scholarly journals A Phase II Study to Investigate the Efficacy and Safety of Eltrombopag in Combination with Dexamethasone As First-Line Treatment in Adult Patients with Newly Diagnosed Primary ITP (XPAG-ITP)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 36-37
Author(s):  
Axel Matzdorff ◽  
Mascha Binder ◽  
Falk Nimmerjahn ◽  
Oliver Meyer ◽  
Mathias J. Rummel ◽  
...  
Keyword(s):  
Treatment Discontinuation ◽  
Sustained Response ◽  
Adult Patients ◽  
High Dose ◽  
Newly Diagnosed ◽  
Platelet Counts ◽  
High Dose Dexamethasone ◽  
Short Course ◽  
Proliferation And Differentiation ◽  
History Of

BACKGROUND: Eltrombopag is an oral, small-molecule, non-peptide thrombopoietin receptor agonist (TPO-RA) that increases hematopoiesis by inducing proliferation and differentiation of early bone marrow progenitor cells leading to increased platelet production (Erickson-Miller et al., 2010, Sun et al., 2012). Eltrombopag has demonstrated efficacy in adult and pediatric patients with immune thrombocytopenia (ITP) and has a well-established safety profile. It is approved in Europe for the treatment of thrombocytopenia, from 6 months following diagnosis, in patients with primary ITP who are refractory to other treatments (e.g. corticosteroids, immunoglobulins). The efficacy of eltrombopag for achieving hemostatic platelet counts (≥ 50 × 109/L) in previously treated adult ITP patients with more than 6 months' disease duration is around 80% (Wong et al., 2017). However, there is insufficient data on safety and efficacy of TPO-RAs in newly diagnosed ITP patients. AIM: The aim of this trial (NCT04346654; CETB115JDE01) is to compare the ability of eltrombopag in combination with a short course of high-dose dexamethasone to induce a sustained response off treatment in comparison to dexamethasone monotherapy in newly diagnosed primary ITP patients. METHODS: This is a Phase II, multicenter, randomized (1:1), open-label study (see Figure 1). Arm A: Eltrombopag + short course of high-dose dexamethasoneArm B: 1-3 cycles of high-dose dexamethasone Adult patients with newly diagnosed primary ITP who have platelet counts < 30 × 109/L and require treatment will be screened, and if eligible, will be randomized to either Arm A or Arm B. The study will be conducted in the following periods: Screening Period: Patients will be screened based on the inclusion and exclusion criteria specified below Treatment / Tapering Period: Arm A: Patients will receive eltrombopag in combination with a short course of high-dose dexamethasone beginning at day 1. The dose of dexamethasone will be 40 mg QD (daily; quaque die) for 4 consecutive days and limited to 1 cycle. The starting dose of eltrombopag will be 50 mg QD in order to achieve the target platelet count of ≥ 50 × 109/L. Patients who reach platelet counts ≥ 30 × 109/L and maintain counts ≥ 30 × 109/L during the tapering phase (week 20 - week 26) will be eligible for treatment discontinuation starting from week 26. During the tapering phase, eltrombopag will be decreased by 25 mg every 2 weeks to a minimum dose of 25 mg every other day for all patients. Arm B: Treatment in the control arm consists of 1-3 cycles of high-dose dexamethasone administered orally at a dose of 40 mg QD for 4 consecutive days at 4 weeks intervals. Patients will be treated up to 12 weeks during the treatment period with dexamethasone. If the platelet counts are > 150 × 109/L no further course of dexamethasone will be given. Patients who reach platelet counts ≥ 30 × 109/L and maintain counts ≥ 30 × 