bluuebunny/crossref_metadata_2025_split huggingface dataset:
PF604 THE AUSTRALASIAN LEUKAEMIA AND LYMPHOMA (ALLG) GROUP MM17 TRIAL: RESPONSE ADAPTIVE SALVAGE WITH CARFILZOMIB‐THALIDOMIDE‐DEXAMETHASONE FOR MULTIPLE MYELOMA PATIENTS FAILING FRONT‐LINE BORTEZOMIB
Authors: Spencer A. , Quach H. , Horvath N. , Kerridge I. , Yuen F. , Lee E. , Morris E. , Kalff A. , Bergin K. , Sirdesai S. , Gorniak M. , Mithraprabhu S. , Khong T. , Reynolds J. 
Published: June 2019

Background:Over 90% of transplant eligible newly diagnosed multiple myeloma (TE‐NDMM) patients (pts) in Australia are induced with bortezomib (V)‐ cyclophosphamide‐dexamethasone. Of these, 15% demonstrate either a sub‐optimal response (<partial response [PR]) (SOR) or primary refractoriness (1REF). These pts experience short progression free (PFS) and overall survival (OS), thus representing an area of ongoing unmet medical need.Aims:The ALLG MM17 trial was designed to evaluate an early response adaptive switch to carfilzomib‐thalidomide‐dexamethasone (KTd) and to define the mutational spectrum of disease in TE‐ NDMM patients failing V‐induction.Methods:Pts were either SOR (defined as 2on D1, 2, 8, 9, 15 and 16 of each 28‐day cycle (27 mg/m2D1 and 2 of cycle 1); T 100 mg D1–28; and, d 40 mg on D1, 8, 15, and 22 of each cycle. Pts were planned to receive KTd x 4 cycles then undergo re‐staging. Those achieving a stringent complete response (sCR) (morphologically normal bone marrow [BM], IF negativity, normalisation of the involved light chain isotype) proceeded to a MEL200 ASCT. Those withResults:Fifty pts were recruited between 9/2016 and 4/2018. Data cut‐off date was November 7, 2018 with the reverse‐Kaplan‐Meier estimate of the median potential follow‐up for survival being 14.8 months (95% CI: 9.7 – 17.8 months). Median age was 50 years (36–71) with 72% males. Median time from initial therapy to study entry was 4 months with disease status at entry of SOR in 26 (66%) (<MR n = 13, <PR n = 13) and 1REF in 13 (33%). EMC92 stratification demonstrated high‐risk disease in 48%. The tumour suppressor CDC27 (Anaphase‐promoting complex E3 ubiquitin ligase) was the most commonly mutated gene at study entry with a high proportion of patients also manifesting potentially targetable lesions – ATR, ATM, PIK3CA, FGFR3 and KRAS. The median number of pre‐ASCT KTd cycles was 6 (range 1 to 6). ORR was 78% (95% CI: 64–87%)∗‐ sCR 12%, CR 6%, VGPR 38% and PR 22%. On an intention‐to‐treat basis 32% of pts were MRD neg pre‐ASCT, 40% at day 100 post‐ASCT and 51% post KTd consolidation. Ten pts have progressed, 7 with highly aggressive extra‐medullary disease. No patient that achieved MRD negativity has progressed. Neither median PFS nor OS have been reached.Summary/Conclusion:KTd produces high response rates and MRD negativity in TE‐NDMM patients failing V‐based induction. TAS revealed a novel mutational spectrum consistent with treatment selection of V‐resistant sub‐clones likely present at diagnosis.
PF612 ONCE‐WEEKLY (70 MG/M2) VERSUS TWICE‐WEEKLY (56 MG/M2) DOSING OF CARFILZOMIB FOR PATIENTS WITH RELAPSED AND/OR REFRACTORY MULTIPLE MYELOMA
Authors: Moreau P. , Stewart A.K. , Dimopoulos M.‐A. , Siegel D. , Facon T. , Berenson J. , Raje N. , Berdeja J.G. , Orlowski R.Z. , Yang H. , Ma H. , Klippel Z. , Zahlten‐Kumeli A. , Mezzi K. , Iskander K. , Mateos M.‐V. 
