Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia

Blood ◽  
2010 ◽  
Vol 115 (14) ◽  
pp. 2755-2762 ◽  
Author(s):  
Francesco Zaja ◽  
Michele Baccarani ◽  
Patrizio Mazza ◽  
Monica Bocchia ◽  
Luigi Gugliotta ◽  
...  

Abstract Previous observational studies suggest that rituximab may be useful in the treatment of primary immune thrombocytopenia (ITP). This randomized trial investigated rituximab efficacy in previously untreated adult ITP patients with a platelet count of 20 × 109/L or less. One hundred three patients were randomly assigned to receive 40 mg/d dexamethasone for 4 days with or without 375 mg/m2 rituximab weekly for 4 weeks. Patients who were refractory to dexamethasone alone received salvage therapy with dexamethasone plus rituximab. Sustained response (ie, platelet count ≥ 50 × 109/L at month 6 after treatment initiation), evaluable in 101 patients, was greater in patients treated with dexamethasone plus rituximab (n = 49) than in those treated with dexamethasone alone (n = 52; 63% vs 36%, P = .004, 95% confidence interval [95% CI], 0.079-0.455). Patients in the experimental arm showed increased incidences of grade 3 to 4 adverse events (10% vs 2%, P = .082, 95% CI, −0.010 to 0.175), but incidences of serious adverse events were similar in both arms (6% vs 2%, P = .284, 95% CI, −0.035 to 0.119). Dexamethasone plus rituximab was an effective salvage therapy in 56% of patients refractory to dexamethasone. The combination of dexamethasone and rituximab improved platelet counts compared with dexamethasone alone. Thus, combination therapy may represent an effective treatment option before splenectomy. This study is registered at http://clinicaltrials.gov as NCT00770562.

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4907-4907
Author(s):  
Mohsen Saleh Elalfy ◽  
Tamer Hassan ◽  
Khalid Elsayh ◽  
Mohamed Maebid ◽  
Hoda Hassab ◽  
...  

Background: Primary immune thrombocytopenia (ITP) has been treated with steroids or immune-suppressive. Thrombopoietin receptor agonists (TPO-RAs), changed the treatment landscape for ITP. Romiplostim and Eltrombopag were FDA approved for use in pediatric patients ≥1 year with ITP of >6 months' duration and insufficient response to previous therapy. Following the guidelines is not always feasible in practice. Aim and Methodology Centers treating more than 25 new cases/year with good recording system were included; aiming to report outcome, adverse events (AEs) and deviation from guidelines. Newly diagnosed ITP children were excluded. Data was collected from January 2017- June 2019; children age >1 to 18 years with persistent ITP (3-<12 months) or chronic (≥12 months), who had previously been treated with ≥1 previous ITP therapy, and had platelet counts (PC) persistently <30×109/l with moderate-severe bleeding. Eltrombopag was described in a dose of 25 mg/day for those > 1 to 12 years; or in 50 mg/day for those >12-18 years; dose was escalated to 50 or 75mg/day for those 6-12 and >12 years respectively on failure to have PC > 50 x 109/L. Weekly CBC and self-record of bleeding for 1st 24 week then bi-weekly. Failure to show a good response; Eltrombopag dosing should be adjusted to achieve that goal and not to exceed 200 × 109/L. Romiplostim was used in 1 ug/kg and escalated up to 10 ug/kg according to response. Serious AEs were reported to ethical committee within 24 hours. Results Two years Observational study of 204 out of 1080 primary ITP (268 persistent and 812 chronic); 55% females median age 8 years, received Eltrombopag (n=186), Romiplostim (n= 18) from 3-30 months was prescribed after failure of 1-5 lines of therapy in 15% of Persistent ITP and 20% of chronic ITP. Adequate response at 24 weeks in 60% on Eltrombopag or Romiplostim had a significant reduction in both skin-related and non-skin-related bleeding symptoms). However 50% discontinued treatment; (40% due to inadequate response, 8% irregular availability and 2% due to SAEs). Deviation from guidelines in 40%; (15% started Eltrombopag early between 3-6 months who showed a higher response rate; half of them could stop it without drop of PC); while 20% continued Eltrombopag for >12 month with lack of response after dose escalation at 24th week and 5% were not following the described dose or the regular monitoring. 40% of chronic ITP patients achieved platelet counts of >50 x 109/L or more at least twice. Common adverse events included; headache (10%). myalgia (10%), rhinitis (8%), diarrhea 8% Serious adverse events occurred in 4 (1 elevated transaminases, one unrelated life-threatening bleeding and two high PC; >1000 x109/L). Conclusion: TPO-RAs were used in almost 15% of persistent and 20% of chronic ITP as 2nd line or more therapy and in 90% was Eltrombopag; which produced an excellent response for those 3-6 months; deviating from guidelines. It showed a sustained platelet response in 40% of patients with chronic ITP, however it should be stopped if showing poor response after dose escalation. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4196-4196 ◽  
Author(s):  
Maria Cristina Moragues Martinez ◽  
Kati Hurst ◽  
Maria Eva Mingot Castellano ◽  
Ana Isabel Heiniger Mazo

