Abstract WMP83: Rivaroxaban Therapy Is Not Associated with Hemorrhagic Transformation After Acute Cardioembolic Stroke: A Prospective MRI Study

Introduction: Early anticoagulation after cardioembolic stroke remains controversial, due to the potential for symptomatic hemorrhagic transformation (HT). The safety profile of rivaroxaban within 14 days of cardioembolic stroke onset has not been assessed prospectively. Methods: We conducted a prospective, open label study of patients with atrial fibrillation treated with rivaroxaban ≤14 days of mild/moderate ischemic stroke/TIA (NIHSS score≤8) onset. Informed consent was obtained after the decision to treat with rivaroxaban was made by the treating physician. All patients underwent MRI, including susceptibility-weighted sequences, within 24 hours of rivaroxaban initiation and at day 7, with clinical assessment at 90 days. HT was classified using ECASS criteria (hemorrhagic infarct (HI) 1/2, or parenchymal hemorrhage (PH) 1/2). The primary endpoint was symptomatic HT (defined as PH2 associated with an NIHSS increase ≥4 within the study period). Secondary outcomes included any PH at day 7 and recurrent stroke within 90 days of enrolment. Results: Sixty patients were enrolled (mean±SD age 71±19 years, 82% stroke/18% TIA). Median (IQR) time from onset to first rivaroxaban dose was 3(5) days. At treatment initiation, median NIHSS was 2(4) and median DWI volume was 7.9(13.7) ml (range 0-175 ml). Baseline DWI volume was correlated with time to first dose (r=0.58, p<0.001). On baseline MRI, HT was present in 25 patients (42%) (HI1=19, HI2=6). Fifty patients had follow-up MRI at a median 7(4) days after rivaroxaban initiation (4 patients withdrew consent and 6 were lost to follow-up). No patients developed symptomatic HT or PH at any point. New asymptomatic HI1 developed in 3 patients. There was asymptomatic progression from HI1 to HI2 in 5 patients. In the remaining 18 patients with baseline HI and follow-up MRI, there was no change at day 7. Two recurrent ischemic strokes occurred (day 5 and day 28). Two additional patients had new asymptomatic DWI lesions at day 7. Two patients died within 90 days (one recurrent stroke and one pneumonia). Conclusion: These data support the safety of rivaroxaban initiation within 14 days of mild/moderate cardioembolic stroke/TIA. MRI evidence of petechial HT, which is common, does not appear to increase the risk of symptomatic HT.

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Phase 2 dose multi-center, open-label study of ARQ 501, a checkpoint activator, in adult patients with persistent, recurrent or metastatic leiomyosarcoma (LMS)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.20521 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 20521-20521 ◽

Cited By ~ 15

Author(s):

L. P. Hartner ◽

L. Rosen ◽

M. Hensley ◽

D. Mendelson ◽

A. P. Staddon ◽

...

Keyword(s):

