scholarly journals Off-Label Utilization Trend for Recombinant Factor VIIa in Children's Hospitals in the United States

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2177-2177
Author(s):  
Shveta Gupta ◽  
Joseph R. Stanek ◽  
Sarah H. O'Brien
Keyword(s):  
Mortality Rate ◽  
Board Of Directors ◽  
The United States ◽  
Factor Vii ◽  
Off Label Use ◽  
Advisory Committees ◽  
Diverse Range ◽  
Off Label ◽  
Factor Vii Deficiency ◽  
Label Use

Background: Recombinant FVIIa (rFVIIa) was approved by the Food and Drug Administration (FDA) as a hemostatic agent in 1999 for the treatment of patients with hemophilia and inhibitory antibodies against either factor VIII or IX and subsequently approved for use in patients with congenital factor VII deficiency and Glanzmann Thrombasthenia refractory to platelet transfusions in 2005 and 2014 respectively. These are rare disorders and the use of rFVIIa in these conditions has been found to be effective and safe. Despite this very narrow indication for usage, rFVIIa is being used for a diverse range of off-label indications. Along with uncertainty regarding clinical efficacy, available data suggests that the risk of thromboembolic events is increased when rFVIIa is used in off-label settings. Studies on the off-label use of rFVIIa in children are limited to a few large case series. In a retrospective multicenter cohort study utilizing the Pediatric Health Information System (PHIS) administrative database, Witmer et al demonstrated a 10-fold increase in the annual rate of off-label admissions from 2000 to 2007. The mortality rate in the off-label group was 34% and thrombotic events occurred in 11% of the off-label admissions. We conducted a follow up study to characterize the evolution of the off-label use of rFVIIa in children. Objective: To describe current trends of off-label utilization and adverse effects of rFVIIa in children. Study design: A retrospective multicenter cohort study utilizing the PHIS administrative database was conducted. The PHIS dataset includes 51 children's hospitals in the United States and is representative of tertiary care centers in the nation. In patients, 18 years of age or younger who received rFVIIa between 2012-2018 were included. A label admission was defined as an admission with an International Classification of Diseases (ICD-9 and ICD-10) diagnostic code for hemophilia, Factor VII deficiency or Glanzmann thrombaesthenia; admissions without these codes were classified as off-label. Data were analyzed descriptively. Results: There were 7,738 number of admissions, representing 6,493 unique individual subjects. A total of 78.3 % of the admissions were off-label. The rate of off-label use was stable at approximately 80% of the admissions from 2012-18. The most frequent admitting services for the off-label admissions included cardiology (29.8%), cardiovascular/thoracic surgery (15.7%), critical care (15.0%), neonatal-perinatal medicine (8.7%), and hematology/oncology (6.1%). Over half (54.6%) of off-label administration occurred in children younger than 1 year old. Among the off-label admissions 57 % were male and the median days of use of rFVIIa was 1 day. The mortality rate in the off-label group was 22.3 %. Thrombotic events occurred in 11.4% of the off-label admissions. Among the off-label admissions with thrombotic events, the most common admitting services were cardiology (35.0%) and critical care (21.2%). Conclusion: We have demonstrated that on a per admission basis the predominant use of rFVIIa is off-label. Thrombotic events are common. Although the mortality rate in the pediatric patients who received off-label rFVIIa is high; its lower when compared with the previous review. This may likely reflect, in part, the severity of illness in this patient group. In the absence of clearly supportive data demonstrating safety and efficacy, restraint should be exercised with careful consideration of risk versus benefit for use of rFVIIa in off-label settings. Disclosures Gupta: Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Research Funding; Takeda-Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. O'Brien:Pfizer: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding. OffLabel Disclosure: Recombinant FVIIa (rFVIIa) was approved by the Food and Drug Administration (FDA) as a hemostatic agent in 1999 for the treatment of patients with hemophilia and inhibitory antibodies against either factor VIII or IX and subsequently approved for use in patients with congenital factor VII deficiency and Glanzmann Thrombasthenia refractory to platelet transfusions in 2005 and 2014 respectively. These are rare disorders and the use of rFVIIa in these conditions has been found to be effective and safe. Despite this very narrow indication for usage, rFVIIa is being used for a diverse range of off-label indications.

