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.

First-LINE Treatment With High-Dose Dexamethasone Terapy For Adult Primary Inmune Thrombocytopenia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1081-1081
Author(s):  
Dana Diaz-Canales ◽  
Maria Rosario Prieto-Bonilla ◽  
Maria Eva Mingot-Castellano ◽  
Ana Isabel Heiniger Mazo
Keyword(s):  
High Risk ◽  
Median Time ◽  
High Dose ◽  
Similar Response ◽  
Line Treatment ◽  
First Line ◽  
High Dose Dexamethasone ◽  
Number Of Patients ◽  
First Line Treatment

Abstract Introduction Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder with a very variable outcome. Bleeding manifestations and platelets count are considered the main criteria to start treatment in these patients. The initial recommended therapy are corticosteroids and intravenous immunoglobulin (IgsIV). The aim of our study is the description of efficacy and safety of high-dose dexamethasone (Dx) used as frontline therapy in newly diagnosed ITP patients. Methods A series of patients diagnosed in our centre from March 2009 to August 2012 has been studied. They have received first-line treatment with Dx (40 mg/d four consecutive days every 2 or 4 weeks) for 1 to 6 courses. Sex, age, cardiovascular risk factors, reasons to treat, response, courses of treatment, complications and relapse rate were recorded and analyzed. Results Our series of twenty-nine patients, 18 women (62%) and 11 men (38%), had a median age of 54 years (range 16-92 years). Twenty-five patients (86%) were treated after low platelet counts (30x 10e9 / L) with or without clinical bleeding, whereas the other four patients were treated as a surgery preparation. One patient received a reduced dose of Dx (20 mg/d x 4 days) because of comorbidities and high risk of infection. In thirteen patients, IgsIV were added to Dx in the first course (1g/kg/d x 2 days), because of high bleeding risk or more severe bleeding at diagnosis. Platelets count at baseline was 15x109/ L (range 1-29 x109/ L). Ninety-three percent of patients responded after the first course of Dx (69% complete response CR, 24% partial response PR), and 45% of the patients did not require additional Dx treatment. The median time to reach a response was 5 days since the first day of treatment (range 2-60). The sixteen patients who need more than one course received a median of 4 (range 2-10), all of them without IgsIV. After a median follow-up of 14 months (range 2-45), 69% of these patients maintained the response without further treatment. Therefore, the overall response of the series reaches 83%. After 6 courses of treatment, 5 subjects did not achieved response and were classify as corticosteroid dependent. Of these, one patient was splenectomized and at present he remains at CR after 30 months of follow up. Another patient is waiting for splenectomy, and other three received thrombopoietin analogs, remaining all them in CR under treatment. Thirteen patients received a combination of Igs and Dx in the first course due to high risk of bleeding (platelets less than 20 x 10e9/L and hemorrhagic manifestations). Eleven of them (81%) achieved response (4 PR, 7CR) at a median time of 4 days (range 2–60). After the first course of treatment, 61% (8 of 13) of patients receiving both IgsIV and Dx responded, vs 35% (5 of 16) of those treated only with Dx. This difference was not statistically significant, probably because of the small number of patients in our series. All patients treated with IgsIV and Dx in the first course got the best response after 4 cycles of dexamethasone, compared to 75% of subjects treated with Dx for 4 to 6 courses. Dx was usually well tolerated, since only 13% of the patients experienced side effects: one case of hypertension, another patient developed hyperglycemia associated to corticosteroids and other two presented mild transient steroid psychosis episodes. Infectious events were not observed. Conclusions Treatment with high-dose dexamethasone as first-line treatment for ITP is a good alternative to prednisone because it shows a high efficacy and a good safety profile. In our experience, the association of IgsIV and Dx in the first course may improve the response rate and decrease the total dose of steroids needed to achieve a similar response. Disclosures: No relevant conflicts of interest to declare.

