Pts Age Research Articles

Phase 1b Results for Subcutaneous Talquetamab Plus Daratumumab in Patients with Relapsed/Refractory Multiple Myeloma

Phase 1b Results for Subcutaneous Talquetamab Plus Daratumumab in Patients with Relapsed/Refractory Multiple Myeloma

Association between BCL2, BCL2 E17, MCL1 and BAX Protein Expression, Bone Marrow Microenvironment Histological Features, Clinical Presentation, Therapeutic Outcome, and the Overall Survival in Newly Diagnosed Multiple Myeloma

Association between BCL2, BCL2 E17, MCL1 and BAX Protein Expression, Bone Marrow Microenvironment Histological Features, Clinical Presentation, Therapeutic Outcome, and the Overall Survival in Newly Diagnosed Multiple Myeloma

Prophylaxis of Neutropenia with Mecapegfilgrastim in Patients with Hematologic Malignancies

Background: Neutropenia is a frequently reported adverse event in patients with hematologic malignancies. Prophylactic administration of long-acting granulocyte colony stimulating factor(G-CSF) had been widely applied in different solid tumors. However, the effect of long-acting G-CSF in patients with hematologic malignancies was not well studied.Methods: A multi-center, non-interventional study was conducted to explore the efficacy and safety of mecapegfilgrastim, a long-acting G-CSF, in patients with hematologic malignancies. Patients administered at least twice mecapegfilgrastim were included for statistical analysis. The baseline characteristics, effectiveness and safety results were presented.Results: Mecapegfilgrastim were administrated prophylactically in 74 patients (pts) with hematologic malignancies (Diffuse large B-cell lymphoma 34 pts, follicular lymphoma 9 pts, peripheral T-cell lymphoma 3 pts, primary mediastinal large B-cell lymphoma 3 pts, angioimmunoblastic T-cell lymphoma 3 pts, Anaplastic Large Cell Lymphoma 3 pts, classic Hodgkin's lymphoma 3 pts, other lymphomas 12 pts, other hematologic malignancies 4 pts). The median age of pts was 58 years. The ECOG performance score were 0 -2. Common chemotherapy regimens were CHOP, CHOEP, DHAP and GemOx. Rituximab, anti-PD-1 antibody, BTK inhibitors, chidamide and lenalidomide were the most administrated targeted or immunotherapeutic agents. In all 250 treatment cycles (61 chemotherapy cycles and 189 immunochemotherapy), twenty-seven pts had grade ≥3 neutropenia in 41 (16.4 %) cycles, fifteen pts had grade 4 neutropenia in 22(8.8 %) cycles, four pts experienced febrile neutropenia in 4 (1.6 %) cycles. In 61 chemo-alone treatment cycles, grade 3/4 neutropenia was reported in 10(16.4%) and, 4 (4.9 %) cycles, febrile neutropenia was recorded in 2(3.3 %) cycles. During 189 cycles of immunochemotherapy treatment, grade 3/4 neutropenia and febrile neutropenia was observed in 31(16.4%), 18(9.5 %) and 2(1.1 %) cycles, respectively. There were 5 cycles of grade 4 neutropenia occurred in 9 lenalidomide contained treatment cycles, and febrile neutropenia was reported in 1 cycle.Grade ≥ 3 neutropenia induced treatment delay (≥ 7 days) was reported in 12 cycles while dose of cytotoxic drugs were not decreased. Eleven pts developed infection including 6 pneumonia events, they were treated with antibiotics in 23 cycles. Adverse event (AE) was reported in 64(86.6 %) pts. Fourteen (18.9 %) pts were hospitalized due to AEs. Most common grade 1/2 AEs related to mecapegfilgrastim were leucocytosis (18.9%) and neutrocytosis (6.8 %).Conclusion: Mecapegfilgrastim showed promising effectiveness and reliable safety profile in pts with hematologic malignancies. Further investigation is warranted. DisclosuresNo relevant conflicts of interest to declare.

Initial Safety and Efficacy Results from the Phase II, Multicenter, Open-Label Solace-Kids Trial of Crizanlizumab in Adolescents with Sickle Cell Disease (SCD)

Initial Safety and Efficacy Results from the Phase II, Multicenter, Open-Label Solace-Kids Trial of Crizanlizumab in Adolescents with Sickle Cell Disease (SCD)

A Multi-Institution Analysis of Relapsed Lymphoma Occurring during Pregnancy Including Pharmacokinetics with Antenatal Checkpoint Inhibitor Therapy

Introduction: Lymphoma (LYM) diagnosed during pregnancy is an uncommon occurrence. There are significant ethical and management challenges that involve maternal and fetal risks associated with delayed intervention vs antenatal therapy. Moreover, there are a scarcity of available data regarding relapsed/refractory LYM occurring during pregnancy, which may guide practitioners and patients (pts) on treatment options, prognosis, maternal complications, and fetal outcomes.Methods: We performed a detailed retrospective analysis of pts diagnosed with relapsed LYM during pregnancy 1989-2021 across 10 academic centers worldwide. Data on disease characteristics, treatment, obstetric complications and fetal outcomes were examined. Survival analyses were performed using Kaplan-Meier. In addition, via an IRB approved protocol for a pt receiving antenatal checkpoint inhibitor therapy, we analyzed blood during gestation for measurement of nivolumab (NIVO) concentrations for comparison of pt serum concentrations to expected/predicted, as well as cord blood, and placenta concentrations for NIVO. All aliquots were run on a CLIA-level certified and validated ELISA assay (range 10-250 ng/mL, with dilutions up to 1000-fold [250 ug/mL]).Results: Overall, 23 cases of relapsed LYM during gestation were identified. 18 (78%) pts had Hodgkin LYM (HL), 2 (9%) peripheral T-cell LYM, and 1 pt each diffuse large B-cell LYM, follicular LYM, and marginal zone LYM. The median age of pts at time of relapse during pregnancy was 31 years (21-35). The median time from initial LYM diagnosis to pregnancy relapse was 24 months (7-229). Overall, 19 (82%) pts were White and there was 1 each Hispanic, Black, American Indian, and Asian. At time of relapse, 3 (13%) pts had stage I, 10 (44%) stage II, 4 (17%) stage III, and 4 (17%) stage IV disease; 12 (52%) pts presented with B-symptoms. Therapy was deferred to post-partum in the majority of pts; however, 5 (22%) pts received antenatal therapy (due to tumor burden, etc) between 20-32 weeks' gestation (Table). Among these, 4 achieved a complete response (CR), with 1 pt who had antenatal progressive disease (PD) requiring change to NIVO as detailed below.This 31-year-old female presented at 13 weeks' gestation with biopsy-proven relapsed HL (6 ABVD cycles 3 years prior). By 18 weeks, her ECOG PS was 3, and she developed bulky pelvic adenopathy >10cm, and severe hypercalcemia, hyponatremia, and progressive non-hemolytic anemia (5.4 gm/dL). Modified ESHAP was started at week 19 with brisk subjective improvement and resolution of lab abnormalities; however, she had PD at week 25. Single-agent NIVO was started after counseling about potential risks/benefits. She received 240 mg IV q 2 weeks for 6 cycles (through week 37) resulting in near CR, and she delivered a healthy full-term male at 38.2 weeks. A 30-day post-partum PET confirmed CR. In addition, maternal NIVO pharmacokinetic (PK) analyses showed levels were within normal ranges based on PK simulations (Figure 1). Cord blood concentration was 64% of the maternal exposure blood level, while there was no quantifiable NIVO detected in the placental tissue.Overall, 9 (39%) pts underwent transplantation post-partum (Table). With a median follow-up of 37 months for all pts, 3-year progression-free survival (PFS) and overall survival (OS) were 33% and 90%, respectively (Figure 2). Detailed maternal and fetal outcomes were available on 22 pts (Table). Of these, there were 18 lives births with the majority having vaginal delivery. The majority of pts had clinician-initiated late preterm deliveries with a median gestational age at delivery of 36 weeks (26-39). The median birthweight was 2777 grams (740-3900), and there were no reported malformations. For maternal complications, 1 pt each had preeclampsia, endometritis, and chorioamnionitis (all pts who deferred antenatal therapy).Conclusions: To the best of our knowledge, this is the largest cohort of pts diagnosed with relapsed LYM during pregnancy to date, including the first report of a LYM pt receiving antenatal checkpoint inhibitor immunotherapy. Treatment was deferred in the majority of pts, though it was well tolerated by those who received antenatal therapy. Furthermore, there were relatively few obstetrical or fetal complications. And despite modest PFS, OS was robust. Finally, use of antenatal NIVO in one relapsed HL pt was safe, effective, and associated with expectant maternal PKs. [Display omitted] DisclosuresAhmed: Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seagen: Research Funding; Merck: Research Funding; Xencor: Research Funding. Olszewski: TG Therapeutics: Research Funding; PrecisionBio: Research Funding; Celldex Therapeutics: Research Funding; Acrotech Pharma: Research Funding; Genentech, Inc.: Research Funding; Genmab: Research Funding. Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Farooq: Kite, a Gilead Company: Honoraria. Vose: Kite, a Gilead Company: Honoraria, Research Funding. OffLabel Disclosure:nivolumab used in 2nd-3rd trimester of pregnancy for a woman w/ Hodgkins lymphoma