Subcutaneous Alemtuzumab Combined with Oral Dexamethasone, Followed by Alemtuzumab Maintenance or Allo-SCT In CLL with 17p- or Refractory to Fludarabine – Interim Analysis of the CLL2O Trial of the GCLLSG and FCGCLL/MW

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 920-920 ◽  
Author(s):  
Stephan Stilgenbauer ◽  
Florence Cymbalista ◽  
Véronique Leblond ◽  
Alain Delmer ◽  
Thorsten Zenz ◽  
...  
Keyword(s):  
Disease Progression ◽  
Board Of Directors ◽  
Research Funding ◽  
Remission Rate ◽  
High Dose ◽  
Off Label Use ◽  
Advisory Committees ◽  
Off Label ◽  
Oral Dexamethasone ◽  
Label Use

Abstract Abstract 920 CLL refractory to purine analogues (e.g. fludarabine, F) or with 17p- is associated with very poor prognosis. Alemtuzumab is active in F-refractory CLL, and has proven efficacy in patients (pts) with 17p-. However, outcome of F-refractory CLL is still poor in terms of remission rate and duration of remission. The multinational, multicenter CLL2O trial aims at achieving a higher remission rate by adding high-dose dexamethasone to alemtuzumab, and prolongation of remission duration and survival by alemtuzumab maintenance or allogeneic stem-cell transplantation (allo-SCT). Pts with CLL refractory (no PR/CR or PR/CR < 6 months) to F-based (e.g. FR, FC, FCR) or similar chemotherapy (i.e. pentostatin, cladribine, bendamustine), or exhibiting 17p- (untreated or at relapse) were eligible if they had “active disease”. Treatment was with subcutaneous alemtuzumab 30 mg weekly × 3 for 28 days, combined with oral dexamethasone 40 mg on days 1–4 and 15–18, and prophylactic pegfilgrastim 6 mg days 1 and 15. Depending on the remission status, pts were treated for up to 12 weeks. If CR was documented at 4 or 8 weeks, or at least SD was achieved at 12 weeks, consolidation was scheduled with either allo-SCT or alemtuzumab maintenance with 30mg weekly every 14 days for up to 2 years (yrs). Decision for one of the two consolidation options was at discretion of patient and physician. From January 2008 to July 2010, 80 pts were enrolled at 22 centers and 79 were eligible; F-refractory (n=31), 17p- without prior therapy (n=31), and 17p- in relapse (n=17). Median age was 65 yrs in the F-refractory (range 38–76) and 17p- 1st-line group (36-76), and 60 yrs for the 17p- relapse group (54-73) with male predominance (F-refractory 74%, 17p- 1st-line 71%, 17p- relapse 82%). In the 17p- 1st-line and relapse groups, 52% and 50% were stage Binet C and exhibit reduced performance status (ECOG 1–2), compared to 81% Binet C and 60% ECOG 1–2 for the F-refractory cohort. Pretreated pts had received a median of 2 prior lines (F-refractory 1–6; 17p- relapse 1–5), and 5 pts had received prior SCT. In the F-refractory group, 16% of pts had 11q- and 52% had 17p-. IGHV was unmutated in 64% of 17p- groups and 72% in the F-refractory group. The median levels of ß2-MG / TK were 4.35 / 35.40 in the 17p- groups and 4.12 / 22.65 in the F-refractory group. Treatment data are currently available for 50 pts who completed induction therapy; F-refractory (n=19),17p- 1st-line (n=22), 17p- relapse (n=9). Full treatment duration (12 weeks) could be achieved in 47% F-refractory, 67% 17p- relapsed and 82% 17p- 1st-line pts. In the latter cohort, early stop of therapy was mainly correlated with CR, while in the F-refractory cohort with disease progression (n=2) and infections (n=5, 4 with no documented response). Response rates (ORR / CR) were 47% / 0% in the F-refractory cohort, 78% / 0% in the 17p- relapsed, and 100% / 23% in the 17p- 1st-line cohorts (as compared to this, ORR / CR was 71.4% / 4.8% with FCR in the 17p- 1st-line group of CLL8). Adverse events during treatment were mostly grade 1/2 apart from hematotoxicity. Grade 3/4 non-CMV infection occurred in 35% of F-refractory, 12% of 17p- relapsed, and 16% of 17p- 1st-line pts. CMV reactivation was observed in 32 % of the 17p- 1st-line pts, and less for the pretreated groups (F-refractory 16%, 17p- relapsed 18%). All CMV episodes were successfully treated, and there was no CMV-related death. Among 18 pts documented to receive alemtuzumab maintenance treatment, so far 3 SAEs have been reported: ITP (n=1, twice in the same pt), and fever / diarrhea / thyroiditis (n=1). At a median follow-up of 41.9 weeks (maintenance 54.7 weeks, allo-SCT 29 weeks), there were 7 (37%) deaths in the in the F-refractory cohort, 2 due to disease progression, and 5 due to infection. For the 17p- relapsed group, 3 progressions and 3 deaths were reported, with one case in each treatment option (SCT/maintenance), and one pt in salvage therapy. In the 17p- 1st-line cohort, 4 progressions occurred, 2 pts died, both in maintenance therapy. At 12 months, estimated overall survival was 54%, 66% and 100% in the F-refractory, 17p- relapse, and 17p- 1st-line cohorts, respectively. Accrual is currently ongoing with a target enrolment of 122 pts and updated results will be presented at the meeting. Disclosures: Stilgenbauer: Amgen: Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Sanofi Aventis: Research Funding. Off Label Use: off-label use of diagnostic tests and therapeutic agents. Leblond:ROCHE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MUNDIPHARMA : Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELGENE: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zenz:Roche: Honoraria; Boehringer: Honoraria; GSK: Honoraria; Celgene: Honoraria. Choquet:ROCHE : Consultancy. Hallek:Roche: Honoraria, Research Funding. Döhner:Pfizer: Research Funding.