Eltrombopag and High-Dose Dexamethasone As First Line Treatment For ITP

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3544-3544
Author(s):  
David Gomez-Almaguer ◽  
Miguel Angel Herrera-Rojas ◽  
Andres Gomez-de Leon ◽  
Olga Graciela Cantú-Rodríguez ◽  
Cesar H Gutiérrez-Aguirre ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
High Dose ◽  
Line Treatment ◽  
Front Line ◽  
First Line ◽  
High Dose Dexamethasone ◽  
Line Therapy ◽  
First Line Treatment

Abstract Introduction Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder that involves antibody and cell mediated destruction of platelets as well as suppression of their production. Prednisone is the initial standard therapy in adults1. High-dose dexamethasone as front-line therapy given as pulses of 40 mg per day for 4 consecutive days, was effective in 85% of patients, nevertheless, 50% relapsed within six months2. The prices of ITP drugs for 1 month of treatment in an adult range from prednisone; $16, eltrombopag; $5,934, intravenous immune globulin (IVIG) (80 g); $9,648, to rituximab (2 g); $15,5963. Only prednisone/dexamethasone and eltrombopag are available in oral presentation, for this reason, ambulatory treatment is an alternative for these patients. The trombopoietin receptor agonists are effective for the treatment of patients with chronic ITP, although response is dependent on continued administration. Eltrombopag is a small molecule agonist of the c-mpl (TpoR) receptor, which is the physiological target of thrombopoietin. This drug effectively raises the platelet count in adult patients (aged 18 years and over) as second/third line therapy, that is for patients refractory to corticosteroids and IVIG who have had their spleen removed or when splenectomy is not an option4. Our group, as well as others, has previously sought to improve response rates in these patients, particularly with the use of rituximab5, 6. To our knowledge neither eltrombopag nor romiplostim have been used as front line therapy in ITP, therefore the purpose of this study was to assess the efficacy of eltrombopag and dexamethasone in this setting. Patients and Methods This was a prospective, phase 2 study, using the combination of eltrombopag (50 mg PO once a day for 4 weeks) and high-dose dexamethasone (40 mg PO days 1,2,3,4) in untreated adult patients with immune thrombocytopenia or in patients with less than 7 days of treatment with corticosteroids. Complete response (CR) was defined as an increase in platelet count >100×109/L. Partial response (PR) was defined as an increase in the platelet count greater to 30 ×109/L according to standard criteria. Duration of response was considered from the day of initial administration to the first time of relapse (platelet count <30×109/L). Results Twelve consecutive patients were enrolled from June 2012 to June 2013, 6 women and 6 men. The median age at diagnosis was 50 years (range, 20 - 80 years). The median platelet count at diagnosis was 7 x 109/L (range, 2 - 29 x 109/L). Patients were followed for a median of 2.5 months (range 1.1 - 13). After steroid treatment at day +5, ten patients had responded (83.3%), five had achieved CR (41.7%), and five PR. After completing treatment with eltrombopag at day +34, all patients responded (100%), nine patients achieved CR (75%) and three PR (25%). Two patients relapsed in a median time of 39.5 days (range, 30.1 - 49), both regaining CR after treatment with another high-dose dexamethasone course and low-dose rituximab (4 doses of 100 mg every week). At 3 months follow-up 66.7% remained in CR and 33.3% in PR (n=6). At 6 months follow-up two patients remained in CR and two in PR (n=4). Time to best response achieved was 34 days from diagnosis (range, 19 – 64.1). At the end of follow-up 9 patients (75%) remained in CR and 3 patients in PR (25%). Total treatment cost per patient was $1,640 approximately. Conclusion Currently the initial treatment of ITP patients is based on prednisone or high dose dexamethasone with or without IVIG. This approach is associated with high cost and high relapse rate. The results from our pilot study suggest that high dose dexamethasone and eltrombopag are very effective as first line treatment for acute ITP in adults. This treatment is ambulatory, affordable and well tolerated; however, we still don't know if this approach will have a favorable impact on the relapse rate of this disease. Disclosures: Off Label Use: Eltrombopag as first line treatment for ITP.