Pooled Analysis of First-Line Treatment with Targeted Agents in Patients with Chronic Lymphocytic Leukemia (CLL) Aged 80 Years and Older

Pooled Analysis of First-Line Treatment with Targeted Agents in Patients with Chronic Lymphocytic Leukemia (CLL) Aged 80 Years and Older

The Use of Ibrutinib in Italian CLL Patients Treated in a Real-World Setting (EVIDENCE): A Preliminary Report

IntroductionIbrutinib is the only once-daily Bruton's tyrosine kinase (BTK) inhibitor with significant survival benefit vs chemo- and /or immunotherapy in multiple phase 3 studies of patients (pts) with chronic lymphocytic leukemia (CLL). It has profoundly changed the treatment landscape of CLL with the longest follow-up. However, seven years (yrs) after ibrutinib was approved in Italy by regulatory agencies for CLL treatment, available data on the patterns of care of such pts in the setting of clinical practice is limited.Herein we present the first interim analysis (IA) of EVIdeNCE (ClinicalTrials.gov Identifier: NCT03720561), a multicenter, observational clinical study designed to describe the current management of pts receiving ibrutinib in real-world setting in Italy in terms of retention rate: the study's primary end point.MethodsEVIDENCE 312 treatment-naïve (TN) 38% and relapsed/refractory (R/R) 62% pts with CLL according to the iwCLL diagnosis criteria observed at 39 Italian hematological institutions in the period between November 2018 and October 2019. Inclusion criteria were treatment with ibrutinib according to the European Summary of Product Characteristics as per routine clinical practice started within the previous 3 months. The purpose of this IA is to provide demographics and disease characteristics at baseline and a preliminary evaluation of ibrutinib retention rate after one year of follow-up, along with its safety profile.ResultsThe median age of pts at the time of ibrutinib initiation was 71.0 yrs (range 41.0-89.0), with 60% ≥70 yrs, 63.2% male, and 90% with Eastern Cooperative Oncology Group (ECOG) performance 0-1. Baseline Rai stage 0-I, II, and III-IV accounted for 18.3%, 29.7% and 52.1% pts, respectively. Patients in stage IV were observed in 40% of the R/R and 27% in TN subgroup. Considering 120 pts with known mutational status, del(17p) and/or TP53 mutation were present in 50.0% of pts (TN=52.1%, R/R=48.6%), while IGHV was unmutated in 35.0% (TN=33.3% and R/R=36.15) and mutated in 15.0% (TN=14.6%, R/R=15.3%). At baseline, 62.9% of pts had comorbidities and 30.6% presented with a history of cardiovascular diseases (CVDs). A CIRS score ≥6 was observed in 28.5% of pts. The median time from CLL diagnosis to the start of ibrutinib was 5.1 yrs (TN 1.75 yrs vs R/R 7.27 yrs).At least 1 treatment-emergent adverse event (TEAE) of any grade was experienced by 70.7% of pts. Frequencies were as follows: infections (30.8%; COVID-19 infections 3.2%), arthralgia (10.8%), neutropenia (9.3%), fatigue (8.4%), diarrhea (7.7%), atrial fibrillation (7.4%; grade 3-4, 4.2%), fever (7.1%), rash (6.4%), anemia (6.1%) and hypertension (4.2%). Mild bleeding TEAEs were reported in 16.1% of pts with no major bleeding event. TEAEs were more frequent in the elderly (≥65 yrs) while no significant differences in the rate of TEAEs were recorded in TN and R/R pts (69.7% vs 71.4%, respectively). Serious TEAEs were reported in 21.9% of pts.Overall in intention to treat (ITT), 32 deaths (10%) were observed (TN=8, R/R=24). The most common causes of death were infections (3.5%) and progressive disease (PD) (1.9%).Permanent discontinuation was observed in 56 (18%) of the pts (TN=17.2%, R/R=18.7%) and it mostly occurred within the first 6 months. Main causes of discontinuation were toxicity (6.1%), PD (3.8%) or death (3.5%). Temporary interruptions (≤ 3 months without therapy and/or dose modifications) during the whole observation period occurred in 30.3% (TN=35.3%, R/R=27.2%) and 37.7% (TN=37.5%, R/R=37.8%) of pts, respectively, mainly determined by toxicity and clinical judgment.Finally, in this first IA after 17.3 months (range 1.1 - 27.0) median follow-up, the ibrutinib retention rate (calculated as the ratio between the number of patients who retained ibrutinib treatment over the total number of patients at risk) at 1-year was 81.9% [95% confidence interval (CI), 77.2% - 86.1%] with no difference between TN 83.2% (95% CI, 75.2% - 89.4%) and R/R 81.2% pts (95% CI, 74.9% - 86.4%).ConclusionsEVIDENCE is the first real-world study of ibrutinib use in CLL clinical practice in Italy. Ibrutinib retention rate at one-year suggests a better knowledge and expertise of hematologists in the management of ibrutinib-related toxicities that may result in an improved long-term outcome of pts with CLL. DisclosuresMolica: Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Astrazeneca: Honoraria. Scarfo: Astra Zeneca: Honoraria; Abbvie: Honoraria; Janssen: Honoraria, Other: Travel grants. Murru: Abbvie: Consultancy, Honoraria, Other: travel and accommodation; Janssen: Consultancy, Honoraria. Sportoletti: AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Frigeri: Celgene: Consultancy, Speakers Bureau; Abbvie: Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Amgen: Speakers Bureau. Sanna: Janssen: Consultancy; Abbvie: Consultancy; Astra Zeneca: Consultancy. Coscia: Janssen: Honoraria, Other, Research Funding; AbbVie: Honoraria, Other; AstraZeneca: Honoraria; Gilead: Honoraria. Reda: Abbvie: Consultancy; Astra Zeneca: Consultancy; Beigene: Consultancy; Janssen: Consultancy. Tafuri: Novartis: Research Funding; Roche: Research Funding; Celgene: Research Funding. Grugnetti: Janssen: Current Employment. Magarotto: Janssen: Current Employment. Mauro: Tskeda: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria, Speakers Bureau.