Clinical Outcomes of Off-Label Use of Recombinant Activated Factor VII (rFVIIa) at Teaching Hospitals Affiliated with a Medical School.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4033-4033
Author(s):  
Yijun Cheng ◽  
Melissa S. Baxter ◽  
Walter S. Schroeder ◽  
Zale P. Bernstein
Keyword(s):  
Coagulation Factor ◽  
The United States ◽  
Factor Vii ◽  
Teaching Hospitals ◽  
Severe Bleeding ◽  
Consecutive Series ◽  
Off Label Use ◽  
Off Label ◽  
Prophylactic Use ◽  
Label Use

Abstract BACKGROUND: Recombinant factor VIIa (rFVIIa), NovoSeven®, is currently licensed in the United States for treatment of bleeding in hemophilia patients with acquired coagulation factor inhibitors. The off-label uses of this medication have expanded dramatically in past few years. Here we report our experience with the off-label use of rFVIIa at University at Buffalo affiliated teaching hospitals which include a level III trauma and major cardiothoracic centers. PATIENTS AND METHODS: We reviewed the clinical, laboratory, and radiographic data of a consecutive series of 43 patients who received off-label rFVIIa between December 2001 and September 2005. RESULTS: The indications for off-label rFVIIa use included CNS bleeding (17 patients), cardiothoracic and vascular surgery (9 patients), trauma (7 patients), GI bleeding (4 patients), coagulopathy (2 patients) and prophylaxis for surgery (4 patients). The dosage ranged from 32 to 150 mcg/kg with most patients receiving 90 mcg/kg. While a majority of patients received a single dose of rFVIIa (29 patients), one received a total of 22 doses. Overall 21 patients (49%) were alive at discharge. Those patients who received rFVIIa to stop severe bleeding from trauma or surgery appeared to have the worst outcome. The patient who received 22 doses of rFVIIa appeared to derive some clinical benefit after his initial doses, but became non-responsive to additional therapies. Successful hemostasis with rFVIIa was achieved in 100% of patients with preoperative prophylactic use. There were no thromboembolic events attributed to rFVIIa treatment. CONCLUSIONS: The outcome of off-label use of rFVIIa appears to correlate with clinical indications, with prophylactic use having greatest benefit and surgical hemorrhage, the worst. Our findings were used to revise guidelines to allow for more efficacious use of off-label rFVIIa.

Updated Results of a Phase 1/2a, Dose Escalation Study of Pvx-410 Multi-Peptide Cancer Vaccine in Patients with Smoldering Multiple Myeloma (SMM)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4246-4246 ◽  
Author(s):  
Ajay K. Nooka ◽  
Michael Wang ◽  
Andrew J. Yee ◽  
Sheeba K. Thomas ◽  
Elizabeth K. O'Donnell ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Immune Response ◽  
Board Of Directors ◽  
Research Funding ◽  
Post Treatment ◽  
Off Label Use ◽  
Advisory Committees ◽  
Off Label ◽  
Label Use

