Sustained Complete Remission Of Corticosteroid-Resistant Immune Thrombocytopenia With a Short Course Of Recombinant Human Thrombopoietin

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4746-4746 ◽  
Author(s):  
Hai Zhou ◽  
Ping Qin ◽  
Jihua Qiu ◽  
Linlin Shao ◽  
Yawen Wang ◽  
...  
Keyword(s):  
Platelet Count ◽  
Complete Remission ◽  
Fold Increase ◽  
Complete Response ◽  
Baseline Platelet Count ◽  
Platelet Counts ◽  
Time To Peak ◽  
Short Course ◽  
Daily Dose ◽  
Recombinant Human Thrombopoietin

Thrombopoietin (TPO) and TPO receptor agonists have substantially broadened the therapeutic options for patients with immune thrombocytopenia (ITP). Platelet count response of ITP is usually maintained during the medication; however, once it is stopped, platelet counts commonly drop to pretreatment levels. We report three corticosteroid-resistant ITP patients achieving sustained complete remission with one short-term application of recombinant human thrombopoietin (rhTPO). Thirty-two adult ITP patients (18 females and 14 males; age range 18-72 years, median 45 years) were enrolled between December, 2011 and July, 2013 at the Department of Hematology, Qilu Hospital, Shandong University. Patients were diagnosed according to the recently published criteria (Rodeghiero F et al, Blood 2009). All patients had a baseline platelet count (PC) of < 30 x 109/L and bleeding symptoms, and were resistant to prior corticosteroid therapy or splenectomy. Recombinant human thrombopoietin (rhTPO, a truncated and non-glycosylated TPO developed by 3SBIO Pharmaceutical Co., LTD, Shenyang, China, approved by China State Food and Drug Administration) was given subcutaneously at a daily dose of 1.0 µg/kg for 14 days. Withdrawal of rhTPO could be performed while platelet count rose to above 100 x 109/L in less than 14 days. Responses were required to be independent of supportive medications. The criteria for response were defined as follows: (1) complete response (CR): platelet count > 100 x 109/L; (2) response (R): platelet count > 30 x 109/L and at least 2-fold increase of the baseline platelet count and absence of bleeding; (3) no response (NR): platelet count < 30 x 109/L or less than 2-fold increase of the baseline platelet count or bleeding. Of the 32 ITP patients treated with rhTPO, the complete response (CR), response (R), overall response (OR) and no response (NR) rates were 37.50% (12/32), 28.12% (9/32), 65.62% (21/32) and 34.38% (11/32), respectively. Among the 32 patients, three (9.38%) acquired sustained complete response (i.e., platelet count > 100 x 109/L and no clinical symptoms for at least six months after the medication). Of these three patients, the time to peak response was 28, 20 and 28 days, and the peak values of platelet counts were 215 x 109/L, 245 x 109/L and 296 x 109/L, respectively. These three patients’ information was shown in Table 1. Their platelet count responses sustained for 56, 40 and 28 weeks without any ITP-specific treatments after the cessation of rhTPO (Figure 1). In addition, only mild adverse events (WHO grades 1-2) were observed, including fever, fatigue and insomnia.Table 1Characteristics of the three ITP patients who achieved a durable complete response associated with the use of rhTPO.PatientAge(years)SexBaseline Platelet Count (x109/L)rhTPO Daily Dose(µg/kg)rhTPO Duration(days)Time to Peak Response(days)Peak Value of Platelet Count(x109/L)Complete Remission off rhTPO(Weeks)172Female21122821556234Female51102024540354Male81142829628Figure 1Serial platelet counts of three ITP patients who achieved a definite rhTPO-induced sustained remission.Figure 1. Serial platelet counts of three ITP patients who achieved a definite rhTPO-induced sustained remission. In conclusion, some ITP patients can achieve sustained complete remission after a short-course of rhTPO. However, the mechanism behind this is unclear. Disclosures: No relevant conflicts of interest to declare.