109/L after 1-3 cycles of dexamethasone treatment will be eligible for treatment discontinuation. Observation period: After completion of the treatment period, patients will be observed for sustained response off treatment defined as: maintain platelet counts ≥ 30 × 109/L after treatment discontinuation and no bleeding events ≥ Grade II and without the use of any rescue therapy until week 52 and week 78 respectively, after study start The study is designed to include 106 adult patients with newly diagnosed primary ITP at 25 sites in Germany. Patients meeting any of the following criteria are not eligible for inclusion in this study: Previous history of treatment for ITPPatients with diagnosis of secondary thrombocytopeniaPatients who have life threatening bleeding complications per physician´s discretionPatients with a history of thromboembolic events or known risk factors for thromboembolism The primary objective is the rate of sustained responses off treatment at 52 weeks. Key secondary objectives include the duration of sustained response off treatment, the rate of sustained response off treatment at 78 weeks as well as patient-oriented outcomes for health-related quality of life. Currently, the study is recruiting patients, expected to be completed by 2021. CONCLUSION: This trial will evaluate the potential of eltrombopag in combination with steroids to increase the rate of sustained response off treatment in comparison to steroids alone in patients with previously untreated primary ITP. Disclosures Matzdorff: Novartis Oncology:Consultancy, Other: Honoraria paid to institution;Amgen GmbH:Consultancy, Other: Honoraria paid to institution;Grifols Deutschland GmbH:Consultancy, Other: Honoraria paid to institution;Swedish Orphan Biovitrium GmbH:Consultancy, Other: Honoraria paid to institution;UCB Biopharma SRL:Consultancy, Other: Honoraria paid to institution;Roche Pharma AG:Other: Family stockownership.Binder:DGHO:Honoraria, Other: Speaker Activity;Amgen GmbH:Honoraria, Other: Speaker Activity;Deutsche Krebsgesellschaft:Honoraria, Other: Speaker Activity;Merck Serono GmbH:Honoraria, Other: Speaker Activity;OSHO:Membership on an entity's Board of Directors or advisory committees;Medconcept GmbH:Honoraria, Other: Speaker Activity;Tumorzentrum Anhalt:Honoraria, Other: Speaker Activity;Janssen-Cilag GmbH:Honoraria, Other: Speaker Activity;DFG:Research Funding;Art tempi:Honoraria, Other;Sanofi-Aventis Deutschland:Honoraria, Other;Uniklinikum Hamburg:Honoraria, Other;event lab GmbH:Honoraria, Other: Speaker Activity.Nimmerjahn:Novartis Pharma GmbH:Honoraria.Meyer:Amgen GmbH:Honoraria;Novartis Pharma GmbH:Honoraria;Grifols Germany:Consultancy, Honoraria.Rummel:Roche:Honoraria;Janssen:Honoraria;Novartis Pharma GmbH:Honoraria;Celgene:Consultancy, Honoraria;Amgen GmbH:Honoraria.Tesanovic:Novartis Pharma GmbH:Current Employment.Sauer:Novartis Pharma GmbH:Current Employment. OffLabel Disclosure: Eltrombopag is an oral, small-molecule, non-peptide thrombopoietin receptor agonist (TPO-RA) that increases hematopoiesis by inducing proliferation and differentiation of early bone marrow progenitor cells leading to increased platelet production (Erickson-Miller et al 2010, Sun et al 2012). Eltrombopag has demonstrated efficacy in adult and pediatric patients with ITP and has a well-established safety profile. It is approved in Europe for the treatment of thrombocytopenia, from 6 months following diagnosis, in patients with primary ITP who are refractory to other treatments (e.g. corticosteroids, immunoglobulins).