Methods: As reported previously, PVX-410 Multi-Peptide Vaccine (OncoPep, Inc.) is being developed for the treatment of SMM. PVX-410 consists of 4 human leukocyte antigen-A2 (HLA-A2), synthetic 9-mer peptides from unique regions of 3 multiple myeloma (MM)-associated antigens (XBP1 US184-192; XBP1 SP367-375; CD138260-268; and CS1239-247) emulsified in Montanide® ISA-720 VG (Seppic). Adults with SMM at high risk of progression to active MM and were HLA-A2-positive were eligible. The primary objective of this study was to determine the tolerability of PVX-410, initially as monotherapy. Immune response and change in M protein and free light chain ratio (FLC) were also assessed. PVX-410 alone was safe and immunogenic in the initial 12 patients treated, with all 12 having positive immune response to at least 1peptide, as determined by interferon-gamma enzyme-linked immunosorbent spot (Elispot) and tetramer assays. Given its immunomodulatory properties, it was hypothesized that co-administration of lenalidomide (len; Celgene Corporation) would enhance the T cell-mediated immune response induced by PVX-410. Accordingly, the tolerability, immunogenicity, and anti-MM activity of PVX-410+len was then investigated. Results in the PVX-410 alone cohort were previously reported. In the PVX-410+len cohort, patients received a dose of PVX-410, 0.8mg (0.2mg/peptide / 0.8mg total dose) subcutaneously plus 0.5 mL (1mg) Hiltonol® (poly-ICLC; Oncovir, Inc.) intramuscularly every 2 weeks for a total of 6 doses with 3 standard cycles of len (25 mg orally) on Days 1-21 every 28 days, without dexamethasone. Patients are followed for 12months post-treatment. Blood samples for immune response evaluation are collected at Week 0 (Baseline; pre-dose), 2, 4, and 8 during treatment and at Months 1, 3, 6, 9, and 12 post-treatment. Disease response is assessed at the same time points, except Weeks 0 and 2, using International Myeloma Working Group and modified European Group for Blood and Bone Marrow Transplant criteria. Results: Overall, 22 patients have been enrolled, with ages ranging from 39 to 82 years. Ten patients were enrolled in the PVX-410+len cohort, with 9 evaluable for response. All 10 patients received at least 1 cycle of len; 8 received all 3 cycles; 1 received 1 cycle before discontinuing due to a deviation; and 1 completed 2 cycles as of the cutoff date. One patient had 7 of 21 planned doses held due to neutropenia related to lenalidomide, but resumed the next cycle at a reduced dose (from 25 mg to 20 mg). Immunogenicity data with PVX-410+len and PVX-410 alone, as determined via intracellular cytokine staining and tetramer analysis, will be presented. With PVX-410 alone, 5 patients, 2 of 3 with the low-dose of 0.4 mg (0.1mg/peptide) and 3 of 9 at the target-dose (0.2 mg/peptide), experienced progression to active disease within 9 months post-treatment, and 7 had stable disease (SD) at the last follow up visit in the 12 month follow up period. With PVX-410+len, 5 patients have experienced partial or minimal responses and 3 have experienced SD. Durability of response is assessed through the 12-month study period; 1 patient has progressed to active myeloma during this time. PVX-410 was well-tolerated alone and with len. Most adverse events (AEs) have been ≤Grade 2 and non-serious. AEs seen more frequently with PVX-410+len versus PVX-410 alone are expected with len and include hematologic abnormalities (neutropenia, anemia, thrombocytopenia), gastrointestinal disorders (nausea, diarrhea, constipation), skin and cutaneous disorders (rash, pruritus), and myalgia. There was 1serious AE in the combination cohort (pneumonia), considered possibly related to len and unrelated to PVX-410. Conclusions: Six doses of PVX-410 were well tolerated in 22 patients with SMM. Additional AEs seen with PVX-410+len versus PVX-410 alone were expected with the addition of len to the treatment regimen. An immune response to the vaccine was seen in all patients treated with PVX-410 alone and is expected to be enhanced with PVX-410+len; these data will be presented. Based on the promising findings to date, an evaluation of PVX-410 in combination with an antibody to the programmed cell-death-1-ligand complex (PD1/PDL1) is planned to begin in 2015. Disclosures Nooka: Spectrum Pharmaceuticals: Consultancy; Onyx Pharmaceuticals: Consultancy. Off Label Use: Off label use of lenalidomide. Wang:Janssen: Honoraria; Pharmacyclics, Janssen, Celgene, Oncopep, Kite, Juno: Research Funding. Thomas:Novartis, Celgene, Acerta Pharmaceuticals, Idera Pharmaceuticals: Research Funding. O'Donnell:Millennium: Consultancy. Shah:Millenium: Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Array: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees. Kaufman:Milleniumm, Celgene, Novartis, Onyx, Spectrum: Consultancy. Lonial:Onyx: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Millennium: Consultancy, Research Funding. Richardson:Gentium S.p.A.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees. Raje:Takeda: Consultancy; BMS: Consultancy; Celgene Corporation: Consultancy; Amgen: Consultancy; Onyx: Consultancy; AstraZeneca: Research Funding; Millenium: Consultancy; Novartis: Consultancy; Acetylon: Research Funding; Eli Lilly: Research Funding.