Recombinant Human Thrombopoietin (rh-TPO) in Combination with Rituximab As a Novel Therapy in Corticosteroid-Resistant Primary Immune Thrombocytopenia (ITP)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2223-2223
Author(s):  
Li Guo ◽  
Xiaoyuan Dong ◽  
Jie Li ◽  
Danyan Ji ◽  
Ping Qin ◽  
...  
Keyword(s):  
Platelet Count ◽  
Receptor Agonist ◽  
Response Rate ◽  
Fold Increase ◽  
Complete Response ◽  
Sustained Response ◽  
Novel Therapy ◽  
Baseline Platelet Count ◽  
Primary Immune Thrombocytopenia

Abstract Abstract 2223 Background: Both thrombopoietin (TPO) receptor agonist and rituximab were recommended as second-line options for adult primary immune thrombocytopenia (ITP) according to the 2010 International Consensus Guideline. The mechanism of rituximab therapy mainly refers to inhibition of accelerated platelet destruction mediated by autoantibody, while the latter, TPO receptor agonist, is reported to be effective in the salvage of impaired platelet production in patients. Despite the considerable response rate (about 50–70%) and sustained response (about 20–40%), the median time to response (TTR) was about 5.5 weeks for patients undergoing rituximab therapy, indicating high bleeding risk in the early stage of the treatment (Arnold, et al. Ann Intern Med. 2007;146:25–33.). On the other hand, novel TPO receptor agonists could initiate fast but unenduring responses. We hereby report a novel therapy which combines low-dose rituximab with short-term application of a TPO receptor agonist, the recombinant human thrombopoietin (rh-TPO), based on the preliminary results of an ongoing multi-centered, non-randomized clinical study in corticosteroid-resistant adult ITP patients. Patients: Twenty-one adult ITP patients were enrolled since December, 2009. All the subjects had a baseline platelet count (PC) of <30×109/L or bleeding, were refractory to, or had relapsed after, at least one prior corticosteroids therapy and splenectomy, or acquired corticosteroid-resistance but were excluded from splenectomy, without application of other second-line therapies recommended in the Guideline in the previous 3 weeks. Methods: Rituximab was given intravenously at a dose of 100 mg weekly for 4 consecutive weeks (Day 1, 8, 15, 22). Rh-TPO (TPIAO™, a product of Sunshine Pharmaceutical Co Ltd, China, approved by China State Food and Drug Administration) was given subcutaneously at a dose of 1.0 μg/kg daily for 14 days (Day 1–14). PC was monitored every three or four days until day 22, followed by tests every week. Responses were required to be independent of measures and supportive platelet transfusion. The criteria for response were defined as follows: (1) complete response (CR): platelet count >100×109/L and; (2) response (R): platelet count>30×109/L and at least 2-fold increase the baseline count and absence of bleeding; (3) No response (NR): platelet counts <30×109/L or less than 2-fold increase of baseline platelet count or bleeding. TTR: times from starting treatment to time of achievement of CR or R. Patients were followed for 3 months, and any adverse effects were recorded during the period of treatment and during the follow-up. Results: All the patients received the therapy, but 4 were lost during follow-up. The efficacy of treatment is outlined in Table 1. Compared with rituximab alone, the combination therapy resulted in a rapid response (TTR 9 vs. 21–44 days) with similar response rate (CR 57% vs. 30–60%, OR 76% vs. 50–70%). Moreover, the rh-TPO seemed to not only shorten the TTR but also significantly increase the sustained response (69% vs. 20–40%), indicating a synergistic effect with rituximab. In addition, there was no toxicity overlap observed. Adverse events recorded were mild (WHO grades 1–2), including fever (2), fatigue (2), myalgia (2), secondary infection (2), chills (1),and insomnia (1). No serious adverse events occurred during the course of treatment and the period of follow-up. Conclusions: The efficacy of this novel combination therapy are very satisfactory, considering the higher overall and complete response, shorter TTR as well as higher sustained response, in comparison with administrating rituximab alone. However, the combination should be used with caution and needs further and larger scale observation, especially to monitor for serious adverse effects such as thrombosis, bone marrow fibrosis and infection. Disclosures: No relevant conflicts of interest to declare.

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.