Simulation Free Radiotherapy: An Emerging Form of Simulation and Treatment Planning to Simplify Palliative Radiotherapy

<h3>Purpose/Objective(s)</h3> Simulation free RT (SF-RT) is an emerging technique in which a patient's (pts) diagnostic imaging is used for simulation (sim) and treatment planning. SF-RT may increase the speed of treatment planning while reducing pt visits. In palliative care, minimizing time in the radiation oncology (RO) department and expediting treatment is critical. We evaluated clinical data for pts treated with palliative SF-RT compared to pts treated with palliative CT sim RT (CT-RT) in a retrospective matched cohort analysis. <h3>Materials/Methods</h3> From 1/2020 to 11/2020, 30 sessions of palliative SF-RT were performed at a single institution. A session was defined as a single course of palliative RT. Pts received both single and multi-fraction regimens. Time points collected included time of order approval, plan approval, and first treatment. A matched cohort of pts treated with palliative CT-RT was acquired via Reweight Mahalanobis Distance Matching matched on age, total dose, and treatment site. Descriptive statistics were calculated on all variables and statistical significance was evaluated using the Chi-square method for categorical variables and the t-test method for continuous variables. <h3>Results</h3> 30 sessions of palliative SF-RT were matched with 30 sessions of palliative CT-RT, with the median distance matching being 0.073 (0.018-0.147). Median age of pts treated with SF-RT was 61 (56-73) and median age of pts treated with CT-RT was 62 (55-72). The majority of pts in both groups were treated on an outpatient basis. The most common site treated in both groups was spine. 70% of SF-RT sessions were single fraction, and 57% of CT-RT sessions were single fraction. Mean time from order approved to plan approved was 1.8 days (d) (+/- 1.8 d) for SF-RT sessions and 3.0 d (+/- 3.4 d) for CT-RT sessions. Mean time from plan approved to first treatment was 2.3 d (+/- 2.8 d) for SF-RT sessions and 2.0 d (+/- 2 d) for CT-RT sessions. Mean time from order approved to first treatment was 4.1 d (+/- 3.3 d) for SF-RT and 5.0 d (+/- 3.8 d) for CT-RT. There were no statistically significant differences between variables. <h3>Conclusion</h3> SF-RT led to an average of .9 d faster time from order approval to first treatment while requiring one less patient visit to the RO department when compared to CT-RT. These data demonstrate the potential for SF-RT to increase the efficiency of palliative RT while reducing pt visits to the RO department.

Outcome of 5-years active cardiological management of oncohematological patients on targeted therapy

Abstract Background The overall survival of oncohematological patients (pts) depends not only on the severity of the cancer, the anticancer therapy used and the comorbidity of the pts. The most important role in the management of these pts is played by the supervision of a cardiologist. Purpose To assess the effect of active cardiac management on the overall survival of oncohematological pts on targeted therapy with ibrutinib. Methods We examined and observed in dynamics for 5 years 217 pts with chronic lymphocytic leukemia (CLL), constantly receiving ibrutinib, inducing arterial hypertension (AH) and atrial fibrillation (AF) in a part of the pts. All pts underwent echocardiography (Echo), 24-hour Holter ECG monitoring (HM), assessment of comorbidity using the Charlson index and screening of fragility using the G8 questionnaire. Everyday measurement of blood pressure, heart rate in the morning and in the evening with keeping a measurement diary was recommended for all pts, but 89 pts were performed, who constantly contacted us remotely using instant messengers and formed an active cardiac management (ACM) group. Results We studied the overall survival of pts with CLL receiving targeted therapy with ibrutinib, depending on cardiac monitoring, starting from the first visit. The age of pts in the ACM group (n=89) and in other pts (n=138) did not differ and amounted to 66.0 (60.0–70.0) years and 66.0 (59.0–74.0) years respectively. The number of men and women in the groups was comparable. In the ACM group, there were significantly more pts with AH - 86.5% and with AF - 42.7% compared to 50.4% with AH and 15.9% with AF in the rest of the pts (p&amp;lt;0.0001 in both cases) and a comparable number of pts with coronary artery disease. According to the screening HM, there were more pts with short AF episodes in the ACM group - 31.4% versus 8.0% in the rest of the pts (p&amp;lt;0.0001). Accordingly, the number of pts who received cardiological treatment in the ACM group was 87.6%, in the group of other pts - 53.6% (p&amp;lt;0.0001). Echo parameters did not differ in the groups. Indicators that significantly affect survival in the general group (Charlson index, scores of the G8 questionnaire) did not differ significantly in the ACM group and in other pts with CLL. The groups also did not differ in hematological status and the number of cases of second tumors. At the same time, despite a significantly more pronounced cardiac comorbidity, oncohematological pts under active cardiac monitoring, including continuous remote monitoring, demonstrated better survival compared to other pts (p&amp;lt;0.0001). Conclusions Conducting active cardiac management, including constant remote observation, allows achieving higher overall survival rates of hematological cancer patients, despite a more severe cardiac status compared to other pts under periodic supervision of a cardiologist. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): no founding sources

Treatment patterns in patients with Familial hypercholesterolemia: evidence from real-world studies in Germany and the UK