scholarly journals International Survey for Strategies Used for Oral Anticoagulation Reversal in Children

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4976-4976
Author(s):  
Shveta Gupta ◽  
Ayesha Zia ◽  
Ravindra Sarode
Keyword(s):  
Board Of Directors ◽  
Vitamin K ◽  
Major Bleeding ◽  
Online Survey ◽  
Pediatric Population ◽  
Oral Anticoagulants ◽  
Off Label Use ◽  
Advisory Committees ◽  
Off Label ◽  
Label Use

Background: Vitamin K antagonists (VKA) have been the main stay of oral anticoagulation (OAC) in pediatrics. However, VKA have multiple challenges. The pharmacological properties of direct oral anticoagulants (DOACs) suggest that they may have advantages particularly for children. The off-label use of DOACs is however on the rise within the pediatric population. The increasingly broad and varied use of DOACs, lack of published clinical guidance, and limited data on reversal strategies have created the imperative to identify strategies for OAC reversal in pediatrics. We conducted an online survey for strategies used for oral anticoagulants reversal in pediatrics. Study Design: Institutional review board approval was obtained and an online survey was developed using the RedCap. The survey was electronically distributed by International Society of Hemostasis and Thrombosis (ISTH) to its Pediatric/Neonatal Thrombosis and Hemostasis Subcommittee group members. The survey questions asked approach to common hypothetical clinical scenarios for OAC reversal.The data were analysed descriptively. Results: There were 76 respondents, majority from academic free-standing Children'sHospitals. Seventy-two percent reported having a hemostasis-thrombosis/anticoagulation service but only 29 % have a dedicated anticoagulation pharmacist. Approximately 40% do not have a formal protocol in place for VKA reversal. For a supra-therapeutic INR (INR > 5) in a non-bleeding patient, 95% opted to manage by omitting the next dose of VKA while 18 % opted to give oral vitamin K alone or comitantly. For clinically relevant non-major bleeding, majority indicated using Vitamin K; oral (51%) or IV (37). For major bleeding on VKA, majority use either a combination of 4F-PCC and IV Vitamin K or plasma and IV Vitamin K (44/76 and 26/76 respectively). The presence of bleeding seemed to be the major driver for the choice of route (enteral versus parenteral) for Vitamin K for VKA reversal. Thirty-six of the 76 respondents indicated using DOACs; 94% used FXa inhibitors and 1/3 use dabigatran in their clinical practice. For non-urgent DOAC reversal, 97% indicated omitting the next dose. For non-major bleeding on DOAC, majority (29/36) indicated omitting the next dose/doses, some chose 4F-PCC (8/36) and only a few indicated use of specific reversal agents (3/36 and 1/36 for Dabigatran and Andexanet respectively). For major bleeding while on DOACs, the use of specific reversal agents (11/35, 6/35 for Andexanet and idarucizumab respectively) followed by 4F-PCC (9/35) was the major intervention indicated. Dilute thrombin time and partial thromboplastin time were the most commonly utilized tests to measure residual dabigatran activity. For Factor Xa inhibitors routine heparin assay rather than DOAC calibrated anti-Xa activity is utilized by most of the responders to assess presence of the plasma drug activity. Conclusion: Practices for oral anticoagulants reversal vary substantially in the pediatric population. Plasma is still used for urgent VKA reversal in many pediatric centers. The off-label use of DOACs in children is on the rise. Our results highlight the need for further studies to standardize OAC reversal in children. Disclosures Gupta: Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda-Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Research Funding; Novartis: Honoraria, Speakers Bureau; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees. Sarode:Portola: Honoraria; Octaphrarma: Consultancy; CSL Behring: Consultancy; Siemens: Research Funding. OffLabel Disclosure: The pharmacological properties of direct oral anticoagulants (DOACs) suggest that they may have advantages particularly for children. They are currently not approved in children. The off-label use of DOACs is however on the rise within the pediatric population.

