scholarly journals Eltrombopag in adult patients with immune thrombocytopenia in the real‐world in France, including off‐label use before 6 months of disease duration. The multicenter, prospective ELEXTRA study

2021 ◽  
Author(s):  
Guillaume Moulis ◽  
Johanne Germain ◽  
Manuela Rueter ◽  
Margaux Lafaurie ◽  
Myriam Aroichane ◽  
...  
Keyword(s):  
Real World ◽  
Immune Thrombocytopenia ◽  
Disease Duration ◽  
Adult Patients ◽  
Off Label Use ◽  
The Real ◽  
Off Label ◽  
Label Use

Real‐world off‐label use of icatibant for acute management of non‐hereditary angioedema

2021 ◽  
Vol 51 (3) ◽  
pp. 419-423
Author(s):  
Thanh‐Thao (Adriana) Le ◽  
William Smith ◽  
Pravin Hissaria
Keyword(s):  
Real World ◽  
Hereditary Angioedema ◽  
Acute Management ◽  
Off Label Use ◽  
Off Label ◽  
Label Use

ATG Dose Correlates with Acute and Chronic GvHD In Patients Undergoing Reduced-Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation: A Large Retrospective Monocenter Analysis on 301 Patients.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3485-3485
Author(s):  
Roberto Crocchiolo ◽  
Sabine Furst ◽  
Luca Castagna ◽  
Jean El Cheikh ◽  
Catherine Faucher ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Adult Patients ◽  
Off Label Use ◽  
Off Label ◽  
Grade 3 ◽  
Label Use

Abstract Abstract 3485 Introduction: RIC associating Fludarabine-Busulfan-ATG (FBA) is quite popular as preparative for allogeneic hematopoietic stem cell transplantation (RIC-AlloSCT). However the best association us still a matter of debate. Busulfan is crucial for disease control but limited by a dose-dependent toxicity and ATG plays a pivotal role in the prevention of both acute and chronic GvHD but with a potential higher relapse rate. Here we retrospectively compared different FBA regimens among adult patients transplanted at our Institution for a hematological malignancy, with the aim of identifying whether some pre- or peri-transplant variables are predictive of outcome. Patients and methods: on 635 patients allografted between May 1998 and Feb 2010, a total of 301 patients affected by malignancy received FBA-based RIC-AlloSCT and were the object of the present analysis. Comparisons between baseline patient, donor and AlloSCT characteristics with transplant outcome were performed: univariate and multivariate Cox regression analysis were used to find any correlation between the above mentioned variables and OS, DFS, NRM, relapse incidence, acute (aGvHD) and chronic (cGvHD) GvHD. Variables with p<0.20 were included in multivariate analysis, and only variables with a p<0.05 were retained in the final model. Results: median (range) follow-up was 917 (71-4051) days. Two-year OS, DFS and NRM were 66%, 58% and 20% for the entire cohort. Relapse at two years was 26%. Cumulative incidence of grade 2–4, grade 3–4, overall and extensive cGvHD were: 29%, 12%, 58% and 40%. In multivariate analysis, patient's age was significantly associated with OS, NRM, grade 2–4 and 3–4 aGvHD; disease status at transplant significantly correlated with DFS and relapse incidence. ATG at a dose of 5 mg/kg compared to 2.5 mg/kg, was significantly associated with a reduced risk of developing grade 3–4 aGvHD (HR= 0.46, 95% CI: 0.22–0.99, p=0.05) and cGvHD (HR= 0.33, 95% CI: 0.20–0.54, p<0.0001), without affecting relapse (p=n.s.). Overtime we modified our standard RIC from F5B2A1 (Fludarabine over 5 d, oral Bu over 2 d and ATG for1d) (N=114) to F5BX2A2 (Fludarabine over 5 d, IV Bu over 2 d and ATG over 2 d) (N=84). Population was not similar and notably older (51 vs. 57 years, p<0.0001) in the latter group. Despite this we observed similar NRM (22% vs. 23%: p=n.s.) in patients older than 55 years; in patients younger than 55 F5BX2A2 was associated with better but not statistically significant OS (77% vs. 65% at two years, p=0.21) and reduced NRM (9% vs. 18% at two years, p=0.10). Conclusions: in this large monocenter series of adult patients undergoing FBA-based RIC-AlloSCT, the use of ATG at a dose of 5 mg/kg appeared to significantly reduce incidence and severity of cGvHD and grade 3–4 aGvHD compared to ATG 2.5 mg/kg without increasing disease relapse. Moreover, despite patients' disparity between the two cohorts, reduced NRM was observed in patients < 55 years old treated with F5BX2A2 regimen with respect to those receiving F5B2A1. Disclosures: Off Label Use: Zevalin is off-label use in conditioning regimen in France.