Abstract Background Familial hypercholesterolemia (FH) includes a spectrum of disease as per the number and effect of mutations in specific proteins involved in low-density lipoprotein cholesterol (LDL-C) metabolism, together with other genetic factors. Elevated LDL-C levels have been strongly associated with risk of cardiovascular and coronary heart disease, with up to 10-fold risk in patients (pts) with FH than without FH. The aim of lipid-lowering treatments (LLTs) is to reduce the LDL-C levels, although there is limited research describing treatment patterns and LDL-C outcomes in FH pts in routine care. Purpose To characterize the treatment patterns and LDL-C outcomes of FH pts in the real-world setting in Germany (GER) and the UK. Methods We conducted two descriptive, non-interventional and retrospective cohort studies. Pts in GER were identified from General Physician (GP) and Cardiology practices available in electronic medical records database Disease Analyzer (January 1992-June 2020). Pts in the UK were identified from the Clinical Practice Research Datalink linked to the Hospital Episode Statistics admitted pts care and Office of National Statistics datasets. Pts were included if they had diagnosis of FH (index date [ID]) and data available within 6-month before and 3-month after the ID. The first diagnosis of FH in the identification period (GER, 1/07/2015–30/06/2019; UK, 01/01/2010–31/05/2018) was considered the ID. Persistence and adherence to the recorded LLT at ID was analyzed for pts with at least 12 months and 24 months of follow-up. Persistence was measured as the duration (in days) with allowed gap of 60 days and adherence as proportion of days covered (PDC). Results Analysis included 2,105 FH pts from GER and 9,846 from the UK. Data are presented as GER/UK. The mean (SD) age of pts was 60 (15)/52 (14) years, and 60%/61% were females. Hypertension (53%/27%) and depression (31%/38%) were the common comorbidities. At ID, statin monotherapy (29%/68%) was the most commonly prescribed LLT. The use of ezetimibe, fibrates and PCSK9 inhibitors was very low in both countries (Table 1). Of note, LDL-C measurements at ID (−6m/+3m) were available for 31%/73% of pts. In pts with uncontrolled LDL-C (≥55 mg/dL), 34%/64% were receiving statin monotherapy, whereas there was no use of LLT in 62%/29% of pts. During the 24 months follow-up, the mean (SD) persistence and PDC to statins monotherapy was 471 (264)/489 (289) days and 0.65 (0.36)/0.69 (0.46), respectively, with 50%/70% of pts being adherent (PDC ≥0.80). Conclusions In our study, in GER, the rate of LDL-C measurements was low. In both GER and UK, almost all measured patients had LDL-C ≥55mg/dL at ID. Findings indicate low prescriptions of LLTs in GP setting, particularly non-statin LLTs in both countries. The mean adherence (PDC) in GER and the UK was 65% and 69%, respectively within 24 months after ID. Improved LDL-C monitoring and new therapies with potential to lower LDL-C are warranted. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novartis Pharma AG, Basel, Switzerland

P40.14 Efficacy and Safety of Endostar Combined With Camrelizumab and Chemotherapy in Treatment of Advanced NSCLC: A Multi-Center Retrospective Study

Both Recombinant human endostatin (Endostar) and Camrelizumab have been approved in combination with chemotherapy in treatment of NSCLC in China. This study aims to observe the efficacy and safety of endostar plus Camrelizumab and chemotherapy in treatment of advanced NSCLC. This is periodic result. This is a multi-center, retrospective study. Advanced NSCLC patients (pts) who received endostar plus Camrelizumab and chemotherapy at least 2 courses were collected from December 2019. After two courses, the follow-up therapy will be decided by investigators. Baseline characteristics, efficacy evaluation and safety data were analyzed. Tumor response was evaluated according to RECIST 1.1. Adverse events (AEs) were graded according to NCI-CTC AE 4.0. The primary endpoint was progress-free survival (PFS), overall response rate (ORR), duration of response (DOR), overall survival (OS) and safety were included among secondary endpoint. Untill Mar. 2021, 21 pts were enrolled, and 17 pts were analyzed. The median age of pts was 55 years. 71% was male, 90% was diagnosed at stage IV. 76% was adenocarcinoma and 19% was squamous cell carcinoma. 67% received endostar combined with Camrelizumab and chemotherapy as first-line. The ORR and DCR is 71% and 100% respectively, with one CR patient. The treatment of 52% (11) pts is ongoing and the median PFS was not reach. In the safety-evaluable population, the most common AEs is thrombocytopenia (24%，>3 grade 10%), nausea and vomiting(24%，>3 grade 5%) and liver damage (19%). One pt was considered as immune-related hepatitis. Reactive cutaneous capillary endothelial proliferation (RCCEP) caused by Camrelizumab is 10% and none in >3 grade AEs.View Large Image Figure ViewerDownload Hi-res image Download (PPT) This retrospective study showed a promising efficacy and a good tolerance in advanced NSCLC pts with Endostar plus Camrelizumab and chemotherapy. This combined treatment maybe a new choice and we look forward to prospective study in furture.

Abstract 2195: Differential transcriptomic profiling of primary tumors and metastatic sites in advanced prostate cancer

Abstract Understanding the distinct genetic features of the primary tumor and metastases in advanced prostate cancer (PCa) has clinical relevance and potential therapeutic implications. Studies utilizing differential gene expression analysis between primary tumors and sites of metastases continue to characterize the evolution of PCa from castration-sensitive (CSPC) through metastatic castration-resistant PCa (CRPC). This study aimed to investigate the genomic features of a cohort of patients (pts) with PCa with primary and/or metastatic tumors submitted for genomic analysis. We hypothesize that unique genomic features are associated with the site of metastases and can reveal potential site-specific drivers of disease progression as well as therapeutic targets. We performed a retrospective analysis of tumor biopsies by next-generation sequencing (NGS) from 45 patients with PCa. Targeted DNA sequencing of more than 500 cancer-associated genes was performed in paraffin-embedded tumor samples. All 45 tumors [(primary tumors (17), metastatic sites (28)] had DNA sequencing data available. Among these, 22 were additionally subjected to transcriptome profiling by RNA-seq. This subset comprised: 8 prostate and 14 metastatic samples [lymph node (7), bone (3), and visceral (4)]. Visceral sites included liver (1), colon (1), stomach (1), and bladder (1). The median age of pts was 66 years (range 50-84). The median prostate-specific antigen (PSA) level at diagnosis was 65 ng/mL (range 0.5-3,403). Among the 24 pts with Gleason score available, 17 (70%) had grade group 5 (3 - Gleason 10; 14 - Gleason 9). Primary tumors analyzed by NGS included CSPC (12) and CRPC (6). Most metastatic tumors were CSPC at biopsy (15 - CSPS; 12 - CRPC). Among the cohort, frequent gene alterations affected homologous repair deficiency genes (29.6%), as well as PTEN (20.3%) TMPRSS2 (25.9%), and FOXA1 (5%) genes. Differential gene expression and pathway analysis of RNA-seq data was performed using Bioconductor on the R statistical computing environment. Comparisons between primary and metastatic gene expression profiles revealed shared features among sample groups, including transcriptional changes to interferon-alpha and -gamma, cell cycle regulators and Myc targets, whereas others were distinct to the sites of metastasis. Bone metastases exhibited regulatory changes to JAK/STAT signaling and angiogenesis, as well as alterations in DNA repair. Visceral tumor samples were the most diverse cohort in terms of global transcriptome state, but were notable for MTOR and androgen signaling. Lymph node biopsies showed pronounced TNF-α signaling via NFkB and oxidative phosphorylation. Our results exemplify the cellular and molecular diversity between primary tumors and metastatic sites and highlight potential pathways and transcriptome profiles unique sites of metastases. Additional analysis on expanded cohorts of pts is ongoing. Citation Format: Luke B. Soliman, Andre L. De Souza, Praveen Srinivasan, Matthew Danish, Dragan J. Golijanin, Ali Amin, Anthony E. Mega, Wafik S. El-Deiry, Paul Bertone, Benedito A. Carneiro. Differential transcriptomic profiling of primary tumors and metastatic sites in advanced prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2195.