Multiple Cycles of Recombinant Human Thrombopoietin Therapy in a Patient with Chronic Refractory Idiopathic Thrombocytopenic Purpura.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3933-3933
Author(s):  
Yongqiang Zhao ◽  
Baolai Hua ◽  
Nong Zou ◽  
Shujie Wang ◽  
Tienan Zhu
Keyword(s):  
Platelet Count ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Immunosuppressive Agents ◽  
Plasma Concentrations ◽  
Thrombocytopenic Purpura ◽  
Platelet Production ◽  
Platelet Counts ◽  
Multiple Cycles ◽  
Recombinant Human Thrombopoietin ◽  
Refractory Itp

Abstract Thrombopoietin (TPO) is the key regulator of megakaryocytepoiesis and platelet production. TPO binds to its specific receptor, c-Mpl, on the surfaces of megakaryocytes, and may promote the proliferation, differentiation and maturation of megakaryocytes, and finally increase the circulating platelet count. The role of TPO in the pathogenesis of idiopathic thrombocytopenic purpura (ITP) is not certain. Plasma concentrations of TPO in ITP patients were similar to or little lower than that in healthy subjects. Therefore it is possible that supplemental TPO could significantly promote platelet production and increase platelet counts in ITP patients. Here, we report the result of multiple cycles of recombinant human thrombopoietin (rhTPO) therapy in a patient with refractory ITP. The patient, a 42-year-old woman, was admitted to our department on December 30, 2003. She had suffered from chronic ITP for more than 4 years. The patient had been treated with glucocorticosteroids, immunosuppressive agents and splenectomy. No sustained response could be achieved. The diagnosis of chronic refractory ITP was made. There were petechiae and gingival bleeding on admission. Liver and spleen were not palpable. Hemoglobin was 142g/L, white blood cell count 7.6×10 9/L, platelet count 15×10 9/L. Bone marrow aspiration revealed that erythroid and myeloid development were normal, megakaryocytes were increased in number and no dysplastic features. After an informed consent was obtained from the patient, rhTPO (Sunshine Pharmaceutical Corporation, China) was administrated subcutaneously at dosage of 1.0 μg/kg, daily for 14 days or until platelet count sustained more than 50×109/L. Anti-rhTPO antibodies were determined weekly by ELISA. Three cycles of rhTPO therapy was given with 6, 13 and 8 dosing for each cycle. The platelet counts before each cycle were all less than10×109/L and increased above 50×109/L on day 5, 11 and 8 of rhTPO administration, respectively. The peak platelet counts of 456, 130 and 82×109/L were reached on day 9, 15 and 13 for each cycle. Then platelet count decreased gradually. The durations of platelet count more than 50×109/L in 3 cycles were 13, 7 and 10 days respectively. No increase of WBC count and Hb level occurred. No liver and kidney function damage, abnormal coagulation functions or thrombosis developed during the treatment. rhTPO antibodies were not detectable. The result indicated that rhTPO could transiently increase peripheral platelet counts of the patient with chronic refractory ITP. It was uncertain why peak platelet counts declined and durations of platelet count more than 50×109/L shortened when multiple cycles of rhTPO were given.

Platelet Counts Following Eltrombopag Discontinuation in Patients with Chronic Immune Thrombocytopenic Purpura.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3517-3517
Author(s):  
Gregory Cheng ◽  
Michael Tarantino ◽  
Terry Gernsheimer ◽  
Oliver Meyer ◽  
Andres Brainsky ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenic Purpura ◽  
Research Funding ◽  
Rescue Medication ◽  
Study Medication ◽  
Bleeding Events ◽  
Thrombocytopenic Purpura ◽  
Baseline Platelet Count ◽  
Platelet Counts ◽  
Transient Decrease