Clinical Investigation ◽

Phase 1 ◽

Phase 2 ◽

Open Label ◽

Open Label Study ◽

Apoptotic Protein ◽

Three Phase ◽

Phase 2 Study ◽

Lost To Follow Up

20521 Background: ARQ 501 selectively induces apoptosis in cancer cells by inducing a rapid and sustained increase of the pro- apoptotic protein E2F-1. ARQ 501 has been studied in three phase 1 studies, demonstrating acceptable toxicity and encouraging signs of efficacy. A 54 y/o female with metastatic LMS who failed 7 previous therapies achieved a prolonged PR on ARQ 501 monotherapy. This was consistent with preclinical data, where induction of E2F-1 and corresponding efficacy in human leiomyosarcoma xenografts was observed. Methods: A phase 2 study in adult LMS patients (>3 prior systemic therapies) was initiated to assess ORR, TTP and further characterize the safety of ARQ 501. ORR included CR, PR and SD=4 mo. Four week cycles (ARQ 501 450mg/m2) were repeated until progression, unacceptable toxicity, or another discontinuation criterion. Results: 49 patients were enrolled and 45 received ARQ 501. Data is available for 43 patients (4M/39F, median age, 54). Of the 43, 10 did not reach a protocol defined tumor assessment (4 deaths, 5 PD and 1 lost to follow-up prior to week 8), 19 have been assessed for response per RECIST at eight weeks (7 SD of 8–28+ weeks, 1 PR, 11 PD) and 14 active patients yet to reach first tumor assessment. The most common AEs were: anemia (68%, 21%=G3), hyperbilirubinemia (35%, 6%=G3), fatigue (35%, 0%=G3), nausea (30%, 0%=G3), constipation (24%), hemolysis (21%, 6%=G3), dyspnea (21%), and vomiting (21%). One treatment related death was reported in a 47 y/o Asian male with severe hemolysis following a single infusion of ARQ 501 at 450 mg/m2. The pt was hospitalized, but severe hemolysis led to acute renal failure and the patient expired after 4 days. Conclusions: ARQ 501 was administered to 45 patients with advanced, recurrent or persistent leiomyosarcoma. Several patients have achieved some clinical benefit (1 PR, 3 prolonged SD), further analysis of efficacy data is warranted prior to additional clinical investigation. No significant financial relationships to disclose.

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Intralesional Triamcinolone for Fistulous Tracts in Hidradenitis Suppurativa: An Uncontrolled Prospective Trial with Clinical and Ultrasonographic Follow-Up

Dermatology ◽

10.1159/000499934 ◽

2019 ◽

Vol 236 (1) ◽

pp. 46-51 ◽

Cited By ~ 2

Author(s):

Pedro Álvarez ◽

F. Javier García-Martínez ◽

Ines Poveda ◽

José Carlos Pascual

Keyword(s):

Hidradenitis Suppurativa ◽

Single Injection ◽

Small Sample Size ◽

Prospective Trial ◽

Small Sample ◽

Control Group ◽

Open Label ◽

Open Label Study ◽

Lost To Follow Up

Background: There is little evidence on the use of intralesional triamcinolone (ILT) for managing fistulous tracts in hidradenitis suppurativa (HS). Objective: To assess the clinical and ultrasound response to ILT for single fistulous lesions in HS patients. Methods: A prospective open-label study was conducted to assess response to ILT (40 mg/mL) for fistulous tracts in HS. Consecutive patients (Hurley II stage exclusively) presenting to our department were recruited from August 2016 to August 2018. They received a single injection of ILT as the sole treatment. Lesions were assessed clinically and by ultrasound at baseline and 90 days. Results: Of the 53 included HS patients with fistulous tracts, 36 (67.9%) were women, 30 (56.6%) were smokers, and 36 (67.9%) were obese or overweight (body mass index ≥25). Median Sartorius score was 9.0 (IQR 9.0–36.0), and median duration of the lesion treated was 6 months (IQR 3.0–12.0). Fistulous tracts were injected with 0.5 mL triamcinolone 40 mg/mL. Seven patients were lost to follow-up. At 90 days, 20 (43.5%) lesions showed clinical and ultrasound resolution, 13 (28.3%) showed only clinical resolution while persisting on ultrasound, and 13 (28.3%) persisted both clinically and on ultrasound. Mean clinical size decreased from 17.0 to 5.1 mm (p < 0.0001), while mean length on ultrasound decreased from 16.0 to 8.6 mm (p < 0.0001). Limitations: Small sample size and no control group. Conclusions: Our study suggests that ILT is beneficial for small fistulous tracts in HS.

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Successful long-term remission through tapering tocilizumab infusions: a single center prospective study

10.21203/rs.2.12756/v1 ◽

2019 ◽

Author(s):

Chayma Ladhari ◽

Pierre Le Blay ◽

Thierry Vincent ◽

Ahmed Larbi ◽

Emma Rubenstein ◽

...