Efficacy and Safety of Subcutaneous or Intravenous Administration of Rituximab in Patients with CD20+ Diffuse Large B-Cell Lymphoma or Follicular Lymphoma: Final Results of the Randomized, Open-Label, Crossover, PrefMab Study

Introduction: Rituximab (R) plus chemotherapy (chemo) is standard of care for patients (pts) with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). A subcutaneous (SC) formulation of R (R-SC) that has a non-inferior pharmacokinetic profile to the intravenous (IV) formulation (R-IV) and similar efficacy and safety in DLBCL and FL pts is now available for clinical use. The randomized, open-label, crossover, Phase 3b PrefMab study (NCT01724021) aimed to explore pt preference and treatment satisfaction for the SC vs IV formulation of R. In the primary analysis (data cut-off, January 19, 2015; Rummel et al. Ann Oncol 2017), a strong pt preference for R-SC over R-IV administration was demonstrated (81% vs 11% at Cycle 8; primary endpoint). In addition, on the Rituximab Administration Satisfaction Questionnaire, median scores were higher for R-SC vs R-IV for ‘Impact on Activities of Daily Living’, ‘Convenience of Therapy’, ‘Satisfaction with Therapy’, and ‘Psychological Impact’. No new safety signals were reported. Here, we present the final analysis of the PrefMab study, which was performed after all pts had completed at least 24 months' follow-up (data cut-off, December 20, 2016) with a focus on long-term pt outcomes and safety.Methods: Pts aged 18-80 yrs with previously untreated CD20+ DLBCL or FL were randomized 1:1 to receive one of two 8-cycle schedules of R in combination with 6-8 cycles of chemo (CHOP, CVP, or bendamustine, as per local practice): Sequence A (n=372), 1 cycle R-IV (375mg/m2) then 3 cycles R-SC (1400mg) then 4 cycles R-IV; Sequence B (n=371), 4 cycles R-IV then 4 cycles R-SC. Maintenance therapy was not mandated by the study protocol; however, pts with FL could receive maintenance at the investigator's discretion. Secondary endpoints reported here include overall (OR) and complete response (CR) rates (assessed according to Cheson 1999 criteria) and investigator-assessed progression-free (PFS), event-free (EFS), disease-free, and overall survival. Safety was also assessed by treatment-emergent adverse event (AE) reporting. Efficacy was analyzed in all randomized pts, safety in all pts who received ≥1 dose of R.Results: Of 743 randomized pts, 740 received study treatment (465 pts with DLBCL [63%], 273 with FL [37%], and 2 other [0.3%]). Demographics and baseline characteristics are presented in Table 1. The median age of pts with DLBCL was 61 yrs and of pts with FL was 59 yrs. The majority of pts with DLBCL and FL received CHOP chemo (Table 1). OR rates were >90% in both DLBCL and FL pts (Table 2). CR rates were 55.1% in pts with DLBCL and 44.4% in pts with FL (Table 2). PFS rates at 3 yrs were 79% in DLBCL pts and 91% in FL pts. Other time-to-event endpoints are presented in Table 2. EFS was shorter in FL pts than DLBCL pts; however, because R maintenance was considered a non-protocol-specified anti-lymphoma therapy, FL pts were censored at the time of starting maintenance therapy. Treatment sequence had no impact on response rates or time-to-event endpoints. Pharmacokinetic serum-level data will be presented.Of pts who received ≥2 cycles of treatment, 653/712 (92%) experienced ≥1 AE on or after Cycle 2. AEs were generally balanced according to administration route and diagnosis, although a higher rate of grade ≥3 AEs and serious AEs occurred in DLBCL pts compared with FL (Table 3). Most AEs occurred in Cycle 1, during which all pts received R-IV (pts with AE in Cycle 1: Arm A, 71%; Arm B, 69%). No administration-related reactions (ARRs) occurred at a frequency of ≥2% in pts receivingR-SC or R-IV on or after Cycle 2. There were no differences in rates of ARRs according to IV or SC administration. FL pts were more likely to experience an ARR than DLBCL pts. At the end of the study, 104 pts had died (85 DLBCL; 19 FL). Fatal AEs related to R, according to the investigator's judgment, included oropharyngeal candidiasis, pneumonia, septic shock, febrile neutropenia, and myocardial infarction (1 case each).Conclusions: In addition to the strong pt preference for SC dosing and improved satisfaction observed in the primary analysis, these findings confirm that R-SC is an efficacious and well-tolerated treatment option in DLBCL and FL pts. Overall, outcomes did not appear to be impacted by treatment sequence. [Display omitted] DisclosuresRummel:Roche: Honoraria, Other: PrefMab is sponsored by F. Hoffmann-La Roche Ltd. Third-party Medical Writing assistance, under the direction of Mathias Rummel, was provided by Lynda McEvoy of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd, Research Funding. Brugger:AstraZeneca: Employment, Equity Ownership. Re:Gilead: Membership on an entity's Board of Directors or advisory committees. Task:Genentech: Employment, Equity Ownership. McIntyre:Roche: Employment, Equity Ownership. Meier:Roche: Employment. Osborne:Roche: Employment. Smith:Roche: Employment. Grigg:Roche: Other: Funding to attend ASH 2016.

Cytogenetic and Molecular Responses after 2 Years of Tyrosine Kinase Inhibitor (TKI) Treatment in Simplicity, an Observational Study of Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Patients (Pts) in Routine Clinical Practice