Abstract Abstract 3517 Poster Board III-454 BACKGROUND Eltrombopag (PROMACTA®; GlaxoSmithKline, Collegeville, PA, USA) is an oral, small molecule (565 Da), thrombopoietin receptor agonist that has been approved in the United States for the treatment of patients with chronic immune thrombocytopenic purpura (ITP). It is also being studied in thrombocytopenic patients with chronic liver disease, hepatitis C, myelodysplastic syndromes, and cancer. Withdrawal of treatments that stimulate platelet production may theoretically result in recurrent thrombocytopenia below pretreatment levels (below baseline). OBJECTIVE: To determine whether worsening of thrombocytopenia (ie, platelet count decrease below baseline) occurs after discontinuation of eltrombopag in patients with chronic ITP. METHODS: The lowest median platelet counts during the first 4 weeks posttherapy were compared with median baseline platelet counts. Data from 369 patients treated in 3 randomized, double-blind, placebo-controlled studies were analyzed: TRA100773A and TRA100773B were 6-week studies, and RAISE was a 6-month study. For all 3 studies, a baseline platelet count <30,000/μL was required. Platelet counts, bleeding events, and the use of ITP medication were examined in the 4 weeks following the discontinuation of eltrombopag or placebo. A transient decrease in platelet counts (ie, worsening of thrombocytopenia) was defined as a platelet count below 10,000/μL and at least 10,000/μL below each patient's baseline platelet count (Bussel N Eng J Med 2006). RESULTS: Using pooled data from the 3 studies, no decreases below baseline median platelet counts (placebo, 16,300/μL; eltrombopag, 16,000/μL) were observed compared to the lowest median platelet counts within the first 4 weeks posttherapy (placebo, 14,000/μL; eltrombopag, 17,000/μL). Across the pooled studies, a total of 10/128 (8%) of placebo-treated patients and 20/241 (8%) of eltrombopag-treated patients had a transient decrease in platelet counts in the 4 weeks following discontinuation or interruption of treatment. None of the 10 placebo-treated patients had bleeding events associated with posttreatment platelet nadirs. Three of the 20 eltrombopag-treated patients had bleeding events and/or rescue treatment associated with the platelet nadir in the 4-week posttreatment period. One patient discontinued eltrombopag after achieving platelet counts >200,000/μL following on-therapy rescue medication (corticosteroid 0.5 mg/kg/day); 9 days after discontinuing study medication, the patient had grade 1 gum bleeding and resumed daily corticosteroids at an increased dose. The second patient had grade 3 menorrhagia and was administered vincristine (patient had a history of similar symptoms). The third patient had Henoch-Schoenlein purpura, interrupted eltrombopag due to platelet counts >400,000/μL, and 7 days after holding eltrombopag had a platelet count of 2000/μL, experienced grade 1 mouth hemorrhage and grade 2 petechiae, and did not require rescue medication. The patient continued in the study for the full 6 months and following permanent discontinuation of eltrombopag, this patient did not experience a transient decrease in platelet counts or any bleeding. CONCLUSION: Across 3 placebo-controlled studies, the incidence of transient decreases in platelet counts following discontinuation or interruption of study medication was similar in patients receiving eltrombopag or placebo. Therefore, these decreases may be unrelated to study medication and may represent normal fluctuations in platelet counts in patients with chronic ITP. Transient platelet count decreases were generally not associated with bleeding events. Disclosures: Cheng: GlaxoSmithKline: Research Funding. Tarantino:GlaxoSmithKline: Speakers Bureau; Lundbeck: Speakers Bureau; Baxter: Membership on an entity's Board of Directors or advisory committees. Gernsheimer:GlaxoSmithKline: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. Meyer:GlaxoSmithKline: Consultancy, Honoraria. Brainsky:GlaxoSmithKline: Employment. Stone:GlaxoSmithKline: Employment.

Platelet Doubling After the First Azacitidine Cycle Is a Promising Predictor for Response in MDS, CMML and AML Patients in the Dutch Azacitidine Compassionate Patient Named Program,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3841-3841
Author(s):  
Geert A Huls ◽  
Lieke H. van der Helm ◽  
Canan Alhan ◽  
P.W. Wijermans ◽  
Marinus van Marwijk Kooy ◽  
...  
Keyword(s):  
Platelet Count ◽  
High Risk ◽  
Fold Increase ◽  
Risk Groups ◽  
Low Risk ◽  
Logrank Test ◽  
Baseline Platelet Count ◽  
Routine Administration ◽  
Ortho Biotech ◽  
Chronic Myelomonocytic Leukaemia

