet counts and was well tolerated in Japanese patients with ITP.

Eltrombopag for the treatment of chronic immune thrombocytopenia

Immune thrombocytopenic purpura (ITP) is an immune-mediated platelet disorder. Although early studies suggest that the main feature is antiplatelet antibody production and increased platelet clearance, more recent evidence implies that defective platelet production and suppressed maturation and differentiation of megakaryocytes also occurs. In this context, second-generation thrombopoietic agents, romiplostim and eltrombopag, have been developed for patients with chronic resistant/relapsing ITP. Eltrombopag has shown safety and efficacy in three double-blind randomized placebo-controlled multicenter studies. In these studies, a dose-dependent platelet increase to over 50 × 109/l was achieved in 58–60% of the patients. Bleeding episodes were significantly less in patients receiving eltrombopag relative to placebo. Platelet counts returned to baseline within 2 weeks of discontinuation of eltrombopag. Adverse events were mild and similar in eltrombopag- and placebo-treated groups. Transaminases increased, an...

EXTEND Study Update: Safety and Efficacy of Eltrombopag In Adults with Chronic Immune Thrombocytopenia (ITP) From June 2006 to February 2010

AbstractAbstract 67 Background:Eltrombopag is an oral thrombopoietin receptor agonist approved for treatment of chronic immune thrombocytopenia (ITP) in the US and other countries. In 6-week and 6-month placebo-controlled trials, eltrombopag safely increased platelet counts and reduced bleeding symptoms in patients with previously treated chronic ITP. The safety and efficacy of eltrombopag treatment are being evaluated in EXTEND, an ongoing open-label, extension study in ITP patients who completed a previous eltrombopag study. Methods:Enrolled patients had previously received eltrombopag or placebo in one of the following studies: two 6-week studies (773A and B), RAISE (6-month), or REPEAT (intermittent treatment). In EXTEND, specific goals include: 1) identification of a dose of eltrombopag that increases platelet counts (≥100,000/μ L) to support reduction of concomitant ITP medications (if taken); 2) identification of minimally effective doses of eltrombopag and concomitant ITP medication to maintain platelet counts ≥50,000/μ L; and 3) evaluation of the safety and efficacy of eltrombopag. Patients who completed at least 2 years of therapy and transitioned off study due to commercial availability of eltrombopag were considered to have completed the study. Results:Of 299 patients enrolled, 8% (23) completed the study, 41% (122) withdrew, and 52% (154) remain on study. The main reasons for withdrawal were adverse events (AEs, 11%), patient decision (11%), and lack of efficacy (10%). At baseline, platelet counts were ≤15, >15–<30, 30–50, and >50,000/μ L in 43%, 27%, 17%, and 13% of patients, respectively; 38% of patients were splenectomized; 33% were receiving concomitant ITP medication at baseline, and 53% had received ≥3 previous ITP therapies. 249, 210, 138, and 24 patients had been taking eltrombopag for ≥26, 52, 104, and 156 weeks, respectively, with a median duration of exposure of 100 weeks at the time of data analysis. The proportion of patients achieving a platelet count ≥50,000/μ L was similar regardless of the following baseline characteristics: splenectomy (84%) vs no splenectomy (89%); use of ITP medication (88%) vs no use of ITP medication (87%); and baseline platelet count <30,000/μ L (83%) vs 30–50,000/μ L (98%) vs >50,000/μ L (95%). Overall, 87% (261/299) of patients achieved a platelet count ≥50,000/μ L on treatment; 37 of these had a baseline platelet count of ≥50,000/μ L. Median platelet counts increased to ≥50,000/μ L by week 2 and remained consistently ≥50,000/μ L through week 164. The incidence of any bleeding symptoms (WHO grades 1–4) declined from 56% at baseline to 16% and 20% at weeks 52 and 104, respectively. Clinically significant bleeding (WHO grades 2–4) was reduced from 16% (47/299) at baseline to 3% (2/77) and 7% (3/41) at weeks 52 and 104, respectively. AEs and SAEs occurred in 88% (262) and 26% (79) of patients, respectively. The most frequent AEs were headache (26%), nasopharyngitis (23%), and upper respiratory tract infection (21%). AEs led to withdrawal of 13% (38) of patients, 9% (27) of which were due to SAEs.Twenty-one thromboembolic events (TEE) have been reported in 5% (16) of patients; the incidence rate is 3.17/100 patient years (95% CI [1.81, 5.15]). The most common TEEs were DVT (8) and MI (4). No association has been observed with elevated platelet counts, as only 3/16 patients experienced the TEE closest to their maximum platelet count achieved on study. Hepatobiliary laboratory abnormalities were reported in 29 patients (10%). All were reversible; the majority while on therapy. Of 299 patients enrolled, 6 (2%) have been withdrawn due to a hepatobiliary AE. After examining bone marrow biopsies from >150 patients treated with eltrombopag for >1 year, no clinically relevant increase in reticulin fiber deposition has been observed. Conclusions:Eltrombopag was effective in increasing and maintaining platelet counts ≥50,000/μ L and reducing bleeding symptoms. Eltrombopag has an overall positive risk/benefit assessment and was well tolerated during treatment of patients with chronic ITP even with exposures of more than 3 years. Bone marrow biopsies will continue to be assessed. Hepatobiliary laboratory abnormalities and thromboembolic events are risks that need to be monitored. Disclosures:Saleh:GlaxoSmithKline, Novartis, Imcoline, Celgene: Honoraria, Speakers Bureau. Cheng:GlaxoSmithKline: Consultancy, Honoraria, Speakers Bureau. Bussel:GlaxoSmithKline: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding. Mayer:GlaxoSmithKline: Employment, Equity Ownership. Bailey:GlaxoSmithKline: Employment. Brainsky:GlaxoSmithKline: Employment.