Single-agent bortezomib in previously untreated multiple myeloma (MM): Results of a phase II multicenter study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7504-7504 ◽  
Author(s):  
K. Anderson ◽  
P. Richardson ◽  
A. Chanan-Khan ◽  
R. Schlossman ◽  
N. Munshi ◽  
...  
Keyword(s):  
Response Rate ◽  
Axonal Neuropathy ◽  
Single Agent ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Time To Progression ◽  
Large Fiber ◽  
Grade 3 ◽  
Dose Modifications

7504 Background: Bortezomib is effective in relapsed and/or refractory MM. This trial evaluated its efficacy and safety as monotherapy in previously untreated MM. Methods: Pts with untreated, symptomatic MM were eligible, with pts receiving concomitant steroids, platelet count < 30 × 109/L, or grade > 2 peripheral neuropathy [PN] excluded. Endpoints included response rate (RR) [Bladé criteria], time to progression, safety, incidence/severity of PN, and effect of dose modifications on PN. Pts received bortezomib 1.3 mg/m2 (d1, 4, 8, 11 every 21d) for 8 cycles. Comprehensive neurologic evaluation including electrophysiologic testing [NCS] and skin biopsy was performed in a subset of pts (n = 34). Results: Sixty-six pts (47% with stage III MM) were treated and 60 pts are evaluable for response, with an overall RR of 38% (CR 10%, PR 28%). PN was reported in 55% (36/65) pts (23 grade 1, 12 grade 2). One pt with grade 3 PN was discontinued. Other common treatment-associated adverse events reported to date include grade 1–2 fatigue in 21% (6/29), and rash in 17% (5/29) pts. Preliminary analysis shows PN improved or resolved in 75% (6/8 pts, with available follow-up data) with dose reduction. At baseline, small-fiber neuropathy (SFN) was seen in 52% (17/33) and large fiber axonal neuropathy (LFN) occurred in 9% (3/34) pts by NCS. SFN worsened in 41% (7/17) pts with baseline SFN. After completion of treatment, new SFN was seen in 33% (8/24) pts and LFN in 17% (4/24) pts by NCS. Conclusion: Single agent bortezomib is active in newly diagnosed MM pts (CR 10%), has manageable toxicity and offers a steroid-sparing approach. Underlying SFN appears more common in MM than previously appreciated and can also develop during bortezomib therapy, with symptomatic PN improving with dose modification. [Table: see text]

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 &lt; 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 &gt; 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.

Primary Female Genital Lymphoma: Prognostic and Therapeutic Considerations

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4941-4941
Author(s):  
Sara Steffanoni ◽  
Alberto Agazzi ◽  
Daniele Laszlo ◽  
Sarah Jane Liptrott ◽  
Mara Negri ◽  
...  
Keyword(s):  
Response Rate ◽  
Early Stage ◽  
Local Treatment ◽  
High Dose ◽  
First Line ◽  
Bulky Disease ◽  
First Line Therapy ◽  
Line Therapy ◽  
Female Genital