Published: June 2019

Background:Carfilzomib (CFZ) combined with dexamethasone is approved to treat patients (pts) with relapsed and/or refractory multiple myeloma (RRMM), with CFZ given once‐weekly at 70 mg/m2 (Kd70 QW) or twice‐weekly at 56 mg/m2 (Kd56 BIW). No randomized trials have directly compared Kd70 QW with Kd56 BIW.Aims:We performed a post hoc comparison between pts who received Kd56 BIW in the ENDEAVOR trial and pts who received Kd70 QW in the A.R.R.O.W. or CHAMPION‐1 trials.Methods:Data were analyzed from 3 trials of CFZ in RRMM: A.R.R.O.W. (240 pts in Kd70 QW arm; 2–3 prior therapies and refractory to most recent therapy), CHAMPION‐1 (104 pts received Kd70 QW; 1–3 prior therapies), and ENDEAVOR (464 pts in Kd56 BIW arm; 1–3 prior therapies). Pts who received Kd70 QW in A.R.R.O.W. and CHAMPION‐1 were pooled and compared with pts who received Kd56 BIW in ENDEAVOR. As study populations slightly varied among the 3 trials, an analysis of safety and efficacy was performed in a subgroup of pts who received 2–3 prior therapy lines and were not refractory to bortezomib (BTZ). Also, we performed regression analyses (controlling for age, ISS stage, BTZ and lenalidomide refractory status, and number of prior regimens) among all pts in the trials who received Kd70 QW or Kd56 BIW.Results:Among BTZ non‐refractory pts with 2–3 lines of prior therapy, median progression‐free survival (PFS) was 12.1 months (95% CI 8.4–14.3) for Kd70 QW (n = 146) and 14.5 months (95% CI 10.2–NE) for Kd56 BIW (n = 217), and the overall response rate (ORR) was 69.9% (95% CI 61.7–77.2) for Kd70 QW and 72.4% (95% CI 65.9–78.2) for Kd56 BIW. The rate of grade ≥3 adverse events (Kd70 QW vs Kd56 BIW) was 67.6% and 85.3%; among adverse events of interest, the grade ≥3 rate was 1.4% and 5.1% for cardiac failure, 3.4% and 6.0% for renal failure, and 5.5% and 15.7% for hypertension. Kd70 QW represents a convenient and well‐tolerated treatment modality for pts with RRMM. In a Cox proportional hazards model, the hazard ratio for PFS (Kd70 QW vs Kd56 BIW) was 0.91 (95% CI 0.69–1.19), and in a logistic regression model the odds ratio for ORR (Kd70 QW vs Kd56 BIW) was 1.12 (95% CI 0.74–1.69).Summary/Conclusion:This post hoc analysis suggests that once‐weekly Kd70 has a comparable benefit‐risk profile to twice‐weekly Kd56.© 2019 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2019 ASCO Annual Meeting. All rights reserved.
PF613 CLINICAL UTILITY OF [18F]FLORBETABEN PET/CT SCAN FOR IMAGING AMYLOIDOSIS IN MULTIPLE MYELOMA PATIENTS
Authors: Jo J.‐C. , Seo M. , Choi Y.S. , Lee Y.J. , Park S.H. , Cha H.J. , Park S.H. 
Published: June 2019

Background:[18F]Florbetaben is a positron emission tomography (PET) tracer that specifically binds to amyloid beta‐pleated structure. Diagnosis of immunoglobulin light‐chain amyloidosis in patients with multiple myeloma (MM) is clinically important to manage symptoms and signs associated with amlyoidosis.Aims:We aimed to evaluate the feasibility of [18F]Florbetaben PET for detecting amyloid deposits in MM patients and to explore the most optimal method for PET analysis.Methods:Fourteen patients with multiple myeloma were prospectively enrolled (6 patients with amyloidosis and 8 controls) between Aug 2018 and Nov 2018. After injection of 300 MBq of [18F]Florbetaben, dynamic imaging of the kidneys was acquired for 20 minutes. Time‐activity curve was generated by using a region of interest placed over the kidney and retention index (RI) was obtained. At 90 minutes post‐injection, PET image was acquired, with a scan field from the vertex to mid‐thigh. All images were assessed both qualitatively and quantitatively. Comparison between amyloidosis and non‐amyloidosis groups was performed, regarding SUVmax, SUVmean, and SUV ratio (SUVR = tissue of interest/reference region), which were obtained from both sphere and manually drawn volumes of interest (VOI). Amyloid deposition was confirmed according to international consensus guidelines.Results:All patients in the control group did not show any abnormal amyloid uptake on 18F‐Florbetaben PET/CT (0/8), while those in the amyloid group had amyloid positive findings in more than one organ (6/6, 100%). Among 15 organs confirmed to have amyloidosis involvement prior to PET/CT, 9 were positive on 18F‐Florbetaben PET/CT. The detection rates of amyloidosis involvement in the heart, stomach, and tongue were excellent (100%), whereas those of the liver, esophagus, and colon were poor. 18F‐Florbetaben PET/CT found 12 unexpected abnormal amyloid uptakes in the tongue, thyroid, heart, lung, stomach, and spleen. Three of these 12 unexpected uptakes were later clinically determined to be amyloidosis (1 tongue, 1 heart, and 1 lung).Summary/Conclusion:[18F]Florbetaben PET can be one of the tool to detect systemic amyloid deposits in MM patients, especially in the heart, stomach, and tongue.