Abstract Introduction: Data on clinical response and factors associated with response in CP-CML outside clinical trials are limited.SIMPLICITY (NCT01244750) is an ongoing observational study of CP-CML pts in routine clinical practice receiving first-line (1L) imatinib (IM), dasatinib (DAS) or nilotinib (NIL) in the US and Europe. This analysis aims to describe the factors associated with achievement of complete CyR (CCyR) and major MR (MMR). Methods: Clinical response after start of 1L TKI was assessed by CyR (karyotype or FISH) and MR (only tests by PCR on the international scale were included) as determined by the treating physician. Proportions of patients achieving CCyR and MMR between 30 days and either 12 or 24 months (mos) are presented; data at specified time points will be provided at presentation. Logistic regression models were used to identify factors associated with CCyR and MMR by 12 and 24 mos after 1L TKI initiation. Results: By March 03 2017, 1242 pts were enrolled prospectively in SIMPLICITY, receiving IM (n=416), DAS (n=418) or NIL (n=408); 55% were male. The median (interquartile range; min-max) age of pts at initiation of 1L TKI was 57 (46-68; 18-91) years; 35% of pts were treated in Europe, 65% in the US; 53% at academic centers and 47% at community practices. Numbers of pts followed by 3, 6, 12 and 24 months were 1233, 1224, 1195 and 1121, respectively. Of pts followed 12% (n=151), 31% (n=384), 44% (n=522) and 51% (n=567) had documented CyR testing by 3, 6, 12 and 24 mos; 23% (n=285), 55% (n=672), 72% (n=857) and 84% (n=937) of pts had documented MR testing by 3, 6, 12 and 24 mos; and 7% (n=82), 19% (n=231), 32% (n=379) and 42% (n=475) of pts had documented testing by both CyR and MR by 3, 6, 12 and 24 mos. Proportions of pts remaining on their 1L TKI declined with duration of follow-up. Of pts with documented CyR testing, 93% (n=141), 93% (n=356), 89% (n=464) and 85% (n=484) had remained on their 1L TKI by 3, 6, 12 and 24 mos, respectively. Of pts with documented MR testing, 93% (n=266), 91% (n=610), 85% (n=728) and 78% (n=730) had remained on their 1L TKI by 3, 6, 12 and 24 mos, respectively. In this non-controlled study, proportions of pts achieving CCyR were similar for pts tested by 12 and by 24 mos. For both periods, the proportion of pts achieving CCyR was highest for pts on 1L DAS, lower for 1L NIL, and lowest for 1L IM. Proportions of pts achieving MMR were higher for pts tested by 24 mos than by 12 mos. For both periods, the proportion of pts achieving MMR was highest for pts on 1L NIL, lower for 1L DAS, and lowest for 1L IM. Proportions were lower when calculated among pts followed through the period but not necessarily tested (intention-to-treat). Multivariate logistic regression analysis identified factors associated with MMR or CCyR by 12 and 24 mos after 1L TKI initiation. Receiving a second-generation (2G) TKI (i.e. DAS or NIL) as 1L therapy was associated with CCyR by 12 mos (odds ratio [OR]=2.6; p Conclusions: Response monitoring observed in clinical practice is not aligned with ELN/NCCN guidelines, so outcomes for the full SIMPLICITY cohort may differ from presented data on monitored patients. The lack of correlation between a 2G TKI as 1L therapy and achievement of MMR is unexpected, but may result from switches to 2L TKI in IM suboptimal responders or from differences in testing patterns in the individual cohorts; the uncontrolled nature of this study may have also contributed. Early switching of TKI treatment (previously found to be driven by toxicity, not response, and often from IM to 2G TKI) was associated with achieving MMR or CCyR by 12 mos. Not switching TKI, potentially a marker of better tolerance and adherence, was associated with achieving MMR or CCyR by 12 mos and 24 mos. Download : Download high-res image (116KB) Download : Download full-size image Figure . Disclosures Cortes: Teva: Research Funding; ARIAD: Consultancy, Research Funding; Sun Pharma: Research Funding; ImmunoGen: Consultancy, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding. Goldberg: Bristol Myers Squibb: Research Funding, Speakers Bureau; Pfizer: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Jazz: Speakers Bureau; Ariad: Speakers Bureau; Celgene: Speakers Bureau; COTA: Employment, Equity Ownership. Hehlmann: Novartis: Research Funding; BMS: Consultancy. Mauro: Bristol-Myers Squibb: Consultancy. Zyczynski: Bristol-Myers Squibb: Employment. Sen: ICON Clinical Research: Employment. Foreman: ICON Clinical Research: Employment. Gajavelli: Bristol-Myers Squibb: Employment. Gambacorti-Passerini: BMS: Consultancy; Pfizer: Consultancy, Honoraria, Research Funding.

Is Quality of Life (QOL) Predictive for Clinical Response in Chronic Phase-Chronic Myeloid Leukemia (CP-CML) Patients Treated with Dasatinib?

Baseline or pretreatment quality of life (QoL) has been shown to be a prognostic indicator in different hematological malignancies. The data on prognostic significance of QoL in CML are limited. The aim of this study was to examine if baseline QoL is predictive for clinical response achievement in pts with chronic phase-chronic myeloid leukemia (CP-CML) who receive treatment with dasatinib as first or second line.Total of 111 pts with CP-CML who participated in the multicenter observational prospective real-world study were involved in the analysis. All the pts were treated with dasatinib (100 mg daily) as first or second line in a real-world hematological setting. Clinical responses were assessed according to international clinical recommendations. For QoL assessment all the patients filled out the RAND SF-36 questionnaire. QoL impairment grade was evaluated for each patient. To examine baseline QoL as predictor of clinical response achievement (complete cytogenetic response, CCyR; major molecular response, MMR) univariate logistic regression was used. Backward Wald multivariate logistic regression to determine significant predictors of CCyR and MMR achievement during 12 mos of dasatinib treatment was performed with the following variables - age, gender, ECOG PS, time since diagnosis, line of TKI treatment, percent of Ph+ metaphases at start of dasatinib and baseline QoL impairment.Out of 111 CP-CML pts 17 were TKI-naive, 23 - early switched to dasatinib after failure of imatinib treatment (median duration of imatinib treatment - 6 mos, range 1-8), 71 were imatinib-resistant or intolerant before second line treatment with dasatinib (median duration of imatinib treatment - 40 mos, range 4-121). The median age of pts was 48 y.o. (range 19-83), 52% of pts - males. Median of baseline percent of Ph+ metaphases was 95% (range 0-100, interquartile range 30.3-100); data were not available in 8% pts. At baseline 58% of patients exhibited no/mild QoL impairment (<25% QoL decrease from QoL population norm); 11% - moderate QoL impairment (25-50% QoL decrease from QoL population norm); 31% - severe/critical QoL impairment (>50% QoL decrease from QoL population norm). With a median follow-up of dasatinib treatment of 12 mos (range 1-13.8) the incidence of CCyR and MMR was 46%, median of achieving - 6 mos (2-12). Univariate logistic regression revealed that baseline QoL impairment grade is predictive for CCyR and MMR achievement (p<0.05). Multivariate logistic regression model showed that baseline QoL impairment grade, baseline percent of Ph+ metaphases and line of TKI treatment were significant predictors of CCyR and MMR achievement during dasatinib treatment. Neither age and gender, nor time since CP-CML diagnosis and ECOG PS were predictive for CCyR/MMR achievement (p>0.05). Our final model had a Nagelkerke R2 of 0.23 and correct classification rate of approximately 68% (p=0.001). The lower baseline percent of Ph+ metaphases, earlier start of dasatinib treatment and better baseline QoL predicted for the achievement of CCyR and MMR. Assuming similar percent of Ph+ metaphases and the same line of TKI treatment, pts with less baseline QoL impairment were 1.3 times (26%; 95% CI=13-43; p<0.05) more likely to achieve CCyR and MMR than pts with higher QoL impairment (QR=2.9, 95% CI=1.3-6.5; p<0.05).In summary, the outcome of CP-CML pts treated with dasatinib could be predicted depending of baseline QoL data. The results of real-world data confirm that CP-CML pts with pronounced baseline QoL impairment have significantly worse clinical outcomes of dasatinib treatment in terms of optimal clinical response achievement. Thus, QoL data may not only be helpful in evaluating treatment outcomes from patients' perspectives but may also, like clinical information, be prognostic or predictive for clinical response, thus helping clinicians in their routine clinical practice to reach better decisions on patient management or identify their needs and decide on possible additional interventions, such as referral for counseling or psychosocial help and support. DisclosuresIonova:BMS: Research Funding.