Abstract Abstract 3841 The efficacy of azacitidine in the treatment of high risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20–30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors for response, we analyzed a cohort of 90 MDS, CMML and AML patients who have been treated in a Dutch compassionate patient named program. Patients received azacitidine for a median of 5 cycles (range 1–19). The overall response rate (CR/PR/HI) was 57% in low risk MDS, 53% in high risk MDS, 50% in CMML, and 39% in AML patients. Median overall survival (OS) was 13.0 (9.8–16.2) months. In multivariate analysis we confirmed that circulating blasts (HR 0.48, 95% CI 0.24–0.99; p=.05) and poor risk cytogenetics (HR 0.45, 95% CI 0.22–0.91; p=.03) are independent predictors for OS. Interestingly, in this analysis we also identified platelet doubling after the first cycle of azacitidine as a simple and independent positive predictor for OS (HR 5.4, 95% CI 0.73–39.9; p=.10). Of the 90 treated patients, 14 (16%) had an at least two-fold increase in platelet count after the first cycle of azacitidine, which was associated with significant better OS (p=.01, according to logrank test) (figure). Of these 14 patients 13 could be classified according the azacitidine prognostic scoring system for OS as recently proposed by Itzykson et al. (Blood:2011;117:403); 6 patients belonged to the low risk and 7 to the intermediate risk group. Median baseline platelet count of these patients was 35 x109/L (range 2–290 x109/L). Characteristics of this subgroup of patients were not significantly different from the patients without platelet doubling. Interestingly, platelet doubling was observed in all cytogenetic risk groups, in patients with and without circulating blasts, and in patients who are transfusion dependent and independent. In conclusion, routine administration of azacitidine to patients with variable risk groups of MDS, CMML and AML is feasible and subgroups with distinct efficacy of azacitidine treatment can be identified. Disclosures: Wijermans: Centocor Ortho Biotech Research & Development: Research Funding.

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.

scholarly journals Treatment of adult chronic autoimmune thrombocytopenic purpura with repeated high-dose intravenous immunoglobulin

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1415-1421 ◽  
Author(s):  
B Godeau ◽  
S Lesage ◽  
M Divine ◽  
V Wirquin ◽  
JP Farcet ◽  
...  
Keyword(s):  
Body Weight ◽  
Platelet Count ◽  
Treatment Protocol ◽  
Complete Response ◽  
Long Term Results ◽  
High Dose ◽  
Thrombocytopenic Purpura ◽  
Autoimmune Thrombocytopenic Purpura ◽  
Platelet Counts

Intravenous (i.v.) infusions of Ig concentrates are an effective but expensive treatment for patients with autoimmune thrombocytopenic purpura (AITP). The optimal treatment protocol and the long-term results are uncertain, and the precise mechanism by which the platelet count increases is poorly understood. Twenty adult patients with chronic AITP were enrolled in a prospective study to compare the respective efficacy of two high-dose IVIgG induction regimens (1 g v 2 g/kg body weight) and the long-term effect of six 1 g/kg body weight i.v. IgG reinfusions. An initial response was observed in all 18 evaluable patients: the platelet count increased to a mean value of 251 x 10(9)/L (range 72 to 836 x 10(9)/L) and the mean pretreatment platelet count was multiplied by 14.6. No difference in efficiency was observed between the two i.v. IgG dosages. The degree of the platelet count increment correlated in both groups with the increase in the clearance of antibody-coated red blood cells, measured by an isotopic method, but not with the serum IgG elevation. Treatment was considered to have failed in 11 patients, 90 days after the last i.v. IgG reinfusion (D90), because the platelet counts were comparable with pretreatment values. In contrast, a complete response was observed at D90 in five patients (mean platelet count: 184 x 10(9)/L; range: 150 to 250 x 10(9)/L) and a partial response at D90 was obtained in the remaining two patients (platelet counts: 70 and 104 x 10(9)/L). Five of the 7 responders at D90 kept a platelet count above 50 x 10(9)/L during the entire follow-up period (mean 33 months; range: 5 to 66) with no further treatment; unfortunately, no clinical or biologic criteria were found to be predictive of the long-term response. This study shows that an i.v. IgG infusion regimen of 1 g/kg body weight could safely replace the classical 2 g/kg body weight dosage, at least in patients who do not have life-threatening thrombocytopenia. Moreover, repeated i.v. IgG reinfusion could be an alternative for AITP patients in whom splenectomy is contraindicated.

scholarly journals Treatment of adult chronic autoimmune thrombocytopenic purpura with repeated high-dose intravenous immunoglobulin

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1415-1421 ◽  
Author(s):  
B Godeau ◽  
S Lesage ◽  
M Divine ◽  
V Wirquin ◽  
JP Farcet ◽  
...  
Keyword(s):  
Body Weight ◽  
Platelet Count ◽  
Treatment Protocol ◽  
Complete Response ◽  
Long Term Results ◽  
High Dose ◽  
Thrombocytopenic Purpura ◽  
Autoimmune Thrombocytopenic Purpura ◽  
Platelet Counts