Abstract Primary Female Genital Lymphoma (PFGL) is very rare, representing 1.5% of all Non-Hodgkin’s Lymphomas (NHLs) and 0.5% of female genital malignant tumours; uterus is the main commonly genital site involved by NHL. Most PFGLs are B-cell lymphomas; usually they occur in 5th decade of life. Because of PFGL rarity, a standard treatment has not been identified yet. This is a retrospective study on 20 women with PFGL, treated at European Institute of Oncology. The median age was 52 yrs (range 30–79 yrs); at diagnosis 6 pts were asymptomatic, 11 reported pelvic symptoms and 3 B symptoms. According to the International Prognostic Index, 7 pts had low, 6 intermediate, 6 high risk and one pt not known. Eleven pts had uterine involvement, with a concomitant extension to vagina in 5 of them, ovary NHL was recognised in 4 pts, vaginal NHL in 4 pts and vulvar NHL in one pt. Diffuse large B-cell NHL (DLBCL) was diagnosed in 14 pts, marginal extranodal NHL in 3 pts and follicular in 3 pts. According to Ann Arbor staging system: 8 pts were in early stage (IE–IIE) and 12 pts in stage IVE; considering FIGO system: 11 pts were in early stage (I–II), 6 pts in stage III for regional lymph node involvement and 3 in stage IV for concomitant non-genital extranodal localization; 12 pts presented with bulky disease. At diagnosis no pts had bone marrow involvement. The diagnostic biopsy was performed by endoscopy in 13 pts and by ultrasound-guided in 2 pts, whereas 5 pts underwent laparotomy. One pt with vulva-limited marginal NHL did not receive any treatment until disease progression (PD) and transformation to DLBCL. Five pts underwent laparotomy and adjuvant chemotherapy (CT) alone (n=4) or in combination with radiotherapy (RT) (n=1); 14 pts received CT alone (n=8) or in combination with RT (n=6) as first line therapy. Anthracycline-containing CT was delivered to all pts with DLBCL (n=14) and to one pt with high grade follicular NHL, 12 of them received concurrent immunotherapy anti-CD20 (Rituximab). Central nervous system (CNS) chemo-prophylaxis with i.v. high dose methotrexate was delivered to 3 pts because of advanced or bulky disease. Two pts with follicular and 2 with marginal subtype received alkylating-containing CT alone (n=2) or with Rituximab (n=2). The Overall Response Rate (ORR) to first line therapy was 80%; the response did not improve by the addition of local treatment to CT. Three pts did not response to first line therapy: one with marginal NHL in stable disease did not receive any additional treatment because of asymptomatic disease; two with DLBCL in PD underwent salvage treatment with high dose CT and died in PD, concurrent intrathecal therapy was mandatory in one pt because of CNS relapse. Three pts with follicular NHL, in response to first line therapy, relapsed: one went on to receive maintenance Rituximab, one resulted refractory to different rescue CT regimens and died in PD, one underwent autologous bone marrow transplantation obtaining CR. After a median follow up of 51 months (range 11–164 months), 17 pts are still alive: 10 in CR and 7 in PR, 3 pts died in PD. The Overall Survival (OS) at 3 and 14 yrs was 84.8% and 42.4% respectively. According to the literature the most common histological subtype of PFGL occurred in our population was DLBCL and the most frequent genital site involved was uterus (55% of cases) [Lagoo et al. 2006]. An additional local treatment did not seem to give an advantage in terms of ORR, PFS and OS in comparison with systemic therapy alone, as stated by the literature [Signorelli et al. 2006]. Concerning the pts treated with anthracycline-containing CT with or without Rituximab (n=15), 8 pts (53%) and 5 pts (33%) achieved CR and PR respectively, 2 pts (13%) had a PD during treatment, only one pt in CR relapsed after 65 months from the first line therapy. After a median follow up of 27 months 12 pts (80%) are alive, 3 (20%) died in PD. The Response Rate and OS in the subgroup of pts that received anthracycline-containing CT resulted similar to those reported in the literature [Coiffier 2002]; therefore female genital involvement by NHL doesn’t seem to represent a negative prognostic factor.

scholarly journals High-dose dexamethasone vs prednisone for treatment of adult immune thrombocytopenia: a prospective multicenter randomized trial

Blood ◽  
2016 ◽  
Vol 127 (3) ◽  
pp. 296-302 ◽  
Author(s):  
Yu Wei ◽  
Xue-bin Ji ◽  
Ya-wen Wang ◽  
Jing-xia Wang ◽  
En-qin Yang ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Immune Thrombocytopenia ◽  
High Dose ◽  
Newly Diagnosed ◽  
First Line ◽  
Multicenter Randomized Trial ◽  
High Dose Dexamethasone ◽  
Key Points ◽  
Line Management

Key Points HD-DXM is a preferred strategy to conventional prednisone as first-line management of newly diagnosed adult primary ITP.