Keyword(s):

Therapeutic Option ◽

Sustained Remission ◽

Single Center ◽

Open Label ◽

Open Label Study ◽

Treatment Interval ◽

Secondary Failure ◽

Term Maintenance

Abstract Background Strategic drug therapy for rheumatoid arthritis (RA) patients with prolonged remission is not well defined. According to recent guidelines, tapering biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs) may be considered. We aimed to evaluate the long-term maintenance of tocilizumab (TCZ) treatment after the progressive tapering of infusions. Methods We conducted an exploratory, prospective, single-center, open label study, on RA patients with sustained remission for at least 3 months and treated with TCZ infusions every 4 weeks. The initial re-treatment interval was 6 weeks for the first 3 months. Thereafter, the spacing between infusions was determined by the clinician. Successful long-term maintenance following the tapering of TCZ infusions was defined by patients still treated after two years by TCZ with a minimum dosing interval of 5 weeks. Results Thirteen patients were enrolled in the study. Eight out of thirteen were still treated by TCZ after two years. Successful long-term maintenance was possible in six patients, with four patients maintaining a re-treatment interval of 8-weeks or more. We observed 5 patients with TCZ withdrawal: one for adverse drug reaction (neutropenia) and four with secondary failure. Patients achieving successful long-term maintenance with TCZ were significantly younger than those with secondary failure (p<0.05). In addition, RA patients with positive rheumatoid factor and anti-citrullinated peptide antibodies, experienced a significantly greater number of flares during our 2-year follow-up (p<0.01). Conclusions A progressive tapering of TCZ infusions seems possible in most of the patients. However, larger studies, including more patients, are needed to confirm this therapeutic option.

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ATIM-37. PHASE II, OPEN-LABEL, SINGLE ARM, MULTICENTER STUDY OF AVELUMAB WITH HYPOFRACTIONATED RADIATION (HFRT) FOR ADULT PATIENTS WITH SECONDARILY TRANSFORMED IDH-MUTANT GLIOBLASTOMA (GBM)

Neuro-Oncology ◽

10.1093/neuonc/noz175.036 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi9-vi10

Author(s):

Sylvia Kurz ◽

Joshua S Silverman ◽

Tsivia Hochman ◽

Lakshmi Nayak ◽

Isabel Arrillaga-Romany ◽

...

Keyword(s):

Phase Ii ◽

Multicenter Study ◽

Somatic Mutations ◽

Treatment Initiation ◽

Adult Patients ◽

Open Label ◽

Grade 3 ◽

Hypofractionated Radiation ◽

Dose Limiting Toxicity

Abstract BACKGROUND There is no effective therapy for patients (pts) with IDH-mutant gliomas that progress after RT and chemotherapy. At time of progression, these tumors have often transformed to glioblastoma (GBM) and have increased numbers of somatic mutations, i.e. have a “hypermutator phenotype”. We hypothesized that there is synergistic efficacy of Avelumab (anti-PD-L1) combined with HFRT in pts with secondarily transformed IDH-mutant GBMs. Safety-lead-in results will be presented. METHODS This is a phase II, open-label, single-arm, multicenter study of Avelumab with HFRT in adults with transformed IDH-mutant GBM who previously received RT and TMZ and/or PCV. All pts received Avelumab 10 mg/kg IV followed at Day 8 by HFRT (25 Gy in 5 daily 5-Gy fractions) and then Avelumab 10 mg/kg IV every 2 weeks. A 3 + 3 design was used for a 6-patient safety-lead-in cohort. Adverse events were recorded according to CTCAE. RESULTS Six pts (F=4, M=2) with a median age= 45.5 yrs (range 31.5–54.4 yrs) were enrolled in the safety-lead-in cohort. No DLT was observed. Grade ≥ 3 AEs included increased cerebral edema (3 pts), hyponatremia (1 pt) and worsening hemiparesis (3 pts). Grade ≤ 2 AEs included nausea, hypothyroidism, lymphopenia, thrombocytopenia, transaminase elevation, and fever/chills. Median follow-up time was 8.9 mo. Best treatment response was SD in 1 patient. At time of last follow-up all pts have discontinued treatment for PD. Median PFS was 4.2 mo (range 1.4–5.7). Median OS was 10.1 (range 6.8–21+) mo. 4 pts (67%) died, 2 pts remain alive in follow-up at 6.9 and 21.6 months after treatment initiation. The study was closed after the safety lead-in completed enrollment due to slow accrual. CONCLUSIONS Avelumab combined with HFRT was tolerable without dose-limiting toxicity in this safety-lead-in cohort of adult patients with transformed IDH-mutant GBM. Further studies are necessary to determine efficacy of this treatment regimen.