Variation In Health-Related Quality of Life (HRQOL) by ISS Stage and ECOG Status Among Multiple Myeloma Patients.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3828-3828
Author(s):  
Chris L Pashos ◽  
Brian G. M. Durie ◽  
Robert M. Rifkin ◽  
Jatin J Shah ◽  
Thomas K. Street ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Self Care ◽  
Off Label Use ◽  
Advisory Committees ◽  
Off Label ◽  
Hrqol Data ◽  
Label Use

Abstract Abstract 3828 Introduction: Attention is being paid to HRQOL when monitoring hematologic disorders or the impact of treatments on those disorders. Minimal HRQOL data have been published on multiple myeloma (MM) patients (pts) in the United States (US). This analysis characterizes variation in the HRQOL of pts with active, symptomatic MM by International Staging System (ISS) stage and ECOG status. Methods: Data were collected as part of Connect MM®, a prospective observational registry initiated in September 2009 involving centers in the US. Data on pt demographics and clinical characteristics were provided by clinicians. HRQOL was reported by pts in the clinic at enrollment, within two months of diagnosis. Pts completed 3 psychometrically validated instruments: EQ-5D, Brief Pain Inventory (BPI), and Functional Assessment of Cancer Therapy-Multiple Myeloma (FACT-MM). Standard analyses were conducted of each instrument given clinical characteristics at that time. Reported mean BPI, EQ-5D and FACT-MM scores were analyzed by ISS and ECOG status. Statistical significance of score differences among sub-cohorts was ascertained by ANOVA using SAS 9.1. Results: HRQOL data were reported by 328 pts, enrolled from 135 centers. Pts were predominantly male (60%) and white (79%) with mean age at 67.3 (standard deviation [SD] 11.6) yrs. HRQOL scores by evaluable ISS stage (n=236) and ECOG status (n=258) are presented. BPI data (on a scale of 0 [no pain] to 10 [worst pain]) indicate that average reported pain worsens by ISS and ECOG severity. Mean EQ-5D scores (on a scale of 1 [no problem] to 2 [some problems] to 3 [incapacity]) indicate that pain/discomfort, and usual activities are most compromised, and with self care increase in severity as ISS and ECOG worsen. Anxiety/depression level is associated with ECOG, but not with ISS. FACT-MM results indicate that ISS and ECOG severity is associated with greater decrement in physical and functional domains. The associations of HRQOL with ECOG status were stronger than with ISS stage. Specifically, scores on the BPI, all EQ-5D domains, and all FACT-MM domains (except the social/family domain) were statistically significantly associated with more severe ECOG status. Conclusions: Initial results from the Connect MM® Registry indicate that HRQOL worsens with worsening ISS stage and ECOG status, especially in physical and functioning domains, pain/discomfort, and ability to conduct usual activities and to provide self care. These areas should receive attention at diagnosis. Future analyses should be conducted on: (1) more newly diagnosed patients; (2) how HRQOL may be affected over time with changes in disease; and, (3) how HRQOL may be influenced by alternative therapies. Results reported here should serve as useful baseline reference. Disclosures: Pashos: Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: CONNECT is a disease registry and includes data on off-label use of anti-myeloma agents. Durie:Celgene & Millennium: Consultancy. Rifkin:Millennium: Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau; Amgen: Speakers Bureau; Cephalon: Speakers Bureau; Dendreon: Speakers Bureau. Shah:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Research Funding. Street:Celgene: Employment. Sullivan:Celgene: Employment, Equity Ownership. Khan:Celgene Corporation: Employment.

scholarly journals Impact of Autologous Transplantation Vs. Chemotherapy Plus Lenalidomide in Newly Diagnosed Myeloma According to Patient Prognosis: Results of a Pooled Analysis of 2 Phase III Trials

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 198-198 ◽  
Author(s):  
Francesca Gay ◽  
Chiara Cerrato ◽  
Roman Hajek ◽  
Francesco Di Raimondo ◽  
Tommaso Caravita ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Stage I ◽  
Phase Iii ◽  
P Value ◽  
Off Label Use ◽  
Advisory Committees ◽  
Off Label ◽  
Cytogenetic Profile ◽  
Label Use