INFLUENCE OF ACTIVE CARDIOMONITORING ON THE OVERALL SURVIVAL OF PATIENTS WITH CHRONIC LYMPHOLEUKEMIA RECEIVING IBRUTINIB

Introduction: overall survival of patients (pts) with chronic lymphocytic leukemia (CLL) depends not only on the severity of the CLL, the anticancer therapy used and the comorbidity of pts. The most important role in the management of these pts is played by the supervision of a cardiologist. Methods: we examined and observed in dynamics for 5 years 217 pts with CLL, constantly receiving ibrutinib, which induces arterial hypertension (AH) and atrial fibrillation (AF) in a part of the pts. All pts underwent echocardiography (ECHO), 24-hour Holter ECG monitoring (HM), assessment of comorbidity using the Charlson index and screening of fragility using the G8 questionnaire. Daily measurement of blood pressure, heart rate in the morning and in the evening with keeping a diary of measurements, was recommended for all pts, but only 81 pts were performed, who constantly contacted us remotely using instant messengers and made up an active cardiac monitoring group. Correction of treatment was carried out in accordance with these data. Results: a study of the overall survival of patients with CLL receiving ibrutinib, depending on cardiac monitoring, was carried out, starting from the first visit. The age of pts in the active cardiac monitoring group (n = 81) and in the rest of pts (n = 136) did not differ and amounted to 66.0 (60.0-70.0) years and 66.0 (59.0-74.0) years respectively. The number of men and women in the groups was comparable. In the active cardiac monitoring group, there were significantly more pts with AH - 86.5% and with AF - 42.7% compared to 50.4% with AH and 15.9% with AF in the remaining pts (p < 0.0001 in both cases) and a comparable number of pts with coronary artery disease. According to screening HM, there were more pts with short episodes of AF in the active cardiac monitoring group - 31.4% versus 8.0% in the rest of the pts (p < 0.0001). Accordingly, the number of pts receiving cardiac treatment in the active cardiac monitoring group was 87.6%, the rest was 53.6% (p <0.0001). ECHO parameters did not differ in the groups. Indicators that significantly affect survival in the general group (Charlson index, scores of the G8 questionnaire) did not have significant differences in the active cardiac monitoring group and in other pts with CLL. The groups also did not differ in hematological status and the number of cases of second tumors. Despite a significantly more pronounced cardiac comorbidity, CLL pts under active cardiac monitoring, including continuous remote monitoring, demonstrated better survival compared to other patients (p <0.0001). Conclusions: carrying out active cardiac monitoring, including constant remote observation, allows achieving higher overall survival rates for CLL pts, despite the more severe cardiac status compared to other patients under the periodic supervision of a cardiologist. Keywords: Cancer Health Disparities No conflicts of interests pertinent to the abstract.

MO292MALIGNANT DISEASE IS MORE COMMON WITH DETERIORATING KIDNEY FUNCTION IN PATIENTS WITH MEMBRANOUS NEPHROPATHY

Abstract Background and Aims Membranous nephropathy (MN) can be associated with tumor and present a paraneoplastic condition. Recently, development of tumors during the course of follow up is more in focus. It is especially interested whether patient with MN are prone to tumors, or tumors are condition indipendent of membranous nephropathy or consequence of imunosupressive therapy (IS). Method Retrospective data of all adult patients diagnosed with MN from 1987 to 2017 at the Department of Nephrology of University Hospital Centre Zagreb were analysed. Medical data regarding antropometric measeures and preexsisting comorbid disease at presentation and during follow up were derived from medical records and hospital informatic system. Furthermore, data regarding kidney function were used, namely serum creatinine (SCr), proteinuria. Renal function was assessed using CKD-EPI equation. CKD stages, partial and complete remission were defined according to KDIGO guidelines. Results From 1987 till 2017 a total of 122 patients were diagnosed with MN. Eighty nine (72.9%) were treated with imunosupressive therapy. Most commonly prescribed initial therapy was combination of corticosteroids and cyclophosphamide (N=66; 74%). Three (0,02%) patients had history of tumor with median of 3y (min – max 1-4 y) before glomerular disease presentation, two solid tumor, adenocarcinoma pulmonum and carcinoma prostatae, and one condition after allogenic haematopoetic transplantation due to acute myeloid leukemia. There was no difference in clinical presentation between those with positive history of malignant disease and others (proteinura 11.7 g/du (25-75C 3.4-15.7) vs. 5.8 g/dU (25-75C 3.4 – 8.5); p=0.232 and eGFR 57 ml/min/1,73m2 (25C-75C 14 – 59) vs. 81 ml/min/1.73m2 (25-75C 54 – 100); p=0.066). During follow up 11 (9%) patients developed tumor, median age of pts 67 y (min – max 59 – 71); nine solid tumors most comonly of gastrointestinal origin (pancreas, colon N=5 (45%)), then pulmonum (N=2(18%)) and urogenithal origin (ca renis and prostate N=2 18%). Also two hematological malignancies (B-ALL, B-NHL) occurred. Median time till confirmed malignant disease was 9 y (min – max 5 -24). At the time of detecting the tumor six (54%) patients were in complete and partial remission (4 and 2) and 2 (18%) patients had nephrotic syndrome. No difference was observed in proteinuria between those with malignant condition and other MN patients (1,4 g/dU (25 – 75C 0.2 – 5.6) vs. 0,29 g/dU (25 – 75C 0.13 – 0.74); P=0.154). MN patients with malignant disease during follow up had lower estimated glomerular filtration rate (eGFR 45 ml/min/1,73m2 (25 – 75C 22 – 70) vs. 77 (25 – 75C 58 – 92); p=0.010). There was no difference in cummulative dose of cyclophosphamide between those who developed tumor with others (24 g(25 – 75C13.5 – 30) vs. 27 g(25 – 75C 15 – 38)p=0.592). Conclusion Our data emphasize the need for long term follow up of patients with membranous nephropathy despite accomplishing remission of MN and period screening for malignant disease, especially in those with deteriorating kidney function.

P649 Ulcerative Colitis Narrative Japanese survey: Identifying gaps between patient and healthcare professional perspectives on communication and disease management to optimise patient care