PF618 PROGNOSTIC IMPACT OF 18F‐FDG PET/CT IN PATIENTS WITH MULTIPLE MYELOMA PRESENTING WITH RENAL IMPAIRMENT
Authors: Jung S.‐H. , Ahn S.‐Y. , Song G.‐Y. , Heo M.H. , Yang D.‐H. , Ahn J.‐S. , Kim H.‐J. , Lee J.‐J. 
Published: June 2019

Background:18F‐fluorodeoxyglucose (18F‐FDG) positron emission tomography/computed tomography (PET/CT) has become a standard imaging technique for predicting prognosis in multiple myeloma (MM), but have potential inaccuracies in patients with renal impairment (RI).Aims:In this study, we investigated the prognostic role of 18F‐FDG PET/CT in patients with MM presenting with RI.Methods:Retrospective data for 74 patients with MM and RI between March 2012 and March 2017 were analyzed. Renal function was assessed using the estimated glomerular filtration rate (eGFR), which was calculated by the simplified Modification of Diet in Renal Disease (MDRD) formula. RI was defined as an eGFR of <60 mL/min/1.73 m2 at initial diagnosis. Severe RI was defined as eGFR <30 mL/min/1.73 m2. 18F‐FDG PET/CT was performed prior to induction therapy and PET/CT positivity was defined as the presence of more than three focal lesion (FL) or the presence of extramedullary disease (EMD).Results:A total of 29 patients (39.2%) had more than three FLs and 12 (16.2%) had EMD on baseline 18F‐FDG PET/CT. Thirty patients (40.5%) demonstrated PET/CT positivity. The median eGFR was 37.9 mL/min (range 3.0–59.8) and 24 (32.4%) had severe RI at initial diagnosis. Over the median follow‐up duration of 37.5 months, 54 patients (73.0%) had progressed and 22 (29.7%) had died by the time of the last follow‐up visit. The median progression free survival (PFS) was 24.2 months (95% CI, 17.4–31.1) and the median overall survival (OS) was 68.3 months (95% CI, 44.1–92.5). Patients with PET/CT positivity had significantly inferior survival outcomes than those with PET/CT negativity (PFS, 12.7 months vs. 34.0 months, P < 0.001; OS, 42.5 months vs. not reached, P = 0.012). In patients with severe RI, PET/CT positivity was significantly associated with poorer PFS and OS (PFS, 12.7 months vs 34.4 months, P = 0.011; OS, 42.4 vs not reached, P = 0.081). By multivariate analyses, PET/CT positivity was independently prognostic factor for PFS and OS in total patients.Summary/Conclusion:18F‐FDG PET/CT may be useful imaging technique for predicting survival outcomes in patients with MM presenting with RI.image
PF665 SERUM FERRITIN LEVELS ARE INCREASED IN IDIOPATHIC ERYTHROCYTOSIS BUT REDUCED IN POLYCYTHEMIA VERA
Authors: Biagetti G. , Bertozzi I. , Cosi E. , Fabris F. , Randi M.L. 