Abstract Introduction: Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by accelerated platelet destruction and inadequate platelet production mediated by autoantibodies. As there are no specific diagnostic tests, the diagnosis of ITP remains one of exclusion. Although the incidence of ITP increases with age, there are no practice guidelines for elderly patients and few studies have been conducted. Compared with younger patients, older patients have a higher incidence of serious bleeding complications and increased related mortality. Therefore we propose to describe our experience in the management of ITP in patients over 65 years old. Methods: We conducted a retrospective study of 44 patients over 65 years old at the moment of the ITP diagnosis, treated in our center from January 1995 to March 2014. Variables analyzed were age, Charlson score, clinical manifestations and platelet count at diagnosis, type of treatment, response to treatment and adverse events. Results: The median current age is 77 years (IQR, 70-84 years), with a median age at diagnosis of 69 years (IQR, 65-75 years). The ratio of males to females was 0.91. Eighteen (40.9%) patients had a Charlson score greater than or equal to 2. The comorbilities were 27.8% diabetes with damage to target organs; 11.4% coronary disease; 9.8% solid metastatic tumor, 9.8% peripheral vascular disease, 9.8% chronic pulmonary disease; 5% congestive heart failure, 5% peptic ulcer, 5% cerebrovascular disease, 5% moderate-severe liver disease, 5% moderate-severe renal disease y 1.6% connective tissue disease, 1.6% dementia, 1.6% hemiplegia and 1.6% leukemia. The mean platelet count at diagnosis was 28x109 / L (IQR, 8-74x109 / L). Initial presentation was thrombocytopenia on a routine blood count in 43% of patients while the rest presented bleeding symptoms. Fourteen patients (31.8%) required admission on diagnosis. 18.8% showed major bleeding: 6 (13.63%) gastrointestinal haemorrhages, 1 (2.2%) hematuria and 47.7% minor bleeding: 8 (18.18%) bruising, 7 (15.9%) mucosal bleeding and 7 (15.89%) purpura and epistaxis. Regarding treatment, observation was used in 11 patients (25%), all of whom subsequently acheived spontaneous remission. Corticosteroid therapy (prednisone 0.5-1mg/kg), was the initial treatment used in 13 patients (29.5%), 15.9% received intravenous inmunoglobulins (1gr/kg x 2 days) and 18.2% combination therapy. A response was obtained in 75.6% of patients (35.6% CR, 40% R). Seven (16%) subjects received second-line treatment (1 splenectomy, 3 romiplostim, 1 eltrombopag, 1 rituximab, 1 Imurel). The patient that underwent splenectomy obtained CR. Of the 3 patients treated with romiplostim, 2 achieved CR directly, and the third required rescue therapy with eltrombopag to reach CR. The patient that received second line treatment with eltrombopag obtained R and the patient treated with Rituximab failed and needed rescue therapy with romiplostim. Finally the patient treated with azathioprine is in CR but still on treatment. At present we have an 84.1% response rate after a median follow up of 66 months (IQR, 27-100 months). During treatment we observed a single vascular event in the form of deep vein thrombosis with associated pulmonary embolism in a subject with additional thromboembolic risk factors. We found no infections, hyperglycemia or hypertensive crisis which required hospital admission or special monitoring. Five patients (11.4%) developed neoplasms (hepatocellular carcinoma, rectal neoplasm, pancreatic adenocarcinoma and Hürthle cell carcinoma), none of which were haematological. Three patients died: 2 due to neoplasm progression and 1 to acute renal failure. Conclusions: Low and intermediate doses of corticosteroids are a good first line treatment option in elderly patients. Close monitoring of the patient is advisable to ensure the early detection and treatment of adverse events and possible underlying diseases that could justify the thrombocytopenia. In our series the incidence of major bleeding in over 65s with ITP is clearly superior to that reported in younger subjects. Therefore, it is essential to optimize the intensity and duration of treatment in these patients. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2012 ◽  
Vol 120 (18) ◽  
pp. 3670-3676 ◽  
Author(s):  
Tadeusz Robak ◽  
Jerzy Windyga ◽  
Jacek Trelinski ◽  
Mario von Depka Prondzinski ◽  
Aristoteles Giagounidis ◽  
...  