Prognostic Impact of CD20 and CD25 Expression in Patients with Philadelphia-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 984-984 ◽  
Author(s):  
Fabio P.S. Santos ◽  
Susan O'Brien ◽  
Deborah A. Thomas ◽  
Jorge Cortes ◽  
Stefan Faderl ◽  
...  
Keyword(s):  
Research Funding ◽  
Adult Patients ◽  
Lower Percentage ◽  
Prognostic Impact ◽  
Off Label Use ◽  
Conventional Chemotherapy ◽  
Off Label ◽  
Cd25 Expression ◽  
Significant Difference ◽  
Label Use

Abstract Abstract 984 Poster Board I-6 Background: The Ph chromosome is the most common cytogenetic abnormality in adult patients with ALL and is associated with a higher risk of relapse and death. With the introduction of tyrosine kinase inhibitors (TKI; imatinib, dasatinib), the treatment of patients with Ph+ ALL has evolved. Regimens combining conventional chemotherapy with TKI have lead to significant improvements in the outcome of these patients. However, there is still a high incidence of relapse, and the determination of prognostic factors in these patients might lead to the development of risk-adapted therapy. CD20 is a cell surface marker expressed in 40% of adult patients with ALL, and it is associated with worse survival (Thomas D et al, Blood 2009; 113: 6330-6337). CD25 is the a-chain of the IL-2 receptor and has been reported to be associated with adverse outcomes in Ph+ ALL (Paietta E et al, Blood 2008; 112:Abstract 1500). Aims: To determine the prognostic impact of CD20 and CD25 expression in patients with Ph+ ALL. Methods: We retrospectively reviewed data of patients with Ph+ ALL treated at our institution with conventional chemotherapeutic protocols (Hyper-CVAD) alone or combined with TKI (Hyper-CVAD + imatinib and Hyper-CVAD + dasatinib). None of the patients received therapy with Rituximab. CD20 and CD25 expression were assessed by flow cytometry, and the cut-off for positivity was 20%. Survival was estimated by Kaplan-Meier method and compared by log-rank test. Results: We analyzed 126 patients with Ph+-ALL treated at our institution from November, 1992, until February, 2009. Patients received Hyper-CVAD alone (N=44), Hyper-CVAD + Imatinib (N=47) and Hyper-CVAD + Dasatinib (N=35). Median age of the whole cohort was 49 years (range 16-84). CD20 was positive in 69 of 124 (57%) evaluable patients. CD25 was positive in 63 of 112 (56%) evaluable patients. Patients that were CD20-positive had a higher incidence of peripheral lymphadenopathy (21% vs. 7%, p=0.04). Patients that were CD25-positive had lower lactate dehydrogenase (LDH) levels (median 1006 IU/L vs. 1433 IU/L; p=0.01), lower percentage of bone marrow blasts (median 86% vs. 90%, p=0.02), higher platelet counts (median 50×109/L vs. 32×109/L, p=0.01) and a higher incidence of CNS disease at diagnosis (21% vs. 4%, p=0.01). The complete response rate of the whole cohort was 91%. There was no impact of CD20 or CD25 positivity on disease-free survival (DFS) and overall survival (OS) of patients treated with Hyper-CVAD alone. In patients treated with Hyper-CVAD + dasatinib, CD20 positivity was associated with improved DFS (Figure 1) (median – not reached [NR] vs. 48 weeks [wks], p=0.01) and OS (median NR vs. 65 wks, p=0.06). Patients treated with Hyper-CVAD + imatinib who were CD20-positive had better DFS (median 91 vs. 57 wks, p=0.77) and OS (median 118 vs. 73 wks, p=0.98), but this did not reach statistical significance. There was a trend for worse survival in patients treated with Hyper-CVAD + dasatinib that were CD25 positive, but without a statistically significant difference (median DFS 55 wks vs. NR, p=0.10; median OS 85 wks vs. NR, p=0.11). We repeated the analysis combining Hyper-CVAD + dasatinib and Hyper-CVAD + imatinib (Hyper-CVAD + TKI). There was no significant difference in DFS and OS by CD20 expression (median DFS 130 wks vs. 53 wks, p=0.11; median OS 124 wks vs. 74 wks, p=0.11) or CD25 expression (median DFS 63 wks vs. 86 wks, p=0.33; median OS 100 wks vs. 117 wks, p=0.39). Conclusion: In patients with Ph+-ALL treated with regimens combining conventional chemotherapy and TKI, expression of CD20 may be associated with better survival outcomes. CD25 did not influence survival in our patients. More studies are needed to better determine the prognostic value of these markers and implement risk-adapted strategies treatment. Disclosures: Off Label Use: Off label use of imatinib and dasatinib in combination with cytotoxic chemotherapy. Cortes:Novartis: Research Funding; Bristol Myers Squibb: Research Funding. Kantarjian:Novartis: Research Funding; Bristol Myers Squibb: Research Funding.