Romiplostim Treatment Mimicking Cyclic Thrombocytopenia In 3 Patients with Chronic Idiopatic Thrombocytopenic Purpura

AbstractAbstract 4665 IntroductionThe thrombopoietic growth factors (TGFs) are a novel class of compounds for the treatment of chronic immune thrombocytopenia (ITP). The first of these agents to receive regulatory approval, romiplostim and eltrombopag, have demonstrated impressive efficacy and tolerability in randomized controlled trials and open-label extension studies of several years duration and stand poised to revolutionize the management of ITP. Nonetheless, critical questions regarding the safety of these agents, remain partially unanswered. The aim of this report is to focus on the incidence of thrombocytosis and rebound thrombocytopenia mimicking cyclic thrombocytopenia in a series of 15 patients treated with romiplostim in a single institution. Methods15 patients (8 M and 7 F, median age 45 years range 21–76) with chronic ITP (median onset 6 years, range 1–11), 1/15 splenectomized, plts median 2 ×109/L, (range 18–24) were treated with Romiplostim initial dose of 1 mg/kg, weekly checks, with only weekly increase of 1 mg/kg to reach a platelet count ≥ 50 × 109/L. The target platelet count range was 50 to 250 × 109/L. Twenty-two percent of patients (3/15) were receiving concurrent treatment for ITP (corticosteroids, danazol) at the time of first romiplostim dose. These medications were discontinued after platelet counts reached 50 × 109/L. ResultsA platelet response had been achieved by 30% of patients after the first dose and by 51% of patients after the third dose. Treatment response was observed in 100% of pts treated after 6 weeks. In three patients after the eighth week, with average values plts 120×109/l, the subsequent administration of the drug led to an increase in platelet count > 1000×109/l, with rapid fall to <30 ×109/l at the third week suspension in 2/3, while the third patient is in CR at six months follow-up despite treatment was stopped. ConclusionAccording to an analysis of all patients with ITP treated with romiplostim in 4 controlled trials have been reported 3 thrombocytosis events in 271 pts (1.1%). In our series the percentage was 20% (3/15), much higher than that reported in the literature, with no thrombotic complications related. Interesting in a case CR was still maintained at 8 months of follow-up despite cessation of treatment. It would be very useful to create a network of information between users of romiplostim to evaluate on a larger series, the true incidence of thrombocytosis and any related thrombotic phenomena associated in a day by day clinical practice. Disclosures:No relevant conflicts of interest to declare.

Toxicities of the Thrombopoietic Growth Factors

The thrombopoietic growth factors (TGFs) are a novel class of compounds for the treatment of chronic immune thrombocytopenia (ITP). The first of these agents to receive regulatory approval, romiplostim and eltrombopag, have demonstrated impressive efficacy and tolerability in randomized controlled trials and open-label extension studies of several years duration and stand poised to revolutionize the management of ITP. Nonetheless, critical questions regarding the safety of these agents, particularly after long-term administration, remain partially unanswered. The objective of this review is to describe the reported and potential toxicities of the TGFs, including bone marrow fibrosis, thrombosis, rebound thrombocytopenia, hematologic malignancy, neutralizing antibody formation, hepatotoxicity, cataract formation, and common adverse events. The incidence and clinical implications of these toxicities as well as strategies for patient safety monitoring are examined.

Safety of the Thrombopoiesis-Stimulating Agents for the Treatment of Immune Thrombocytopenia

The thrombopoiesis-stimulating agents (TSAs) are a novel class of drugs for the treatment of chronic immune thrombocytopenia (ITP). Roimplostim and eltrombopag, the first two TSAs to enter clinical use, received regulatory approval in 2008 and stand poised to change the treatment paradigm in ITP. However, important questions regarding the safety of these agents, particularly with long-term use, remain partially unanswered. The primary objective of this article is to review the reported toxicities associated with the TSAs including rebound thrombocytopenia, thrombosis, hepatotoxicity, formation of neutralizing antibodies, bone marrow fibrosis, hematologic malignancy, cataract formation, and common adverse events. The incidence and severity of these toxicities as well as strategies for monitoring patient safety and pharmacovigilance are discussed.

Successful treatment of chronic immune thrombocytopenia using fresh frozen plasma.

Successful treatment of chronic immune thrombocytopenia using fresh frozen plasma.

The use of intravenous immunoglobulin (endobulin) in patients with immune thrombocytopenia.

Six adults were treated for chronic immune thrombocytopenia (ITP) with high dose intravenous immunoglobulin (ENDOBULIN). Five patients were evaluable. In four patients the platelet associated IgG (PAIgG) levels were increased. All four responded to i.v. Ig and two subsequently underwent splenectomy. One patient had normal PAIgG and had no response to i.v. Ig. Endobulin is useful in the treatment of chronic ITP and is followed in some patients by a prolonged response. High levels of PAIgG may predict a favourable outcome.

Treatment of Chronic Immune Thrombocytopenia

Treatment of Chronic Immune Thrombocytopenia