Abstract Rozrolimupab, a recombinant mixture of 25 fully human RhD-specific monoclonal antibodies, represents a new class of recombinant human antibody mixtures. In a phase 1 or 2 dose escalation study, RhD+ patients (61 subjects) with primary immune thrombocytopenia received a single intravenous dose of rozrolimupab ranging from 75 to 300 μg/kg. The primary outcome was the occurrence of adverse events. The principal secondary outcome was the effect on platelet levels 7 days after the treatment. The most common adverse events were headache and pyrexia, mostly mild, and reported in 20% and 13% of the patients, respectively, without dose relationship. Rozrolimupab caused an expected transient reduction of hemoglobin concentration in the majority of the patients. At the dose of 300 μg/kg platelet responses, defined as platelet count ≥ 30 × 109/L and an increase in platelet count by > 20 × 109/L from baseline were observed after 72 hours and persisted for at least 7 days in 8 of 13 patients (62%). Platelet responses were observed within 24 hours in 23% of patients and lasted for a median of 14 days. Rozrolimupab was well tolerated and elicited rapid platelet responses in patients with immune thrombocytopenia and may be a useful alternative to plasma-derived products. This trial is registered at www.clinicaltrials.gov as #NCT00718692.


2019 ◽  
Vol 14 (1) ◽  
pp. 31-36
Author(s):  
Raafat Abdel-Malek ◽  
Kyrillus S. Shohdy ◽  
Noha Abbas ◽  
Mohamed Ismail ◽  
Emad Hamada ◽  
...  

Background: Several single chemotherapeutic agents have been evaluated as the second-line treatment of advanced urothelial carcinoma. Despite encouraging efficacy outcomes, toxicity has often led to dose modifications or discontinuation. We aimed to assess the safety of vinflunine in a particular population of advanced transitional cell carcinoma of urothelium (TCCU), that were exposed to the previous toxicity of chemotherapy. Methods: This is an open-label, prospective, single-center pilot study to evaluate the response rate and safety profile of vinflunine in patients with advanced TCCU. It was planned to enroll 25 evaluable patients. Eligible patients are those with progressive disease after first-line platinum-based regimen for advanced or metastatic disease. Results: The study was prematurely closed due to two sudden deaths that were judged by the review board as treatment-related. Only ten patients were evaluated and received at least one cycle of vinflunine. All but one were male and seven underwent radical surgery. Eight had a distant metastasis (mainly lung and/or liver). Disease control rate was 40%, four patients had a partial response with median duration of response of 3.5 months. The median overall survival was 3.2 months (95% CI:1.67- 4.73). There were three serious adverse events namely two sudden deaths and one grade 4 thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all-grade adverse events were fatigue (50%), constipation (40%) and vomiting (40%). Moreover, grade 3 fatigue occurred in 30% of patients. Only one patient, who achieved PR for 5 months, was fit to receive further cytotoxic chemotherapy. Conclusion: The activity of vinflunine in advanced urothelial carcinoma came at the expense of its safety. The use of vinflunine has to be limited to the selected group of patients. However, this is a single institute experience in a limited number of patients.


2019 ◽  
pp. 331-340
Author(s):  
Susan Churchill ◽  
◽  
Kayla Deru ◽  
Lindell K. Weaver ◽  
Steffanie H. Wilson ◽  
...  