Abstract Intravenous (i.v.) infusions of Ig concentrates are an effective but expensive treatment for patients with autoimmune thrombocytopenic purpura (AITP). The optimal treatment protocol and the long-term results are uncertain, and the precise mechanism by which the platelet count increases is poorly understood. Twenty adult patients with chronic AITP were enrolled in a prospective study to compare the respective efficacy of two high-dose IVIgG induction regimens (1 g v 2 g/kg body weight) and the long-term effect of six 1 g/kg body weight i.v. IgG reinfusions. An initial response was observed in all 18 evaluable patients: the platelet count increased to a mean value of 251 x 10(9)/L (range 72 to 836 x 10(9)/L) and the mean pretreatment platelet count was multiplied by 14.6. No difference in efficiency was observed between the two i.v. IgG dosages. The degree of the platelet count increment correlated in both groups with the increase in the clearance of antibody-coated red blood cells, measured by an isotopic method, but not with the serum IgG elevation. Treatment was considered to have failed in 11 patients, 90 days after the last i.v. IgG reinfusion (D90), because the platelet counts were comparable with pretreatment values. In contrast, a complete response was observed at D90 in five patients (mean platelet count: 184 x 10(9)/L; range: 150 to 250 x 10(9)/L) and a partial response at D90 was obtained in the remaining two patients (platelet counts: 70 and 104 x 10(9)/L). Five of the 7 responders at D90 kept a platelet count above 50 x 10(9)/L during the entire follow-up period (mean 33 months; range: 5 to 66) with no further treatment; unfortunately, no clinical or biologic criteria were found to be predictive of the long-term response. This study shows that an i.v. IgG infusion regimen of 1 g/kg body weight could safely replace the classical 2 g/kg body weight dosage, at least in patients who do not have life-threatening thrombocytopenia. Moreover, repeated i.v. IgG reinfusion could be an alternative for AITP patients in whom splenectomy is contraindicated.

An Individual Platelet Count Set-Point in ITP: A Concept Learned from Patients with Mild Thrombocytopenia and a Good Response to IVIg or Corticosteroids.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3926-3926
Author(s):  
Donald M. Arnold ◽  
Jane C. Moore ◽  
James W. Smith ◽  
John G. Kelton
Keyword(s):  
Platelet Count ◽  
Invasive Procedure ◽  
Platelet Glycoprotein ◽  
Platelet Destruction ◽  
Specific Test ◽  
Baseline Platelet Count ◽  
Set Point ◽  
Platelet Counts ◽  
Count Response ◽  
Platelet Autoantibodies

Abstract Background: Immune thrombocytopenic purpura (ITP) is a heterogeneous disease caused by both increased platelet destruction and decreased platelet production. Thrombocytopenia is typically severe, and in the absence of a sensitive and specific test, a platelet count response to intravenous immune globulin (IVIg) or corticosteroids is diagnostic. Patients with mild thrombocytopenia (platelets 50 – 150 × 109/L) may have ITP, non-immune thrombocytopenia or a low-normal platelet count. The diagnostic value of platelet autoantibodies for such patients is not known. Methods: We studied the platelet count responses of 6 patients with mild thrombocytopenia who were treated with either IVIg or corticosteroids. Baseline platelet count was defined as the mean of the 2 lowest, consecutive platelet counts that were within 15% of each other. The peak platelet count was the highest recorded platelet count measured within 1 month of treatment. For most patients, the dose of IVIg was 1g/kg ×1, and the dose of prednisone was 1mg/kg for 2 – 4 weeks. Complete response was defined as a peak platelet count that was at least 2x baseline; a partial response was defined as a peak platelet count 1.5 – 2x baseline; below that was not considered a response. Platelet glycoprotein IIb/IIIa and Ib/IX autoantibodies were determined by the antigen capture assay using platelet lysates prepared from samples collected prior to treatment. An OD &gt;0.4 was considered positive. Results: Five patients with mild thrombocytopenia received 5 treatments with IVIg and 2 treatments with corticosteroid (2 patients received IVIg on 2 separate occasions). The indications for treatment were: planned invasive procedure (n=5), pregnancy/delivery (n=1), and treatment of multiple sclerosis (n=1). Patients were followed for a median of 1.6 years (range 0.6 – 3 years). Median baseline platelet count prior to treatment was 70 ×109/L (range 57 – 79 ×109/L). A platelet count response was observed following all 7 treatments; including 5 complete responses and 2 partial responses. Median peak platelet count was 180 ×109/L (range 115 – 297 ×109/L). Post-treatment platelet counts returned to within 15% of pre-treatment values following 6 of 7 treatments after a median of 3 months (range 1 week – 5 months). Of the 3 patient tested, none had anti-GP IIb/IIIa or anti-Ib/IX autoantibodies. Interpretation: A good response to IVIg (or steroid) treatment confirmed the immune nature of mild thrombocytopenia in this cohort and should be used as the gold standard to evaluate the test characteristics of platelet autoantibodies. We observed that some patients with mild ITP have an individual platelet count “set-point” which remained relatively stable over time. Although further testing is required, this concept implies that in some patients, there is a regulated balance between platelet destruction and underproduction.