scholarly journals Efficacy and Safety of Generic Dasatinib As First-Line Treatment in Patients with Chronic Myeloid Leukemia in Chronic Phase: Final Analysis with 2-Year Follow-up

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3616-3616
Author(s):  
Jie Jin ◽  
Li Meng ◽  
Wenjuan Yu ◽  
Peng Liu ◽  
Xin Du ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Primary Endpoint ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
First Line ◽  
First Line Treatment

Abstract Purpose: Generic dasatinib, a second-generation tyrosine kinase inhibitor (TKI), was approved as a second-line treatment for chronic myeloid leukemia (CML) patients in chronic phase (CP) in china. We initiated a prospective, multi-center and single-arm clinical trial (NCT04925141) from May 2016 to October 2018 to evaluate efficacy and safety of generic dasatinib as first-line treatment in China. The primary endpoint was achieved, here we reported the 2 years follow-up results to see its long-term clinical benefit in Chinese patients. Methods:The study included the newly diagnosed CML-CP patients who was diagnosed by the presence of Philadelphia (Ph) chromosome and/or presence of BCR-ABL fusion gene. Key inclusion criteria were as follows: 1) Age ≥ 18 years; 2) The CML subjects in chronic phase with the Ph+ definitive diagnosis were within 6 months before the onset of administration of the study drug; 3) The ECOG performance grades of 0-2; 4) Sufficient main organ functions. All newly diagnosed patients were given 100mg/d (initial dose) of the generic dasatinib. The primary endpoint was molecular major response (MMR) calculated based on the BCR-ABL1 ≤ 0.1% at the 12th month. Secondary endpoints were proportion of subjects who achieved and maintained MMR at 3, 6, and 18 months; Cumulative MMR rates at 6, 12, and 24 months were determined. All patients were followed up through the hospital outpatient departments at second, fourth and eighth weeks, and third, sixth, ninth, twelfth, eighteenth, and twenty-fourth months. The follow-up ended on December 6, 2019. The SAS 9.2 software was utilized for all statistical analyses in this study, and the two-sided test was performed to see variances. Results: A total of 59 patients were included in this trail, with median age of 44 (19 - 70), and 7% of the subjects were at high risk based on the Sokal index for the disease prognosis. The primary endpoint MMR rate at the 12th month was 80.8% which had been published. At 12 months, the cumulative response rate (CCyR) was 85.5% (47/55) and the cumulative MMR was 76.4% (42/55). Here we are reporting the 2 years follow ups. At 24 months, the complete hematological response (CHR) was 88.4%, the cumulative MMR rate was 73.7%, the cumulative MR4.0 rate was 63.6%, the cumulative MR4.5 rate was 58.2%, and the cumulative complete molecular response (CMR) rate was 58.2%. The most common adverse events (AEs) was thrombocytopenia (42.4%) in hematology and pleural effusion (20.3%) in non-hematology, only 11.9% and 1.7% of whom were grade III~IV respectively. Conclusion: This was the first report on domestic dasatinib as the first-line treatment for CML-CP patients received a clinical benefit with 24 months in China. Safety was similar with that of the original study data. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Eltrombopag, Low-Dose Rituximab, and High-Dose Dexamethasone Combination for Patients with Newly Diagnosed Immune Thrombocytopenia: A Pilot "Total Therapy" Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1369-1369
Author(s):  
David Gomez-Almaguer ◽  
Olga Cantu-Rodriguez ◽  
Cesar Homero Gutierrez-Aguirre ◽  
Jose Carlos Jaime-Perez ◽  
Luz C. Tarin-Arzaga ◽  
...  
Keyword(s):  
Partial Response ◽  
Board Of Directors ◽  
Low Dose ◽  
Complete Response ◽  
High Dose ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
High Dose Dexamethasone ◽  
Frontline Therapy