scholarly journals A Phase II Study to Investigate the Efficacy and Safety of Eltrombopag in Combination with Dexamethasone As First-Line Treatment in Adults Patients with Newly Diagnosed Primary ITP (XPAG-ITP)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3151-3151
Author(s):  
Mascha Binder ◽  
Axel Matzdorff ◽  
Falk Nimmerjahn ◽  
Mathias Rummel ◽  
Oliver Meyer ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Treatment Discontinuation ◽  
Sustained Response ◽  
High Dose ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Platelet Counts ◽  
High Dose Dexamethasone ◽  
Short Course ◽  
History Of

Abstract BACKGROUND: Eltrombopag is an oral, small-molecule, non-peptide thrombopoietin receptor agonist (TPO-RA) that increases hematopoiesis by inducing proliferation and differentiation of early bone marrow progenitor cells leading to increased platelet production (Erickson-Miller et al., 2010, Sun et al., 2012). Eltrombopag has demonstrated efficacy in adult and pediatric patients with immune thrombocytopenia (ITP) and has a well-established safety profile. It is approved in Europe for the treatment of thrombocytopenia, from 6 months following diagnosis, in patients with primary ITP who are refractory to other treatments (e.g. corticosteroids, immunoglobulins). The efficacy of eltrombopag for achieving hemostatic platelet counts (≥ 50 × 10 9/L) in previously treated adult ITP patients with more than 6 months' disease duration is around 80 % (Wong et al., 2017). However, there is insufficient data on safety and efficacy of TPO-RAs in newly diagnosed ITP patients. AIM: The aim of this trial (NCT04346654; CETB115JDE01) is to compare the ability of eltrombopag in combination with a short course of high-dose dexamethasone to induce a sustained response off treatment in comparison to dexamethasone monotherapy in newly diagnosed primary ITP patients. METHODS: This is a Phase II, multicenter, randomized (1:1), open-label study (see Figure 1). Arm A: Eltrombopag + short course of high-dose dexamethasone Arm B: 1-3 cycles of high-dose dexamethasone Adult patients with newly diagnosed primary ITP who have platelet counts < 30 × 10 9/L and require treatment will be screened, and if eligible, will be randomized to either Arm A or Arm B. The study will be conducted in the following periods: Treatment / Tapering Period: Arm A: Patients will receive eltrombopag in combination with a short course of high-dose dexamethasone beginning at day 1. The dose of dexamethasone will be 40 mg QD (daily; quaque die) for 4 consecutive days and limited to 1 cycle. The starting dose of eltrombopag will be 50 mg QD in order to achieve the target platelet count of ≥ 50 × 10 9/L. Patients who reach platelet counts ≥ 30 × 10 9/L and maintain counts ≥ 30 × 10 9/L during the tapering phase (week 20 - week 26) will be eligible for treatment discontinuation starting from week 26. During the tapering phase, eltrombopag will be decreased by 25 mg every 2 weeks to a minimum dose of 25 mg every other day for all patients. Arm B: Treatment in the control arm consists of 1-3 cycles of high-dose dexamethasone administered orally at a dose of 40 mg QD for 4 consecutive days at 2-4 week intervals. Patients will be treated up to 12 weeks during the treatment period with dexamethasone. If the platelet counts are > 150 × 10 9/L no further course of dexamethasone will be given. Patients who reach platelet counts ≥ 30 × 10 9/L and maintain counts ≥ 30 × 10 9/L after 1-3 cycles of dexamethasone treatment will be eligible for treatment discontinuation. Observation period: After completion of the treatment period, patients will be observed for sustained response off treatment defined as: maintain platelet counts ≥ 30 × 10 9/L after treatment discontinuation and no bleeding events ≥ Grade II and without the use of any rescue therapy until week 52 and week 78 respectively, after study start The study is designed to include 106 adult patients with newly diagnosed primary ITP at 30 sites in Germany. Patients meeting any of the following criteria are not eligible for inclusion in this study: Previous history of treatment for ITP except 3 days of ITP rescue medication within 7 days before study randomization Patients with diagnosis of secondary thrombocytopenia Patients who have life threatening bleeding complications per physician´s discretion Patients with a history of thromboembolic events or known risk factors for thromboembolism The primary objective is the rate of sustained responses off treatment at 52 weeks. Key secondary objectives include the duration of sustained response off treatment, the rate of sustained response off treatment at 78 weeks as well as patient-oriented outcomes for health-related quality of life. Currently, the study is recruiting patients, expected to be completed by 2022. CONCLUSION: This trial will evaluate the potential of eltrombopag in combination with steroids to increase the rate of sustained response off treatment in comparison to steroids alone in patients with previously untreated primary ITP. Figure 1 Figure 1. Disclosures Binder: Deutsche Krebsgellschaft, Medconcept GmbH, event Lab. GmbH: Honoraria, Other: Speaker Activity; Amgen GmbH, Janssen-Cilage GmbH, DGHO, Art tempi, Tumorzentrum Anhalt MD, Uniklinikum Hamburg, Sanofi Aventis: Honoraria, Other: Speaker Activity. Matzdorff: Amgen: Consultancy, Honoraria; Argenx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Grifols: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Current holder of individual stocks in a privately-held company; UCB: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Meyer: Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Grifols: Consultancy, Honoraria; SOBI: Consultancy, Honoraria. Tesanovic: Novartis Pharma GmbH: Current Employment. Sauer: Novartis Pharma GmbH: Current Employment. OffLabel Disclosure: Eltrombopag is approved in Europe for the treatment of thrombocytopenia, from 6 months following diagnosis, in patients with primary ITP who are refractory to other treatments (e.g. corticosteroids, immunoglobulins). In this study Eltrombopag will be administered as first-line therapy in ITP.

scholarly journals Conventional Oral Prednisone Versus High-Dose Dexamethasone for Management of Adult Immune Thrombocytopenia: A Prospective Randomized Multicenter Clinical Trial

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1455-1455
Author(s):  
Yu Wei ◽  
Xuebin Ji ◽  
Jingxia Wang ◽  
Enqin Yang ◽  
Zhengcheng Wang ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Response Rate ◽  
Oral Prednisone ◽  
Sustained Response ◽  
High Dose ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
First Line ◽  
High Dose Dexamethasone