Safety monitoring and successful blinding are important features of randomized, blinded clinical trials. We report chamber- and protocol-related adverse events (AEs) for participants enrolled in two randomized, double-blind clinical trials of hyperbaric oxygen (HBO2) for persistent post-concussive symptoms clinicaltrials.gov identifiers NCT01306968, HOPPS, and NCT01611194, BIMA), as well as the success of maintaining the blind with a low-pressure sham control arm. In both studies, participants were randomized to receive HBO2 (1.5 atmospheres absolute, >99% oxygen) or sham chamber sessions (1.2 atmospheres absolute, room air). In 143 participants undergoing 4,245 chamber sessions, chamber-related adverse events were rare (1.1% in the HOPPS study, 2.2% in the BIMA study). Minor, non-limiting barotrauma was the most frequently reported. Rarely, some participants experienced headache with chamber sessions. No serious adverse events were associated with chamber sessions. An allocation questionnaire completed after intervention revealed that the sham control arm adequately protected the blind in both trials. Participants based allocation assumptions on symptom improvement or lack of symptom improvement and could not discern intervention arm by pressure, smell, taste, or gas flow.


2019 ◽  
Vol 33 ◽  
pp. 205873841987212 ◽  
Author(s):  
Xiaoling Cheng ◽  
Kuo Yan ◽  
Jingyao Ma ◽  
Zhenping Chen ◽  
Libo Zhao ◽  
...  

The treatment of severe chronic immune thrombocytopenia (SCITP) in pediatric patients is challenging. We evaluated the clinical efficacy and safety of eltrombopag in children with SCITP in China. This observational study was carried out at the Hematology Oncology Center, Beijing Children’s Hospital between April 2017 and July 2018. Patients with SCITP who had at least 12 weeks of eltrombopag treatment and follow-up data were included. Baseline data, such as age, drug dosage, pre-study platelet count, concomitant medications, and bleeding severity, were collected. Treatment response rates, durable response rates, bleeding events, and adverse events were assessed during eltrombopag therapy for at least 12 weeks. The median duration of eltrombopag therapy was 16 (12–48) weeks. The overall, complete, and partial response rates were 75% (15/20), 35% (7/20), and 40% (8/20), respectively. The durable response rate was 70% (14/20). No serious bleeding events or serious adverse events occurred during the study period. Eltrombopag appears to be effective and safe in children with SCITP, although additional research is needed to confirm this.


2020 ◽  
Vol 38 (10) ◽  
pp. 1006-1018 ◽  
Author(s):  
Kim-Hien T. Dao ◽  
Jason Gotlib ◽  
Michael M.N. Deininger ◽  
Stephen T. Oh ◽  
Jorge E. Cortes ◽  
...  

PURPOSE Colony-stimulating factor-3 receptor ( CSF3R)-T618I is a recurrent activating mutation in chronic neutrophilic leukemia (CNL) and to a lesser extent in atypical chronic myeloid leukemia (aCML) resulting in constitutive JAK-STAT signaling. We sought to evaluate safety and efficacy of the JAK1/2 inhibitor ruxolitinib in patients with CNL and aCML, irrespective of CSF3R mutation status. METHODS We conducted a phase II study of ruxolitinib in 44 patients (21 CNL and 23 aCML). The primary end point was overall hematologic response rate (ORR) by the end of 6 continuous 28-day cycles for the first 25 patients enrolled. We considered a response as either partial (PR) or complete response (CR). We expanded accrual to 44 patients to increase our ability to evaluate secondary end points, including grade ≥ 3 adverse events, spleen volume, symptom assessment, genetic correlates of response, and 2-year survival. RESULTS ORR was 32% for the first 25 enrolled patients (8 PR [7 CNL and 1 aCML]). In the larger cohort of 44 patients, 35% had a response (11 PR [9 CNL and 2 aCML] and 4 CR [CNL]), and 50% had oncogenic CSF3R mutations. The mean absolute allele burden reduction of CSF3R-T618I after 6 cycles was greatest in the CR group, compared with the PR and no response groups. The most common cause of death is due to disease progression. Grade ≥ 3 anemia and thrombocytopenia were observed in 34% and 14% of patients, respectively. No serious adverse events attributed to ruxolitinib were observed. CONCLUSION Ruxolitinib was well tolerated and demonstrated an estimated response rate of 32%. Patients with a diagnosis of CNL and/or harboring CSF3R-T618I were most likely to respond.


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