Are Risk Evaluation and Mitigation Strategies Associated With Less Off-Label Use of Medications? The Case of Immune Thrombocytopenia

2014 ◽  
Vol 97 (2) ◽  
pp. 186-193 ◽  
Author(s):  
A Sarpatwari ◽  
JM Franklin ◽  
J Avorn ◽  
JD Seeger ◽  
JE Landon ◽  
...  
Keyword(s):  
Risk Evaluation ◽  
Immune Thrombocytopenia ◽  
Mitigation Strategies ◽  
Off Label Use ◽  
Off Label ◽  
Label Use

scholarly journals Phase 1/2 Study in Pediatric Patients with Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) Receiving Blinatumomab Treatment

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2292-2292 ◽  
Author(s):  
Arend von Stackelberg ◽  
Franco Locatelli ◽  
Gerhard Zugmaier ◽  
Rupert Handgretinger ◽  
Tanya M. Trippett ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Pediatric Patients ◽  
Phase 1 ◽  
Adult Patients ◽  
Off Label Use ◽  
Employment Equity ◽  
Hematopoietic Stem ◽  
Off Label ◽  
Equity Ownership ◽  
Label Use

Abstract Introduction: Blinatumomab, an investigational bispecific T-cell engager (BiTE®) antibody construct, has been shown to induce remission in adult patients with relapsed/refractory BCP-ALL. Medically important adverse events (AEs) related to blinatumomab treatment in adults are cytokine release syndrome (CRS) and neurological events. We report the primary analysis of the phase 1 portion of a multicenter phase 1/2 study of blinatumomab in pediatric patients with relapsed/refractory BCP-ALL. Methods: In this continuing study, eligible patients are <18 years old and must have BCP-ALL that is in second or later bone marrow relapse, in any marrow relapse after allogeneic hematopoietic stem cell transplantation (HSCT), or refractory to induction or reinduction therapy. Patients receive blinatumomab for 28 days by continuous intravenous infusion followed by a 14-day treatment-free period (for up to five cycles). Escalating dosing levels of 5, 15, and 30 μg/m²/day and stepwise dosing of 5–15 or 15–30 μg/m²/day were evaluated. The primary endpoint of the phase 1 portion of the study was maximum tolerated dose (MTD). Secondary endpoints included toxicity, complete remission (CR) rate, overall survival (OS), relapse-free survival (RFS), pharmacokinetics evaluation, and cytokine measurement. Results: In the phase 1 portion, 41 patients received a total of 73 cycles (median of 2 cycles received, range of 1 to 5). Eight (20%) patients had refractory disease and seven (17%) had experienced at least two bone marrow relapses. Twenty-six (63%) patients had relapsed following HSCT. Dose-limiting toxicities (DLTs) are listed in Table 1. The MTD was established at 15 µg/m²/day. To decrease the risk of CRS, a stepwise dose of 5–15 μg/m²/day was recommended for the phase 2 part of the study (5 µg/m²/day for 7 days, then 15 µg/m²/day). This dose was subsequently assessed in two age groups (2–6 and 7–17 years) in the phase 1 expansion part with one of 18 patients developing grade 3 CRS. No patient in the expansion cohort developed grade 4 or 5 CRS. Across all dosing levels, 13 (32%) patients had CR with 10 (77%) achieving minimal residual disease (MRD) negativity. Of these 13 patients, nine (69%) underwent HSCT. Among patients who achieved CR, median RFS was 8.3 months (95% CI: 3.0–16.0 months). Median OS was 5.7 months (95% CI: 3.3–9.7 months; Figure 1) with a median follow-up time of 12.4 months. Across all dosing levels, the most common AEs regardless of causality were pyrexia (78%), headache (37%), hypertension (32%), nausea (29%), abdominal pain (27%), pain in the extremity (27%), and anemia (27%). Pharmacokinetic parameters, including steady-state concentration (Css), clearance, and half-life were similar to those from adult patients with relapsed/refractory BCP-ALL who received body surface area-based blinatumomab dosing. Transient elevations of serum cytokines were observed mostly within the first two days after starting blinatumomab, in particular IL-6, IFN-gamma, IL-10, and, to a lesser extent, IL-2 and TNF-α. Conclusions: In the phase 1 portion of this study in pediatric patients with relapsed/refractory BCP-ALL, the MTD was 15 µg/m²/day. CRS was dose-limiting, but stepwise dosing of 5–15 μg/m²/day has been effective in ameliorating CRS. Thirty-two percent of patients achieved CR and more than half were able to proceed to allogeneic HSCT. Figure 1 Figure 1. Disclosures von Stackelberg: Amgen: Consultancy, Honoraria. Off Label Use: This presentation will discuss the off-label use of blinatumomab, as this agent is not approved for use by the FDA, EMA or any other regulatory authorities.. Zugmaier:Amgen Inc.: Equity Ownership; Amgen Research (Munich) GmbH: Employment. Rheingold:Novartis: Consultancy. Hu:Amgen Inc.: Employment, Equity Ownership. Mergen:Amgen Inc.: Equity Ownership; Amgen Research (Munich) GmbH: Employment. Fischer:Amgen Inc.: Equity Ownership; Amgen Research (Munich) GmbH: Employment. Zhu:Amgen Inc.: Employment, Equity Ownership. Hijazi:Amgen Inc.: Equity Ownership; Amgen Research (Munich) GmbH: Employment. Gore:Amgen Inc.: Travel Support Other.