Abstract Introduction Oral prednisone (PDN) is conventional standard initial management for adult immune thrombocytopenia (ITP). In recent years single arm studies propose that high-dose dexamethasone (HD-DXM) improves response rate and remission duration and reduces adverse effects, though a randomized trial demonstrated no superiority of HD-DXM. It still lacks evidence-based conclusion on which one is better in efficacy and safety. We conducted a prospective randomized multicenter clinical trial to compare the efficacy and safety of HD-DXM and PDN as first-line strategy for adult newly diagnosed ITP. Methods We enrolled adult newly diagnosed ITP patients aging between 18 and 80 years, peripheral PLT count <30x109/L or with bleeding symptoms. Diagnosis of ITP and definition of newly diagnosed ITP followed international working group report and ASH evidence-based guideline. A 1:1 randomization was assigned between HD-DXM and PDN arm. In HD-DXM arm, dexamethasone was administered orally at 40mg/d for 4 consecutive days. If PLT count remained or dropped below 30x109/L by day 10, another four-day course of HD-DXM was given. Patients received prednisone orally at 1.0mg/kg/d for no more than 28 days in PDN arm, and then tapered rapidly to minimized maintenance dosage of <15mg/d in responders or stop in non-responders. Early response was evaluated according to criteria mentioned above. We defined sustained response as PLT count maintaining above 30x109/L for 6 months or more. Responders underwent follow-up for at least 6 months or until relapse. Adverse effects were recorded for analysis of safety. Informed consent was obtained from all enrolled patients in accordance with the Declaration of Helsinki. This study was approved by Ethics Committee of each participating site and registered at http://clinicaltrials.gov/ as NCT01356511. Results From Jan 2011 to May 2014, 182 newly diagnosed adult patients were enrolled from 9 sites over Shandong Province, China, with 92 randomized to HD-DXM arm (62 females and 30 males; age median 43, range 18~73 years) and 90 to PDN arm (68 females and 22 males; age median 44.5, range 18~76 years). Baseline PLT count were 8.93±8.19 (HD-DXM arm) and 10.60±8.67 (PDN arm) x109/L, respectively. Overall response rate in HD-DXM arm was 84.8% (78/92) with 52.2% (48/92) CR, while in PDN arm 74.4% (67/90) and 28.9% (26/90). HD-DXM arm showed similar overall response (P=0.099) but higher CR rate (P=0.002). HD-DXM arm also demonstrated shorter time to response (3.21±1.35 vs. 5.97±4.28 days, P=0.001). 149 patients were available for evaluation of sustained response, 76 in HD-DXM arm and 73 in PDN arm, with follow-up of a median of 10(1-40) and 12(1-39) months, respectively. There was no statistically significant difference between the two arms in sustained response rate (39.5% vs. 49.3%, P=0.251). Generally both treatments were well tolerated. Adverse effects were recorded (HD-DXM/PDN), including hyperglycemia (3/5), hypertension (3/3), peptic ulcer (1/3), gaining weight (0/4), and infection trend (0/2). Conclusion One or two courses of HD-DXM demonstrated higher CR rate and shorter time to response than PDN. HD-DXM could be a better first-line choice for adult ITP. Table 1. Characteristics of patients in HD-DXM and PDN arm Parameter HD-DXM PDN No. of patients 92 90 Age, median (range) 43 (18 - 73) 44.5 (18 - 76) Gender, female/male 62/30 68/22 Baseline platelet count, x109/L 8.93±8.19 10.60±8.67 Disclosures No relevant conflicts of interest to declare.

High Dose Dexamethasone Vs. Conventional Dose Prednisolone for Adults with Immune Thrombocytopenia: a Prospective Multicenter Phase III Trial.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3687-3687 ◽  
Author(s):  
Sung Hwa Bae ◽  
Hun-Mo Ryoo ◽  
Won Sik Lee ◽  
Young Don Joo ◽  
Kyoo Hyung Lee ◽  
...  
Keyword(s):  
Platelet Count ◽  
Initial Treatment ◽  
Immune Thrombocytopenia ◽  
Response Rate ◽  
Sustained Response ◽  
Adult Patients ◽  
Phase Iii ◽  
High Dose ◽  
Sustained Response Rate ◽  
High Dose Dexamethasone