Use of Eltrombopag after Romiplostim in Primary ITP Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2790-2790
Author(s):  
Tomás José González-López ◽  
Cristina Pascual ◽  
María Teresa Álvarez-Román ◽  
Fernando Fernández-Fuentes ◽  
Blanca Sánchez-González ◽  
...  
Keyword(s):  
Platelet Count ◽  
Side Effects ◽  
Complete Remission ◽  
Adverse Events ◽  
Response Rate ◽  
Conflicts Of Interest ◽  
Initial Response ◽  
Complete Response ◽  
Oral Drug ◽  
Initial Response Rate

Abstract Background: The trombopoietin receptor agonists (TRAs) romiplostim and eltrombopag are effective and safe in the treatment of chronic immune thrombocytopenia (ITP). However, when no response is achieved or when adverse events occur with one TRA the value of the sequential use of romiplostim and eltrombopag has not been clearly established. Here we have evaluated the efficacy and tolerance of using eltrombopag after romiplostim in ITP. Methods: Fifty-one primary ITP patients (aged 18 years or more) who had been sequentially treated first with romiplostim and then with eltrombopag in the Spanish Eltrombopag Registry were retrospectively evaluated. In accordance with the usual standards, complete response was defined as a platelet count of 100x109/L and a response as a platelet count of 30x109/L or a count of at least twice the initial (pre-treatment) value. This study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee. Results: The median age of our cohort was 49 [range, 18–83] years. There were 32 women and 19 men. According to the standard definition, patients were allocated to newly diagnosed (n=2), persistent (n=5) and chronic (n=44) ITP groups. The median number of therapies prior to administration of eltrombopag was 4 [range, 2–9], including splenectomy (39%), rituximab (33%) and romiplostim (100%). The median duration of romiplostim use before switching to eltrombopag was 12 (IQR 5–21) months. The reasons for switching from the romiplostim to eltrombopag were: lack of efficacy of romiplostim (n=25), patient's preference (n=16), platelet-count fluctuation (n=6), and side-effects (n=4). The initial response rate to eltrombopag was 41/51 (80.5%), including 67% (n=34) of cases with complete remission. After a median follow-up of 13 months with eltrombopag, 39 patients maintained their response. When eltrombopag was used for patients who were refractory to the maximum romiplostim dose the initial response rate of eltrombopag was 25%. However, 83% of patients who relapsed after their initial response to romiplostim responded to eltrombopag. Sixteen romiplostim responders requested their physicians to switch them to eltrombopag because they preferred an oral drug. The efficacy was maintained after switching in all 16 patients. In the platelet-count fluctuation group, the initial response rate was also 100%. All 4 patients who were switched to eltrombopag because they experienced side-effects of romiplostim achieved complete remission with eltrombopag and their adverse events were resolved. 16 / 51 (33%) patients experienced one or more adverse event during treatment with eltrombopag. The frequency of grade 3–4 adverse events during treatment with eltrombopag was 9.8%. Conclusion: The use of eltrombopag after romiplostim for treating ITP is effective and safe. The reason for discontinuing romiplostim was associated with the response to eltrombopag. Disclosures No relevant conflicts of interest to declare.

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