Abstract Introduction: Immune thrombocytopenia (ITP) is an autoimmune disorder that results from platelet destruction and production suppression. Frontline-therapy includes corticosteroids, intravenous immune globulin or anti-D immunoglobulin. Single-agent treatments have not been successful in inducing prolonged remission, as relapse will occur in approximately 50% of patients. Low-dose rituximab (100 mg) has been used for the treatment of ITP, showing an activity almost similar to the 375 mg/m2 standard dose. We and others have reported sustained response rates ranging from 58% to 76% using rituximab plus dexamethasone as a frontline therapy. Eltrombopag is a thrombopoietin nonpeptide mimetic that has been shown to raise platelet count in chronic ITP, and we have previously reported eltrombopag/dexamethasone as a feasible frontline therapy for ITP reaching 100% response rates.The lack of sustained response in many adult patients with newly diagnosed acute ITP has stimulated the search for a treatment that modifies the natural course of the disease. Objetive: We aim to evaluate efficacy, safety, and response duration of low-dose weekly rituximab (100 mg weekly, four doses) plus high-dose dexamethasone (40 mg PO, days 1-4) in combination with eltrombopag (50 mg, days 1-28) as frontline therapy in newly diagnosed primary ITP in an ambulatory setting. Methods: This is an ongoing open-label, single-arm study performed in patients with newly diagnosed ITP from the Hospital Universitario Dr. Jose Eleuterio Gonzalez in Monterrey, Mexico (Clinical trials.gov NCT02834286). Eligible patients are 16 years or older, with bleeding manifestations and/or a platelet count ²30×109/L, without previous treatment. Patients are excluded if they had active infection, pregnancy, or a malignant disease. A complete blood count is performed at baseline, on days 3, 5, 7 and then weekly for 28 days, monthly until month 6, and every 3 months thereafter. Partial and complete responses are defined as an increase in platelet counts ³30×109/L and ³100×109/L, respectively. Results: Ten consecutive patients have been enrolled from March 2015 until July 2016. Median age was 37 years (16-61). Six patients were women (60%) and four were men (40%). Median platelet account at diagnosis was 7 « 109/L (range 1.2-28). Median follow-up has been 7 months (range 1-13). All patients achieved at least a partial response (PR) at a median of 4 days (range 3-14). Complete response (CR) was achieved in 9 patients in a median of 7 days (7-22); all of them were still in CR at the end of treatment (Day 28). One patient lost response at 28 days and received a second high-dexamethasone course maintaining CR. No significant adverse effects have occurred during treatment, only 1 patient reported mild myalgia. No relapses have been documented until now.Currently, 8 patients remain in CR and 2 in PR. Conclusion:This is the first trial evaluating the response of low-dose rituximab in combination with eltrombopag and high-dose dexamethasone in newly diagnosed patients with ITP.Low-dose rituximab in combination with eltrombopag and high dose dexamethasone is a feasible frontline therapy for ITP. This drug combination showed high response rates achieved very rapidly, with a low incidence of side effectsand might represent an attractive option in patients with ITP and substantial bleeding. Table Characteristics and follow-up of patients M: Male, F: Female, CR: Complete Response, PR: Partial Response Table. Characteristics and follow-up of patients. / M: Male, F: Female, CR: Complete Response, PR: Partial Response Disclosures Gomez-Almaguer: Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Tacrolimus Plus High-Dose Dexamethasone Versus High-Dose Dexamethasone Alone As First-Line Treatment for Adult Immune Thrombocytopenia: The Phase 2, Open Label, Randomized Trial (TARGET 020)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 13-13
Author(s):  
Zhuo-Yu An ◽  
Ye-Jun Wu ◽  
Yun He ◽  
Xiao-Lu Zhu ◽  
Hong-Xia Shi ◽  
...  
Keyword(s):  
Platelet Count ◽  
Combination Group ◽  
High Dose ◽  
Line Treatment ◽  
Monotherapy Group ◽  
First Line ◽  
Open Label ◽  
High Dose Dexamethasone ◽  
First Line Treatment