Abstract Background: Autologous stem cell transplantation (ASCT) improves outcome in comparison with chemotherapy (CC) innewly diagnosed multiple myeloma (NDMM) patients. The primary objective of our analysis was to compare progression-free survival (PFS) and overall survival (OS) of patients randomized to ASCT vs. chemotherapy (CC): we tested the hypothesis that benefit of ASCT could vary in different subsets of patients defined according to baseline prognostic features and response to induction. Methods: Data of 2 phase III multicenter randomized trials (RV-MM-PI-209 and RV-MM-EMN-441) enrolling patients younger than 65 years were pooled together. In both trials, patients received lenalidomide-dexamethasone induction and stem cell mobilization. Patients were randomized to either consolidation with 2 courses of Melphalan 200 mg/mq followed by ASCT (Mel200-ASCT) or 6 cycles of CC plus lenalidomide (CC+R) (RV-MM-PI-209: melphalan-prednisone-lenalidomide; RV-MM-EMN-441: cyclophosphamide-dexamethasone-lenalidomide). We evaluated PFS and OS of Mel200-ASCT vs. CC+R patients in the following subgroups, defined according to baseline features (Karnofsky performance status (PS) [60-70%, 80-100%], International Staging System (ISS) stage [I, II, III], cytogenetic profile [presence of del17 or t(4;14) or t(14;16); absence of del17, t(4;14) and t(14;16)]) and response to induction (≥very good partial response [VGPR], <VGPR). Data cut-off was June, 2014. Results: 791 patients were enrolled in the two trials; 529 were eligible for consolidation: 268 patients received Mel200-ASCT and 261 patients received CC+R. Median follow-up for survivors was 4 years. Mel200-ASCT significantly prolonged PFS (median: 42 vs. 24 months, HR 0.52, 95%CI 0.41-0.65, P<0.001) and OS (4-year: 83% vs. 68%, HR 0.59, 95%CI 0.40-0.90 P=0.012) in comparison with CC+R. Mel200-ASCT significantly improved PFS in all the subgroups of patients analyzed. (Table). The most significant OS benefit was noticed in patients with a Karnofsky PS 80-100% (4-year: 85% vs. 73%, HR 0.55, 95% CI 0.35-0.88, P=0.013), with ISS Stage I disease (4-year: OS 89% vs. 77%, HR 0.43, 95% CI 0.20-0.91, P=0.027), with absence of del17, t(4;14) and t(14;16) (4-year: 87% vs. 78%, HR 0.57, 0.33-0.98, P=0.040), and in patients achieving ≥VGPR after lenalidomide-dexamethasone induction (4-year: 84% vs. 65%, HR 0.46, 95% CI 0.22-0.96, P=0.039). Conclusions: In NDMM patients, Mel200-ASCT significantly improved PFS and OS in comparison with CC+R. The most significant OS advantage was observed in patients with baseline Karnofsky PS 80-100%, ISS Stage I, with absence of del17, t(4;14) or t(14;16) and in patients achieving ≥VGPR after induction. These data suggest intensifying treatment in good-prognosis patients and in patients with a chemo-sensitive disease. More effective novel agents are needed for patients with a more aggressive disease. Table Subgroup analysis of PFS and OS in Mel200-ASCT vs CC+R patients PFS OS HR 95% CI P-value HR 95% CI P-value ISS Stage I Stage II Stage III 0.430.610.60 0.30-0.630.42-0.900.36-0.98 <0.0010.0120.042 0.430.690.75 0.20-0.910.33-1.420.38-1.47 0.0270.3150.397 Cytogenetic profile No del17, t(4;14), t(14;16) Del17 or t(4;14) or t(14;16) 0.610.44 0.44-0.860.27-0.70 0.004<0.001 0.570.60 0.33-0.980.31-1.15 0.0400.120 Karnofsky PS 60-70% 80-100% 0.460.52 0.26-0.810.40-0.68 0.008<0.001 0.720.55 0.29-1.730.35-0.88 0.4500.013 Response to induction ≥VGPR<VGPR 0.480.53 0.30-0.800.40-0.70 <0.001<0.001 0.460.71 0.22-0.960.43-1.18 0.0390.193 Disclosures Gay: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Sanofi: Membership on an entity's Board of Directors or advisory committees. Off Label Use: Off-label use of Lenalidomide.. Hajek:Janssen: Honoraria; Celgene: Consultancy, Honoraria; Merck: Consultancy, Honoraria. Di Raimondo:Janssen-Cilag: Honoraria; Celgene: Honoraria. Caravita:Celgene: Honoraria. Patriarca:Merck Sharp & Dohme: Honoraria; Janssen and Cilag: Honoraria; Celgene: Honoraria. Offidani:Janssen-Cilag: Honoraria; Mundipharma: Honoraria; Amgen: Honoraria; Sanofi: Honoraria; Novartis: Honoraria; Celgene: Honoraria. Ria:Janssen-Cilag: Consultancy; Novartis: Consultancy; Italfarmaco: Consultancy; Celgene: Consultancy. Cavallo:Onyx: Honoraria; Janssen-Cilag: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Petrucci:Bristol-Myers Squibb: Honoraria; Sanofi: Honoraria; Celgene: Honoraria; Janssen-Cilag: Honoraria. Boccadoro:Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: 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. Spencer:Celgene: Honoraria. Palumbo:Sanofi Aventis: Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Array BioPharma: Honoraria; Genmab A/S: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria; Onyx Pharmaceuticals: Consultancy, Honoraria; Amgen: Consultancy, Honoraria.