scholarly journals Real-world Inpatient Use of Medications Repurposed for COVID-19 in U.S. Hospitals, March-May 2020

2020 ◽  
Author(s):  
Sameer S Kadri ◽  
Cumhur Y Demirkale ◽  
Junfeng Sun ◽  
Lindsay M Busch ◽  
Jeffrey R Strich ◽  
...  
Keyword(s):  
Real World ◽  
Off Label Use ◽  
Mechanically Ventilated ◽  
Off Label ◽  
Use Patterns ◽  
Label Use

Abstract We report off-label use patterns for medications repurposed for COVID-19 at 318 U.S. hospitals. Inpatient hydroxychloroquine use declined by 80%, while corticosteroids and tocilizumab were initiated two days earlier in May versus March 2020. Two-thirds of ventilated COVID-19 patients were already receiving corticosteroids during March-May, resembling pre-COVID use in mechanically ventilated influenza patients.

scholarly journals Off-label use of intravenous thrombolysis for acute ischemic stroke: a critical appraisal of randomized and real-world evidence

2021 ◽  
Vol 14 ◽  
pp. 175628642199736
Author(s):  
Georgios Tsivgoulis ◽  
Odysseas Kargiotis ◽  
Gianmarco De Marchis ◽  
Martin Kohrmann ◽  
Else Charlotte Sandset ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Real World ◽  
Intravenous Thrombolysis ◽  
Therapeutic Window ◽  
Off Label Use ◽  
Exclusion Criteria ◽  
Off Label ◽  
Thrombolytic Agents ◽  
Label Use

Intravenous thrombolysis (IVT) represents the only systemic reperfusion therapy able to reverse neurological deficit in patients with acute ischemic stroke (AIS). Despite its effectiveness in patients with or without large vessel occlusion, it can be offered only to a minority of them, because of the short therapeutic window and additional contraindications derived from stringent but arbitrary inclusion and exclusion criteria used in landmark randomized controlled clinical trials. Many absolute or relative contraindications lead to disparities between the official drug label and guidelines or expert recommendations. Based on recent advances in neuroimaging and evidence from cohort studies, off-label use of IVT is increasingly incorporated into the daily practice of many stroke centers. They relate to extension of therapeutic time windows, and expansion of indications in co-existing conditions originally listed in exclusion criteria, such as use of alternative thrombolytic agents, pre-treatment with antiplatelets, anticoagulants or low molecular weight heparins. In this narrative review, we summarize recent randomized and real-world data on the safety and efficacy of off-label use of IVT for AIS. We also make some practical recommendations to stroke physicians regarding the off-label use of thrombolytic agents in complex and uncommon presentations of AIS or other conditions mimicking acute cerebral ischemia. Finally, we provide guidance on the risks and benefits of IVT in numerous AIS subgroups, where equipoise exists and guidelines and treatment practices vary.

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