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Bortezomib, thalidomide, and dexamethasone followed by double autologous haematopoietic stem-cell transplantation for newly diagnosed multiple myeloma (GIMEMA-MMY-3006): long-term follow-up analysis of a randomised phase 3, open-label study

The Lancet Haematology ◽

10.1016/s2352-3026(20)30323-9 ◽

2020 ◽

Vol 7 (12) ◽

pp. e861-e873 ◽

Cited By ~ 1

Author(s):

Paola Tacchetti ◽

Lucia Pantani ◽

Francesca Patriarca ◽

Maria Teresa Petrucci ◽

Elena Zamagni ◽

...

Keyword(s):

Haematopoietic Stem Cell Transplantation ◽

Haematopoietic Stem Cell ◽

Newly Diagnosed ◽

Open Label ◽

Phase 3 ◽

Open Label Study ◽

Label Study ◽

Long Term Follow Up

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Follow-up results of myositis patients treated with H. P. Acthar gel

Rheumatology ◽

10.1093/rheumatology/keaa076 ◽

2020 ◽

Vol 59 (10) ◽

pp. 2976-2981 ◽

Cited By ~ 1

Author(s):

Didem Saygin ◽

Chester V Oddis ◽

Galina Marder ◽

Siamak Moghadam-Kia ◽

Preeya Nandkumar ◽

...

Keyword(s):

Standard Dose ◽

Manual Muscle Testing ◽

Open Label ◽

Muscle Testing ◽

Core Set ◽

Minimal Improvement ◽

Definition Of ◽

Post Trial ◽

Lost To Follow Up

Abstract Objectives Idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases characterized by proximal muscle weakness. H. P. Acthar gel [repository corticotropin injection (RCI)] is a formulation of adrenocorticotropic hormone and has been approved by Food and Drug Administration for use in IIM; however, literature is limited. In this study, we report longitudinal follow-up of myositis patients treated with RCI. Methods Patients with refractory IIM who were enrolled in the prospective, open-label RCI trial were included in this study. The post-trial follow-up period was 6 months with assessments every 2 months, which included myositis core set measures including extra-muscular global, muscle and patient global disease activities, HAQ, and manual muscle testing. Results Two patients were lost to follow-up after finalization of the trial, and the remaining eight patients were enrolled in the follow-up study. One patient remained on RCI after the trial. In the follow-up period, four of eight patients had flare at on average 4.1 months after the RCI trial. Among the patients who flared, three required an increase in prednisone. One patient was restarted on RCI at 5.5 months, but had minimal improvement after 3 months. Four patients who remained stable continued to satisfy criteria for the definition of improvement through the 6-month follow-up. However, none showed any further improvement in the primary or secondary efficacy outcomes after the initial RCI trial. Conclusion To our knowledge, this is the first study reporting the follow-up results of patients treated with standard dose and duration of Acthar. We believe that our study will provide the basis for the development of future randomized RCI trials in IIM.

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Once-daily etravirine/raltegravir (400/800 mg q24h) dual therapy maintains viral suppression over 48 weeks in HIV-infected patients switching from a twice-daily etravirine/raltegravir (200/400 mg q12h) regimen

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa423 ◽

2020 ◽

Author(s):

Romain Palich ◽

Clotilde Allavena ◽

Gilles Peytavin ◽

Cathia Soulie ◽

Roland Tubiana ◽

...