Abstract Abstract 3687 Background: Prednisolone at a dose of 1 mg/kg/day (PRD) for 2 to 4 weeks is administered as front-line therapy to most adult patients with immune thrombocytopenia (ITP) who need to be treated. Recent results from 2 large single arm studies suggest high dose dexamethasone (DEX) as first-line treatment may produce a high sustained response rate. Therefore, we conducted prospective randomized trial comparing DEX with PRD as initial treatment of adult patients with newly diagnosed ITP. Methods: We did a randomized multicentre trial based on a 1:1 design. We enrolled treatment-naïve patients, 16 years or older, with a diagnosis of ITP according to the practice guidelines of the American Society of Hematology and a platelet count of 30×109/L or less. Patients with ITP were randomly assigned to receive either DEX 40 mg/day on day 1–4 (If the platelet count dropped below 3×109/L within the first six months, another four-day course of DEX was given) or PRD 1mg/kg/day for 4 weeks. The primary object of this study was the sustained response (platelet count>30×109/L after 6 months) rate. Second objectives are response rate at 4 weeks, predictors of steroid response, and toxicity. This study is registered at http://clinicaltrials.gov as NCT00451594. Results: From September 2005 to December 2009, 151 adults with ITP were randomly assigned (76 patients in the DEX arm, 75 patients in the PRD arm). Overall demographics were balanced between arms; Median age 44 years old (DEX:PRD 44 years old:44 years old); 69.5% female (DEX:PRD 73.7%:65.3%); median initial platelet count 17×109/L (DEX:PRD 16×109/L:17×109/L). Of 151 enrolled patients, 117 patients (57 patients in the DEX arm, 60 patients in the PRD arm) were evaluable in terms of sustained response. Sustained response rate by intention-to-treat (ITT) and per protocol were 25.0% and 33.3% in the DEX arm, 36.0% and 45.0% in the PRD arm, respectively (p=0.33 by ITT). Eight patients in the DEX arm and 17 patients in the PRD arm had a sustained platelet counts more than100×109/L. Fifteen patients had a sustained response after a single course of DEX and 6 patients among them required no further treatment during two to four year follow up. Median time to relapse in patients who had a sustained response was 1320 days and 1140 days, respectively. The response rate at day 28 was 68.2% in the DEX arm and 81.2% in the PRD arm. Pre-treatment platelet count was higher in patients who achieved sustained response (responder vs. non-responder: 17.1±7.8×109/L vs. 15.9±8.9×109/L). Eleven patients in the DEX arm and 8 patients in the PRD arm received splenectomy. Both treatments were well tolerated. Three patients represented side effects that were severe enough to discontinue the treatment in the PRD arm, including pneumonia (1), hyperglycemia (1), and myalgia (1). Six patients receiving DEX and 5 patients receiving PRD had G3 or more hyperglycemia. Conclusion: One or two courses of DEX were not more effective than PRD in adults with ITP. However, 19.7% of adult ITP had a sustained response with a single course of DEX. Initial treatment with DEX could be useful for identifying patients who may not require prolonged steroid treatment. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Immune Thrombocytopenia Associated with COVID-19 - Case Series

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-14
Author(s):  
Ramil Fatkhullin ◽  
Vasily Shuvaev
Keyword(s):  
Immune Thrombocytopenia ◽  
Meta Analysis ◽  
Case Series ◽  
Cervix Uteri ◽  
First Episode ◽  
High Dose ◽  
Platelet Response ◽  
Pulmonary Infiltrates ◽  
High Dose Dexamethasone ◽  
History Of

Increased numbers of COVID-19 infection make the study of its systemic manifestations more and more important. Despite of SARS-Cov-2 main clinical respiratory syndrome other clinical infection signs as immune thrombocytopenia without respiratory failure were identified. We have seen case series of patients with thrombocytopenia and active COVID-19 infection during present epidemic outbreak. Patient 1, female, 31 years old was admitted at our hospital with ecchymoses, epistaxis, gingival hemorrhage and metrorrhagia. There were also signs of COVID-19 infection - fever up to 40oC, short of breathes with room air. The pulmonary infiltrates about to 25% were revealed by CT scan. The CBC parameters were as follows: WBC 8.9x109/l, Hb 11,2 g/dl, PLT 3 x109/l by microscopy. The patient was treated with high-dose dexamethasone 40 mg QD for 4 days. The treatment resulted to stable complete platelet response as 189x109/l in fourteen days after start of therapy. At that time, the cancer in situ of cervix uteri there was revealed by gynecologic examination, that was successfully local treated. Patient 2, female 30 years old presented epistaxis, metrorrhagia, cutaneous and gingival hemorrhagic syndrome as previous patient. There were WBC 6.4x109/l, Hb 12,6 g/dl, PLT 3x109/l by microscopy in CBC. She had no respiratory signs and abnormality in pulmonary CT. The COVID-19 infection was identified by PCR and antibody screening. The patient also received high-dose dexamethasone 40 mg QD for 4 days and yielded of platelet elevation to 25x109/l with no hemorrhagic syndrome in five days of treatment. Patient 3, female 68 years old with chronic course of immune thrombocytopenia and resistance to glucocorticoid, after splenectomy and presence of HBsAg. All relapses of thrombocytopenia in this patient were associated with virus infection. The first episode was in 2009, patient was treated with glucocorticoid with no effect. The complete platelet response was achieved after splenectomy. The relapse occurred in 2015 and was associated with acute respiratory distress syndrome (probably H7N9 flu). There treatment with prednisone 1 mg/day resulted to complete platelet response. At present time, the COVID-19 infection on this patient manifested with 75% of pulmonary volume lesions. At the recovery (25% of pulmonary infiltrates) the relapse of immune thrombocytopenia with cutaneous bleeding occurred. In CBC there were WBC 5.9x109/l, Hb 15,1 g/dl, PLT 5x109/l by microscopy. Given that history of therapy we treated this patient with high-dose dexamethasone 40 mg QD for 4 days and romiplostime 2 mqg/kg. The complete resolution of hemorrhagic signs and platelet response (65x109/l) was reached in seven days of treatment. Discussion. The virus-associated thrombocytopenia is usual in common practice. In recent COVID-19 infection outcome meta-analysis (G. Lippi et al. Clinica Chimica Acta 506 (2020) 145-148) the platelet count was significantly lower in severe course of disease. The presence of platelet below the lower limit was associated with fivefold of risk of severe COVID-19 and was a factor of mortality. The platelet decline could be as sign of disease worsening at one hand and have an own risk of mortality by bleeding at other hand. There is a need for guideline to thrombocytopenia management in COVID-19 patients. Now we are continuing to search and include the patients with COVID-19 infection and thrombocytopenia in our study. Disclosures Shuvaev: Novartis:Honoraria, Speakers Bureau;BMS:Honoraria, Speakers Bureau;Pfizer:Honoraria, Speakers Bureau.