Published: June 2019

Background:Absolute erythrocytosis is characterized by persistently raised Haemoglobin (Hb) and hematocrit (Ht) levels. The most studied form is Polycythemia Vera (PV), a clonal disease in which the proliferation of red cells is driven by mutations in JAK2. Secondary erythrocytosis are represented by rare congenital diseases, acquired forms, or idiopathic erythrocytosis (IE), a poorer studied disease in which the erythrocytosis has not a definite cause. Over‐production of red blood cells should drive a depletion of iron, and thus low serum ferritin levels. However, we often observe increased levels of ferritin at diagnosis in IE and we recently found that mutations or polymorphisms of HFE gene are commonly found in these patients.Aims:Could serum ferritin be an early help to hypothesize the cause of erythrocytosis in a patient? To answer this question, we retrospectively analysed levels of ferritin at diagnosis in PV and IE patients.Methods:We studied 72 patients with PV and 67 patients with IE, followed in our department. In each patient we recorded ferritin at diagnosis out of phlebotomy treatment. Other causes of hypo‐ and hyper‐ ferritinemia were excluded. Ferritin normal levels were considered 20–300 μg/L in men and 15–200 μg/L in women. All patients with a diagnosis of PV carried JAK2V617F or JAK 2 exon 12 mutation, while none of the patients with IE carried JAK2 or EPOR, VHL, PHD2, HIF‐1 alpha genes mutations. Presence and absence of HFE mutations in IE patients, if known, were registered. Statistical analysis was performed using the Mann‐Whitney test, Fisher's exact test and the t Student test.Results:Results are shown in the Table I.In addition, HFE mutations had been searched in 26 (39%) IE patients, and 13 (50%) of them had at least a mutated allele.Summary/Conclusion:Our results show a dramatic difference between levels of ferritin at diagnosis in PV and IE: in fact, 22% of PV patients had reduced ferritin at diagnosis out of phlebotomies, while on the contrary 28% of IE patients had increased levels of ferritin. Then, serum ferritin at diagnosis could address the physician to the origin of erythrocytosis. In addition, nearly half of IE patients have been already studied for presence of HFE mutations, and half of them carry at least one HFE mutated allele. We believe that a large part of IE patients carries a genetic impairment of the iron metabolism that could drive an enhancement of iron production: this could explain why in the presence of erythrocytosis iron is more consumed in PV patients than in IE ones. Further studies are needed about the presence of iron metabolism impairments in IE patients and, on the other hand, possible overlays of JAK2 and HFE mutations in PV patients.image
PF699 LUSUTROMBOPAG IS A SAFE TREATMENT OPTION FOR THROMBOCYTOPENIA IN PATIENTS WITH CHRONIC LIVER DISEASE UNDERGOING A SCHEDULED INVASIVE PROCEDURE: POOLED SAFETY ANALYSIS FROM 3 STUDIES
Authors: Brown R.S. , Izumi N. , Kano T. , Ochiai T. , Kurosaki M. , Violi F. , Shrestha P. 
Published: June 2019

Background:Lusutrombopag is a thrombopoietin receptor agonist approved in Japan and US for improvement of thrombocytopenia, and in EU for severe thrombocytopenia, associated with chronic liver disease in patients undergoing planned invasive procedures. In an integrated analysis of 2 Phase 3 studies, lusutrombopag reduced the need for platelet transfusions compared to placebo.Aims:Treatment with thrombopoietin receptor agonists has been associated with an increased risk of thrombotic events in patients with chronic liver disease. Thus, a thorough safety assessment of new agents is critical. A pooled retrospective analysis of 3 clinical studies was performed to assess safety of lusutrombopag.Methods:Safety data from 3 double‐blind, randomized, placebo‐controlled studies in patients with chronic liver disease and thrombocytopenia undergoing a scheduled invasive procedure (Phase 2b: M0626 [Japan; JapicCTI‐121944], Phase 3: L‐PLUS 1 [Japan; JapicCTI‐132323] and L‐PLUS 2 [global; NCT02389621]) were pooled. Adults with platelet counts <50x109/L at baseline received lusutrombopag 3 mg or placebo for up to 7 days before a procedure scheduled 9–14 days after randomization. Platelet transfusion was given if the platelet count remained <50x109/L no more than 2 days prior to procedure. Adverse event data were collected from signing of informed consent until the end of the post‐treatment period or early termination.Results:The pooled safety population included 341 patients (n = 171, lusutrombopag; n = 170 placebo). Approximately 65% of patients in the lusutrombopag and placebo groups experienced an adverse event (Table). Thrombotic and thromboembolic adverse events occurred in 1.8% (3/171) of lusutrombopag patients (cardiac ventricular thrombosis, n = 1 [patient had prior history of cardiac ventricular thrombosis]; portal vein thrombosis, n = 2) and 2.4% (4/170) of placebo patients (mesenteric vein thrombosis, n = 2; portal vein thrombosis, n = 2). Overall, bleeding‐related adverse events occurred in less lusutrombopag vs placebo patients (15 [8.8%] vs 27 [15.9%]), respectively. The 3 adverse events leading to death were not considered treatment‐related but due to the progression of underlying disease.Summary/Conclusion:In this pooled safety analysis, lusutrombopag was safe and well‐tolerated in patients with thrombocytopenia and chronic liver disease undergoing invasive procedures. Approximately 50% fewer bleeding‐related adverse events and no increased risk of thrombotic and thromboembolic adverse events were observed in patients treated with lusutrombopag vs placebo.image
PF706 OCCULT BLEEDING IN CHILDREN WITH IMMUNE THROMBOCYTOPENIA: RELATION TO LABORATORY PARAMETERS &ITP HEALTH QUALITY OF LIFE
Authors: Tantawy A. , Elsherif N. , Aboulfotouh K. , Kenny M. 