Keyword(s):

Success Rate ◽

Primary Outcome ◽

Viral Suppression ◽

Dual Therapy ◽

Open Label ◽

Once Daily ◽

Drug Concentrations ◽

Highly Effective ◽

Lost To Follow Up

Abstract Background Etravirine/raltegravir dual therapy has been shown to be highly effective as a twice-daily (q12h) regimen in suppressed HIV-infected patients enrolled in the ANRS-163 study. Objectives As a once-daily (q24h) regimen is easier for daily life, we aimed to evaluate the capacity of etravirine/raltegravir (400/800 mg) q24h to maintain viral suppression in patients on etravirine/raltegravir q12h. Methods Patients on a suppressive etravirine/raltegravir q12h regimen for at least 96 weeks were switched to etravirine/raltegravir q24h in this prospective, multicentre, open-label, single-arm study. Primary outcome was the rate of virological failure (VF: confirmed pVL >50 copies/mL, single pVL >400 copies/mL or single pVL >50 copies/mL with ART change) at Week 48 (W48). Secondary outcomes included treatment strategy success rate (no VF and no treatment discontinuation), regimen tolerability, plasma drug concentrations and resistance profile in the case of VF. Results A total of 111 patients were enrolled, with a median (IQR) age of 57 years (52–62), CD4 count of 710 cells/mm3 (501–919) and viral suppression for 7.9 years (5.9–10.7). Two patients experienced viral rebound at W24 and W48, leading to a VF rate of 2.0% (95% CI 0.5–7.8) at W48, associated with INSTI resistance in one case. Both had past NNRTI mutations. Ten patients discontinued treatment for adverse events (n = 2), investigator or patient decisions (n = 3), lost to follow-up (n = 3), death (n = 1) or pregnancy (n = 1). Overall, the strategy success rate was 89% (95% CI 81.5–93.6) at W48. In a subgroup of 64 patients, median (IQR) plasma C24h concentrations were 401 ng/mL (280–603) for etravirine and 62 ng/mL (31–140) for raltegravir. Conclusions Switching patients virally suppressed on etravirine/raltegravir q12h to the same regimen but given q24h was highly effective in maintaining virological suppression in HIV-infected patients.

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Tuberculosis Case Finding Cascade and Treatment Outcomes among Male Inmates in Two Prisons in Zimbabwe

Tuberculosis Research and Treatment ◽

10.1155/2020/5829471 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Alois Mandizvidza ◽

Riitta A. Dlodlo ◽

Palanivel Chinnakali ◽

Hamufare Dumisani Mugauri ◽

Freeman Dube ◽

...

Keyword(s):

Treatment Outcomes ◽

Treatment Initiation ◽

Treatment Success ◽

Molecular Testing ◽

Tuberculosis Case ◽

Missed Opportunities ◽

Male Inmates ◽

Almost All ◽

Lost To Follow Up

Setting. Zimbabwe is a high tuberculosis (TB) burden country, with an estimated prevalence of 344/100,000 population. Though prisons are known high-prevalence sites for TB, the paucity of data affects the quantification of the disease and treatment outcomes in these settings. We measured the prevalence of TB disease and treatment outcomes among inmates at two major prisons in Harare, Zimbabwe. Design. A cohort study using programmatic data was undertaken to assess TB diagnostic cascade in one of the study prisons for 2018. Treatment outcomes among male inmates with TB were assessed over a period of four years, in two study prisons. Results. A total of 405 (11%) inmates with presumptive TB were identified, and 370 (91%) of these were evaluated for TB, mostly using rapid molecular testing of sputum specimens. Twenty-five inmates were diagnosed with TB resulting in a prevalence of 649/100,000 population. Of these, 16 (64%) were started on treatment. Nine (36%) were lost to follow-up before treatment initiation. From 2015 to 2018, 280 adult male inmates with TB were started on treatment. Of these, 212 (76%) had pulmonary disease that was bacteriologically confirmed. Almost all (276/280, 99%) had known HIV status, 65% were HIV-infected, and 80% of these were on antiretroviral treatment. The TB treatment success rate (cured or treatment completed) was recorded for 209 (75%) inmates, whilst 14 (5%) died and 11 (4%) were lost to follow-up. The frequency of unfavourable treatment outcomes (death, lost to follow-up, and not evaluated) was higher (54%) among inmates≥60 years than those in the age group of 45-59 years (17%). Conclusion. The findings revealed a threefold burden of TB in prisons, compared with what is reported by national survey. To decrease transmission of TB bacilli, it is essential to promote efforts that address missed opportunities in the TB diagnostic cascade, prompt treatment initiation, and ensure that tracking and documentation of treatment outcomes for all inmates are intensified.

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