scholarly journals EPID-21. THE NATIONAL SPECTRUM OF NEWLY-DIAGNOSED BRAIN TUMORS IN ADULT PATIENTS VARIES SIGNIFICANTLY BY PATIENT DEMOGRAPHICS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi79-vi79
Author(s):  
Matthew Torre ◽  
Mustafa Ascha ◽  
Maya Harary ◽  
Timothy Smith ◽  
Ayal Aizer ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Patient Characteristics ◽  
Intracranial Tumor ◽  
Adult Patients ◽  
Intracranial Tumors ◽  
Newly Diagnosed ◽  
Patient Demographics ◽  
Common Diagnosis ◽  
History Of ◽  
Tumor Types

Abstract INTRODUCTION Herein we examine the epidemiology and outcomes of the entire spectrum of intracranial tumors in the contemporary era. METHODS Adult patients (≥20yo) presenting between 2010–2015 where the first evidence of cancer involves an intracranial tumor were queried from the National Cancer Database, which comprises >70% of cancers newly-diagnosed in the U.S. Tumor types were classified by WHO2016 ICD-O3, and stratified by patient characteristics. RESULTS 361,841 adults without a history of cancer presented with intracranial tumors between 2010–2015. Across all ages, these were comprised of 1) brain metastases (BMs; 25%: 29% in males vs. 23% in females); 2) meningiomas (25%: 15% in males, but 34% in females) including atypical (n=4,565) and anaplastic (n=833); 3) diffuse infiltrative gliomas (21%: 26% in males vs. 17% in females), mostly GBMs (14%); followed by 4) sellar (14%), 5) cranial nerve (6%), and PCNSL (3%) tumors. The remaining types each comprised ≤2 % of brain tumors, including mesenchymal non-meningothelial tumors (2%), intracranial ependymal (0.8%), mixed neuronal-glial (0.7%), circumscribed “other astrocytomas” (0.6%, mostly pilocytic astrocytomas n=1,307 and PXAs n=272), CNS embryonal (0.3%), pineal (0.2%), GCTs (0.1%), and choroid plexus (0.1%) tumors. In the 91,686 patients presenting with a BM, the most common primaries were lung adenocarcinoma (39%), lung SmallCC (14%), lung SqCC (8%), breast (8% of females), melanoma (3%), kidney (3%), colorectal (2%), and esophageal (1%). The distributions of brain tumor types differed significantly by age, sex, race/ethnicity, and insurance status. CONCLUSIONS In adult patients where the first manifestation of cancer includes an intracranial tumor, the most common diagnosis is either metastatic disease (predominantly from NSCLC) in males or benign meningiomas in females; but varies substantially by age group. Notably, our results adjust the traditional teaching that half of all new brain masses are BMs, which in fact represent only ~25% of new intracranial masses.

scholarly journals High Dose Methylprednisolone: Effective in Pregnancy Associated Post-splenectomy Refractory Chronic Immune Thrombocytopenic Purpura

2014 ◽  
Vol 9 (1) ◽  
pp. 64-66
Author(s):  
A Singh ◽  
A Solanki
Keyword(s):  
Past History ◽  
Oral Steroid ◽  
High Dose ◽  
Third Trimester ◽  
Thrombocytopenic Purpura ◽  
Platelet Counts ◽  
Male Baby ◽  
High Dose Methylprednisolone ◽  
History Of ◽  
Acute Crisis

We present a case of 23 years multigravid woman (G2P0+1) with chronic idiopathic thrombocytopenic purpura (ITP), refractory to treatment in forms of oral steroid, dapsone, azathioprine and splenectomy. She presented to the hospital in third trimester of pregnancy, with reduced platelet counts and purpuric rashes over abdomen and both upper extremeties. There was a past history of spontaneous abortion at 18 weeks. The patient responded to intravenous high dose methylprednisolone (HDMP) infusion leading to delivery of full term male baby. The baby also required treatment for thrombocytopenia with intravenous immunoglobulin (IVIG). This case lays down the importance of HDMP in form of using it effectively in managing acute crisis of low platelet counts in pregnant patients with ITP refractory to splenectomy. DOI: http://dx.doi.org/10.3126/njog.v9i1.11192 NJOG 2014 Jan-Jun; 2(1):64-66