Published: June 2019

Background:Occult hemorrhage can occur in any internal organ in ITP patients. Four sites of occult hemorrhage deserve special attention including microscopic hematuria, fecal occult blood, retinal hemorrhage, and silent intracranial hemorrhage.Aims:The aim of this study was to investigate for the frequency of subclinical bleeding in Egyptian children with ITP and its relation to different clinical and laboratory parameters of the disease including bleeding score and health quality of life.Methods:This cross sectional study included 40 ITP patients recruited from the Pediatric Hematology&Oncology unit, Children Hospital, Ain Shams University. Occult blood in stools and urine analysis, fundus examination, and non‐contrast brain MRI, for brain microbleed, were doneResults:The total number of patients with occult bleeds was eleven. Two patients had occult blood in stool, five had microscopic hematuria, one had retinal bleeds and three patients had brain microbleeds. Their mean age was 10.23 ± 4.18 and their mean initial bleeding score was 2.55 ± 0.82. Nine patients with occult bleeding were chronic, one persistent and one acute ITP patients. There was no significant differences between patients with occult bleeding and those without as regards the initial bleeding score, the platelet counts & hemoglobin level, as well as the mean platelet counts & mean hemoglobin level over the disease duration. Although the scoring of the effect on the parent's life, Child and parents quality of life was low in 3 out of 11 patients with occult bleeding, we did not find a significant difference between patients with occult bleeding and those without as regards the ITP health quality of life itemsSummary/Conclusion:Our results suggest that subclinical bleeding is a potential risk in children with ITP, more commonly chronic ITP patients. We could not demonstrate a significant relation of occult bleeding to the laboratory findings, bleeding score, and the ITP health quality of life; nevertheless, the significance of the routine assessment of occult bleeding in ITP and the identification of high‐risk patients require additional studies.
PF739 SICKLE CELL DISEASE IN GERMANY IS HETEROGENEOUS AND RESULTS IN SEVERE MORBIDITY: ANALYSES FROM A NATIONAL REGISTRY
Authors: Kunz J. , Lobitz S. , Andrea J. , Regine G. , Cario H. , Oevermann L. , Hakimeh D. , Le Cornet L. , Beck D. , Karapanagiotou‐Schenkel I. , Tagliaferri L. , Kulozik A. 
Published: June 2019

Background:Sickle Cell Disease (SCD) in Germany exclusively affects immigrants and their descendants. Its increasing prevalence results in challenges for medical care for these patients.Aims:The registry aims at describing the epidemiology, clinical course and treatment of patients with SCD in Germany.Methods:To date, 367 patients have been included in the registry by 36 mainly pediatric institutions. At initial registration, basic data including date of birth, date and circumstances of diagnosis, genotype, country of origin, blood type and complications in the patient's history are reported. Annual follow‐ups document details on complications, laboratory parameters and treatment. Data of 327 patients were analyzed for this abstract.Results:Genotypes of registry patients were homozygous SCD in 75% of patients, HbSC disease in 12%, HbS/β0thal in 6% and HbS/β+thal in 7%. The main regions of origin were sub‐Saharan Africa (in total 69% of patients, including Ghana 19%, Nigeria 19%, Togo 9%) and the Middle East (in total 21%, including Lebanon 6%, Turkey 5%, Syria 4%). Although pilot projects for newborn screening for SCD were in place in some of the centers, only 35% of patients were diagnosed during their first year of life, 85% before the age of six. SCD was diagnosed on the occasion of presenting symptoms in 60% of patients. The mean age at registration was 12 years (median 10), with 10% of patients being older than 21 years at registration. The most frequent complications in the patients’ prior history were pain crises with hospitalization (67% of patients), acute chest syndrome (32%), splenic sequestration (15%), aplastic crisis (10%), stroke (4%) and sepsis (4%).During the first year of observation, 47% of the registry patients were hospitalized, 11% required treatment on an intensive care unit. Red blood cell transfusions were given to 27% of patients. 96% of patients with homozygous SCD or with HbS/β0thal at an age of 2 years or older were prescribed hydroxycarbamide, 76% of these patients under the age of 18 were annually examined by transcranial Doppler ultrasound (TCD).Summary/Conclusion:Patients with SCD in Germany are genetically and ethnically highly heterogeneous and suffer from severe morbidity. The diagnosis is frequently made too late because of the lack of a routine newborn screening for SCD. While the high rate of hydroxycarbamide prescription indicates good care at the institutions that contribute to the registry, the insufficient proportion of patients receiving routine TCD checks indicates an incomplete availability of the diagnostic infrastructure required for the optimal care of this challenging group of patients.