scholarly journals Increasing off-label use of antipsychotic medications in the United States, 1995-2008

2011 ◽  
Vol 20 (2) ◽  
pp. 177-184 ◽  
Author(s):  
G. C. Alexander ◽  
S. A. Gallagher ◽  
A. Mascola ◽  
R. M. Moloney ◽  
R. S. Stafford
Keyword(s):  
United States ◽  
The United States ◽  
Off Label Use ◽  
Antipsychotic Medications ◽  
Off Label ◽  
Label Use

scholarly journals Off-label use of cancer therapies in women diagnosed with breast cancer in the United States

SpringerPlus ◽  
2015 ◽  
Vol 4 (1) ◽  
Author(s):  
Sophie Hamel ◽  
Douglas S McNair ◽  
Nicholas J Birkett ◽  
Donald R Mattison ◽  
Anthony Krantis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
United States ◽  
The United States ◽  
Cancer Therapies ◽  
Off Label Use ◽  
Off Label ◽  
Label Use

scholarly journals Facts about Magnesium Sulfate: Time to Revise the Safety Concern in Obstetric Use

2014 ◽  
Vol 4 (3) ◽  
pp. 177-183
Author(s):  
Zaida Rahman ◽  
Asadul Mazid Helali
Keyword(s):  
Pregnant Women ◽  
Magnesium Sulfate ◽  
Preterm Labor ◽  
Safety Concern ◽  
Safety Information ◽  
Harmful Effect ◽  
The United States ◽  
Off Label Use ◽  
Off Label ◽  
Label Use

Magnesium sulfate (MgSO4) is the agent most commonly used for treatment of eclampsia and prevention of eclampsia in patients with severe pre-eclampsia. Another commonly practiced offlabel use of this drug is in preventing preterm labor in pregnant women where the duration of the treatment might be more than one week. It is usually given either by intramuscular or intravenous route. After administration, about 40% of plasma magnesium is bound with protein. The unbound magnesium ion diffuses into the extravascular extracellular space and then diffuses into bone. It also crosses the placenta and fetal membranes and then diffuses into the fetus and amniotic fluid. Magnesium is almost exclusively excreted in the urine; 90% of the dose is excreted during the first 24 hours after an intravenous infusion of MgSO4. The clinical effect and toxicity of MgSO4 can be linked to its concentration in plasma. A concentration of 1.8–3.0 mmol/L has been suggested for treatment of eclampsia. The actual magnesium dose and concentration needed for prophylaxis have never been estimated. Maternal toxicity is rare when MgSO4 is carefully administered and monitored. Deep tendon reflexes, respiratory rate, urine output and serum concentrations are the most common variables for monitoring the toxic effect. Currently the United States (US) Food and Drug Administration (FDA) is advising health care professionals against using MgSO4 injection for more than 5–7 days to stop preterm labor in pregnant women (off-label use). Administration of MgSO4 injection to pregnant women for more than 5–7 days may lead to low calcium levels and bone problems in the fetus, including osteopenia and fractures. The harmful effect in the fetus with the shortest duration is not established. In light of this new safety information, the drug label for MgSO4 injection, USP 50% has also been changed, including changing the pregnancy category to D from A and denoting the effect as “New teratogenic effects”. Similarly, the manufacturers of other MgSO4 injection products have made similar changes to their drug labels. In this review, the currently available knowledge of the pharmacokinetics of MgSO4 and its clinical usage for women with pre-eclampsia and eclampsia, its off-label use and safety concern regarding the warning announced by the FDA will be outlined. DOI: http://dx.doi.org/10.3329/jemc.v4i3.20957 J Enam Med Col 2014; 4(3): 177-183

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