Superiority of Lenalidomide-Dexamethasone Versus Thalidomide-Dexamethasone as Initial Therapy for Newly Diagnosed Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3884-3884
Author(s):  
Francesca Gay ◽  
Suzanne Hayman ◽  
Martha Q. Lacy ◽  
Francis Buadi ◽  
Morie A Gertz ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Initial Therapy ◽  
High Dose ◽  
Toxicity Profile ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Intention To Treat ◽  
High Dose Dexamethasone ◽  
Grade 3

Abstract Abstract 3884 Poster Board III-820 Background and Objective Thalidomide/dexamethasone (thal/dex) combination has shown high activity in newly diagnosed multiple myeloma (MM) (Rajkumar SV. at al, J Clin Oncol 2006;24:431-436). In newly diagnosed patients, lenalidomide/dexamethasone (len/dex) has demonstrated superiority compared with high-dose dexamethasone alone (Zonder JA et al, Blood 2007;110:77). Although both thal/dex and len/dex are active in newly diagnosed MM, no randomized trial has been reported comparing these two regimens, and unfortunately none are ongoing or planned. We compared the efficacy and the toxicity of thal/dex and len/dex as primary therapy in 411 newly diagnosed MM patients treated at the Mayo Clinic. Patients and methods 411 consecutive patients seen at Mayo Clinic between 2001 and 2008, who received induction with thal/dex (n=183) or len/dex (n=288) were retrospectively studied. Thalidomide was given at a dose ranging from 100 mg/day to 400 mg/day continuously; the lenalidomide dose was 25 mg/day, days 1-21 on a 28-day cycle. All patients received dexamethasone, either at high-dose (40 mg orally on days 1-4, 9-12, and 17-20) or at low-dose (40 mg orally day 1, 8, 15, 22); each cycle was repeated every 4 weeks. In addition, a case-matched subgroup analysis that adjusted for age, gender and transplantation status was performed among patients who received high-dose dexamethasone comparing the thal/dex (n=72) and len/dex (n=72) groups. Outcome was analyzed on an intention-to-treat basis. The Chi-square or the rank sum tests were used to compare variables. Time-to-event analysis was performed using the Kaplan-Meier method and all comparisons were determined by the log-rank test and by the Cox proportional hazards model. Results On intention-to-treat analysis, of 411 patients, 80.3% versus 61.2% patients, respectively in the len/dex group and in the thal/dex group (p < 0.001), achieved at least a partial response. A significant difference between the 2 groups was found in terms of both very good partial response or better (34.2% vs 12.0%, p < 0.001) and complete response rate (13.6% vs 3.3%, p < 0.001). Duration of therapy was significantly longer in len/dex patients as compared to thal/dex patients: 36.7% vs 12.6% of patients who did not stop treatment to receive SCT were still receiving therapy at 1 year (p < 0.001).Time-to-progression was significantly better in the len/dex group than in patients receiving thal/dex (median 27.4 vs 17.2 months, HR 0.64; 95% CI 0.44-0.93; p = 0.019). Similarly, progression-free-survival was significantly higher in len/dex patients (median 26.7 vs 17.1 months, HR 0.69; 95% CI 0.48-0.98; p = 0.036). This translated into an increase in overall survival (OS) (median not reached for len/dex group compared to 57.2 months in thal/dex patients, HR 0.60; 95% CI 0.40-0.92; p = 0.018). Survival advantages were evident in patients presenting with International Staging System Stage (ISS) I/II (HR 0.57; 95% CI 0.32-1.00; p = 0.052) at diagnosis but not in patients with ISS stage III in subgroup analysis. There was a trend toward better OS in len/dex group compared to thal/dex group both for patients who underwent transplant and for patients who did not. A similar rate of patients experienced at least one grade 3 or higher adverse event (57.5% vs 54.6% in len/dex and thal/dex groups, respectively, p = 0.568). However, the toxicity profile was different in the two groups: major grade 3-4 toxicities of len/dex were hematological, in particular neutropenia (14% with len/dex vs 0.6% with thal/dex, p<0.001) while the most common toxicities in thal/dex were venous thromboembolism (15.3% vs 9.2%, p = 0.058) and peripheral neuropathy (10.4% vs 0.9%, p < 0.001). The data on efficacy and safety shown above were also confirmed in the subgroup case-matched analysis which included only high-dose dexamethasone patients. Conclusions This cohort study shows the superiority of len/dex in terms of response rates and survival, compared to thal/dex. The toxicity profile of the 2 regimens is different and len/dex treatment, although more active, was not associated with increased toxicity (grade 3-4 AEs). These data need to be carefully evaluated and randomized prospective phase III studies are necessary to confirm these results and determine the optimal initial therapy for MM. Disclosures: Off Label Use: research drugs in combination to standard care. Lacy:celgene: Research Funding. Gertz:celgene: Honoraria; genzyme: Honoraria; millenium: Honoraria; amgen: Honoraria. Kumar:celgene: Research Funding; millenium: Research Funding; bayer: Research Funding; Novartis: Research Funding; Genzyme: Research Funding. Dispenzieri:celgene: Research Funding. Bergsagel:amgen: Membership on an entity's Board of Directors or advisory committees; genetech: Membership on an entity's Board of Directors or advisory committees; merck: Research Funding; celgene: Membership on an entity's Board of Directors or advisory committees. Witzig:celgene: Research Funding. Fonseca:medtronic: Consultancy; genzyme: Consultancy; celgene: Consultancy; amgen: Consultancy; BMS: Consultancy; otsuka: Consultancy. Greipp:celgene: Research Funding.