Abstract Introduction Immune thrombocytopenia (ITP) is an acquired, organ-specific, autoimmune disease and one of the most common bleeding disorders seriously endangering human health. Glucocorticoids and intravenous immunoglobulin are first-line treatments recommended by guidelines for patients with ITP. However, approximately 50%-85% of patients relapse during the first year of treatment. In addition, long-term use of glucocorticoids increases the risk for dose- and time-dependent glucocorticoid-related complications and serious side effects. Therefore, in-depth studies investigating new solutions for the first-line treatment of ITP are urgently needed. Tacrolimus is a calcineurin inhibitor, which forms a complex by binding to FK506-binding protein. It is currently widely used in the prevention of graft-versus-host disease for organ transplantation as well as for the treatment of autoimmune diseases. In addition to recent retrospective studies and case reports demonstrating its effectiveness in ITP, tacrolimus has been shown to improve anti-platelet antibody-mediated thrombocytopenia in mice, suggesting it may be a potential treatment for ITP. The aim of this study was to compare two first-line treatment options for ITP-a standard glucocorticoid-only regimen versus tacrolimus in combination with a standard glucocorticoid regimen-to determine which could help patients achieve stable platelet counts faster and experience a longer duration of remission. Methods This open-label, randomized, phase 2 trial, enrolled adult ITP patients from seven different tertiary medical centers in China. Elderly patients had confirmed, newly diagnosed, treatment-naive ITP, platelet counts &lt;30×10 9/L, or &lt; 50×10 9/L and significant bleeding symptoms (World Health Organization bleeding scale ≥ 2). Eligible patients were randomly assigned 1:1 with an interactive web-based response system to receive either oral tacrolimus (initial 0.03 mg/kg/day and maintain blood concentration at 3-5 ng/mL for 12 weeks) plus high-dose dexamethasone (HD-DXM) or HD-DXM monotherapy for 12 weeks. DXM (40 mg) was administered orally daily for 4 consecutive days to both study arms. The 4-day course of DXM was repeated on days 11-14 in patients who lacked response by day 10. The primary endpoint was 6-month sustained response (SR), defined as platelet count maintained &gt;50×10 9/L without any additional ITP-modifying therapy at the 6-month follow-up. Key secondary endpoints included initial response by day 14 (OR, platelet count ≥30×10 9/L and at least 2-fold increase in baseline platelet count and absence of bleeding; and CR, platelet count ≥ 100×10 9/L), duration of response, bleeding scores, and adverse events (AEs). This trial was registered with ClinicalTrials.gov (NCT04747080). Results Total 140 patients newly diagnosed with ITP were randomly assigned to either the tacrolimus plus HD-DXM (n=72) or HD-DXM monotherapy (n=68) groups. At the 6-month follow-up, the proportion of patients exhibiting SR was significantly higher in the tacrolimus plus HD-DXM group than in the HD-DXM monotherapy group (65.3% vs 42.6%, p= 0.007). Of the 140 patients with ITP (males accounted for 48.6%), the mean age was 32.8 years, the mean platelet count was 16.7×10 9/L. The combination group exhibited a higher 14-day early remission rate than the monotherapy group (76.4% vs 55.9%, P=0.001). Significantly fewer treatment failures occurred in patients randomly assigned to the combination group(19.4% vs 38.2%, P=0.0014). During the follow-up period, fewer patients in the combination group experienced relapse than in the monotherapy group; the median time to relapse was 77 days (Tacrolimus+HD-DXM) vs 36 days (HD-DXM). The combination group exhibited a lower proportion of bleeding events and a lower bleeding score. The incidence of serious AEs, rescue therapy, and treatment side effects were similar between the two groups, and treatment was well tolerated by all patients, with no grade 4 AEs or treatment-related deaths reported. There was no statistically significant difference in the incidence of treatment-related AEs between the two groups. Conclusions Low-dose tacrolimus plus HD-DXM was an effective and safe treatment for ITP as first-line therapy and elicited a sustained prolonged response in adults. This therapy may be a new treatment option for adult patients with ITP. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: It includes information or discussion of off-label drug use of tacrilimus.

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