Abstract Background The Ulcerative Colitis (UC) Narrative is a global initiative examining perspectives on multiple aspects of UC via 2 related surveys (1 patient [pt]-based and 1 healthcare professional [HCP]-based), with the aim of improving understanding of the impact of UC and identifying gaps in optimal care. We present survey responses from pts and HCPs in Japan, a subanalysis of the global UC Narrative. Methods Surveys were conducted by The Harris Poll between Nov 2017 and Jan 2018. Pts (≥18 years of age) met the following criteria: had a diagnosis of UC (confirmed by endoscopy), had not had a colectomy, had taken prescription UC medication beyond 5-aminosalicylates, and had visited a gastroenterologist/internist in the previous year. HCPs were required to see ≥5 pts with UC per month, and ≥10% of their current pts had to be taking a biologic for their UC. Self-reported treatment history was used as a proxy for disease severity, and &amp;gt;80% of pt respondents were required to have moderate to severe UC. Results 210 pts and 151 HCPs in Japan responded. The mean age of pts with UC was 44.3 (standard deviation 11.6; median 44) years, and 73% were male. Most (85%) pts were satisfied with their communication with their HCP. HCPs slightly underestimated pt satisfaction, believing that, on average, 71% of their pts were satisfied. However, most pts (65%) and HCPs (82%) wished for more discussion about goals for managing or treating UC. Most (83%) pts said they were honest with their HCP when discussing their experiences with UC, although almost half (45%) said they regretted not telling their HCP more; most (75%) HCPs felt that their pts were being honest with them. Over half (55%) of pts said they were hesitant to tell their HCP if they did not take their medication exactly as prescribed; however, most (79%) HCPs believed that &amp;gt;50% of their pts adhered to treatment. HCPs underestimated the importance of toileting accidents to pts (28% vs 54%), and overestimated the importance of mucosal healing (59% vs 29%) (Figure 1). Some pts had misconceptions about treatment: only 69% knew that it was not OK to stop taking UC medications once they felt better, only 76% knew that it was not OK to keep using steroids as a long-term maintenance medication, and only 60% knew that it was possible for their body to stop responding to biologics (Figure 2). Most (71%) HCPs believed that pt advocacy organisations are important, but only recommended them to 26% of pts; only 38% of pts had interacted with one. Conclusion There was a high level of concordance in responses between pts in Japan and their HCPs; however, this survey revealed several gaps between pt and HCP perspectives. Consequently, the importance of pt-HCP communication in treat-to-target strategies remains.

Genotype-phenotype association in patients with arrhythmic variant of non-compaction cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Purpose. To evaluate the genotype-phenotype association in Belarusian patients with non-compaction cardiomyopathy (NCCM) and clinically significant ventricular arrhythmias. Methods. The study included 170 unrelated pts with NCCM prospectively observed in the RSPC "Cardiology", who underwent 24-hour Holter ECG monitoring for 12 months after entering the study. The median follow-up was 36 months [6; 152,0]. The median age of pts was 42 [18; 69] years, men – 63,2%. The arrhythmic phenotype of NCСM was diagnosed by the presence of unexplained syncope; nonsustained ventricular tachycardia, defined as ≥3 consecutive ventricular contractions lasting &amp;lt;30 seconds with a frequency of ≥120 bpm; the presence of ≥ 500 ventricular premature beats (VPB) per day. The diagnosis of NCCM was established on the basis of the following criteria: 1) Echocardiography of the R. Jenni criteria; 2) CMR of the S. Petersen and A. Jaquier criteria. The mutations search in the coding sequences of 174 genes was performed in 30 unrelated pts with NCCM using next generation sequencing (NGS). Results. In 76 out of 170 (44,7%) pts, clinically significant arrhythmias were the leading manifestation of the disease. Nonsustained VT was recorded in 54 (71,1%) pts, sustained VT – in 15 (19,7%) pts, VPB more than 500 per day – in 50 (65,8%), chronic AF with episodes of nonsustained VT was noted in 34 (44,7%) pts. During the follow-up period (median follow-up of 36 months), devices (ICD/CRT-D) were implanted in 15 (19,7%) pts, appropriate shocks were observed in two of them; three pts died, among which SCD occurred in one patient with CRT-D therapy, which was ineffective in stopping sustained VT. NGS sequencing revealed 40 changes in the nucleotide sequence (5 pathogenic mutations, 30 variants with uncertain significance (VUS), 5 new substitutions) in 27 genes in 26 (86,7%) probands. The proportion of mutations in sarcomeric proteins genes was 26,9%, and in ion channel proteins genes was 23,1%. Nucleotide changes in genes encoding structural proteins accounted for 11,5%. In 38,5% of cases, not one, but two or more rare mutations were detected, and in 30,8% – amino acid replacements were found in proteins of different functional classes. Conclusions. The frequency of multiple mutations was higher (38,5%) in the group of pts with the arrhythmic NCCM phenotype. In the group of pts with implantable devices (ICD/CRT-D), mutations in the genes of sarcomeric proteins were observed more often. The genetic characteristics of pts, along with their clinical characteristics, are markers of a high risk of developing life-threatening arrhythmias and can be additionally used for predicting adverse events in pts with NCCM, as well as for early diagnosis of the disease in their relatives.

Opioid screening and urine toxicology results in outpatient oncology palliative medicine.

e24068 Background: Opioid misuse is a major public health issue. Given widespread opioid prescribing in cancer patients (pts), screening for potential misuse is critical. There is lack of real-world data on opioid screening and urine toxicology testing in outpatient oncology palliative medicine. Methods: This is a retrospective clinical analysis of adult cancer pts previously consented for a pharmacogenomics specimen collection study between August 2019-March 2020. Pts completing ≥ 1 outpatient palliative medicine visit with at least half undergoing urine toxicology screening (UTS) per standard practice were included. Pt demographics, medication(s), UTS results, symptoms using Edmonton Symptom Assessment Scale, and opioid screening using Screener and Opioid Assessment for Patients with Pain - Short Form (SOAPP-SF) were collected at baseline and follow up visits, if available. The primary endpoint was the frequency and type(s) of non-compliant (NC) UTS. Secondarily, risk factors for NC UTS were evaluated using univariate and multivariate logistic regression. Results: Of 189 pts (632 visits), 113 underwent UTS, 125 SOAPP-SF, and 75 had both. The median age was 56, 56% were female, 58% white, 40% black, 48% had stage IV disease, and median pain score was 7. More black pts (72%) underwent UTS compared to white pts (53%) (p = 0.001). The mean age of pts with a UTS was 53 compared to 59 in those without UTS (p = 0.002). Oxycodone was the most prescribed drug (N = 125). Median SOAPP-SF was 3 (range 0-11); 38% had a score ≥ 4 (considered high risk). About half (54%; N = 61) who underwent a UTS were NC. Of these, 32 had 1 NC UTS, whereas 29 had 2 or more. The most common reason was presence of a substance not prescribed (N = 44 pts and 128 results), whereas 33 pts (53 results) were NC for substance(s) not present but prescribed. Four had presence of marijuana only and 21 with marijuana plus another NC substance; presence of cocaine and alcohol were the 2nd and 3rd most frequent aberrant result. Of those with a NC UTS and SOAPP-SF score (N = 44), 59% had a score ≥ 4. In univariate analyses, SOAPP-SF ≥ 4 (p = 0.004), nausea (p = 0.05), depression (p = 0.02), anxiety (p = 0.01), and prescriptions for antidepressants (p = 0.006), acetaminophen (p = 0.03), and/or dronabinol (p = 0.04), were associated with NC UTS. In multivariate analyses, SOAPP-SF Q4 (use of illegal drugs) (OR 2.86, 95% CI 1.64 to 5.02; p &lt; 0.001) and prescription with muscle relaxants (OR 2.90, 95% CI 1.19 to 7.09; p = 0.019) were associated with increased odds of a NC UTS. Conclusions: About half of those undergoing UTS were NC. SOAPP-SF Q4 and prescription with muscle relaxants were associated with a NC UTS. Overall, pt demographics (e.g. younger, more female, more black patients, severe pain) varied from the typical cancer population. Screening using SOAPP-SF, UTS, pain contracts, prescription drug monitoring databases, and evaluating pt-specific risk factors is important to reduce opioid misuse risk.