Sequential High-Dose Dexamethasone and Response Adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) Induction Chemotherapy Followed by High-Dose Chemotherapy with Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma; Open-Labelled, Multicenter Phase 2 Study (KMM-94 Study)-Interim Analysis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2044-2044
Author(s):  
Jin Seok Kim ◽  
Cheolwon Suh ◽  
June-Won Cheong ◽  
Kihyun Kim ◽  
Yang Soo Kim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Induction Chemotherapy ◽  
Induction Treatment ◽  
High Dose ◽  
Newly Diagnosed ◽  
Younger Patients ◽  
High Dose Dexamethasone

Abstract Abstract 2044 Background: Induction treatment followed by autologous stem cell transplantation (ASCT) is the standard therapy for the newly diagnosed younger patients with multiple myeloma (MM). Although new drugs such as lenalidomide or bortezomib have been shown the promising results as induction treatment, many different type of induction treatment regimens still have been used. We evaluate the efficacy and safety of the short course of high dose dexamethasone (HD dexa) and the response adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) induction chemotherapy in the newly diagnosed younger patients with MM. Methods: 107 newly diagnosed patients with MM from 21 institutions received 2nd cycles of HD dexa followed by PAD or VAD chemotherapy according to the response to the initial high dose dexamethasone. The primary endpoint was complete response (CR) + near CR rate after ASCT. Among 107 patents enrolled this study from November 2009, 25 patients (23%) have been dropped out. This trial will be continued until total 210 patients will be enrolled. The trial is registered on National Cancer Institute website, number NCT01255514. Results: One hundred seven patients (58 male, 49 female) were enrolled (median age; 56). 26 (24%) light chain disease were included. 31 (29%) patients were D-S stage II and 67 (63%) were stage III. According to the ISS, 23 (22%) patients had stage I, 51 (48%) had stage II and 33 (31%) had stage III. 26 (24%) patients had abnormal cytogenetics. There were 31% del13, 7% del17, 19% t(4;14), 15% t(14;16) and 28% t(11;14) in FISH analysis. Among the 82 evaluable patients, CR + PR rate was 48% (39/82) after 2nd cycles of HD dexa therapy. 39 patients (48%) received subsequent VAD chemotherapy and 43 patients (52%) received PAD chemotherapy. Among the 64 patients finished VAD or PAD chemotherapy, CR + PR rate was 83% (79%, 26/33 in VAD group vs. 87%, 27/31 in PAD group). 56 patients were finished ASCT until now. CR + near CR rate after ASCT were 61% (58% in VAD group vs 63% in PAD group). Mortality rate of this trial was 13% (11/82). The cause of death was disease progression (n=3), bleeding (n=1) and infections (n=7). Among 82 patients in whom VAD or PAD chemotherapy was actually performed, 1 year overall survival (OS) rate was 84.7%. 1 year survival rate was 93.8% versus 77.2% (P=0.049) with VAD versus PAD (median follow-up; 9.1 months). Conclusion: Risk adapted approach using initial steroid response showed good response results after ASCT compared with previous trial (CR + near CR rate of IFM 2005-01trial-Bortezomib+dexa induction & ASCT was 35%, J Clin Oncol. 2010;28:4621–9) The MM patients who had poor response to HD dexa also showed similar good response rate after ASCT compared with the patients who had good response to HD dexa treatment in this trial. PAD re-induction therapy after failure of initial steroid induction treatment might overcome the inferior results in the high risk MM patients. Therefore, initial steroid response adapted strategy might be the more cost-effective approach in the newly diagnosed ASCT eligible MM patients. Disclosures: No relevant conflicts of interest to declare.

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