bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of clinical trial enrollment and impact on outcome in children and adolescents with acute lymphoblastic leukemia: A population based study.
Authors: Gibson Paul James , Athale Uma H. , Breakey Vicky Rowena , Mittmann Nicole , Bassal Mylene , Silva Mariana , Patel Serina , Zabih Veda , Pechlivanoglou Petros , Pole Jason D. , Gupta Sumit 
Published: June 2021

7031 Background: Outcomes in pediatric acute lymphoblastic leukemia (ALL) have shown remarkable improvements in large part due to sequential clinical trials. Concerns however persist around whether access to clinical trials is equitable. It is also unclear whether patient outcomes are improved simply by enrolling on a clinical trial. Our objective was to therefore determine which patient and disease-related factors are associated with enrollment, and whether enrollment was associated with clinical outcomes among children and adolescents with ALL in a single-payer health system in Ontario, Canada. Methods: We included all Ontario patients diagnosed with ALL between 0-18 years of age from 2002-2012 treated at a pediatric center, identified through a provincial pediatric cancer registry. Clinical trial availability was determined by whether each patient’s primary institution had an open frontline trial for which the patient was eligible at the time of their diagnosis, considering individual disease characteristics such as lineage, central nervous system (CNS) status and risk group. Demographic, disease, trial enrolment, and outcome data were obtained through chart abstraction. Logistic regression models determined factors associated with trial enrolment, while Cox proportional hazard models determined factors associated with event-free and overall survival (EFS, OS). Results: Of 858 patients, 693 (81%) were eligible for an open clinical trial at their time of diagnosis. 476 (69%) enrolled on a trial. In adjusted analyses, age > 15 years (odds ratio 0.4 vs. age 5-9, 95th confidence interval (95CI) 0.2-0.8; p = 0.01) and CNS3 disease (OR 0.38 vs. CNS1, 95CI 0.17-0.83; p = 0.01) were significantly associated with decreased likelihood of enrolment, while sex and neighborhood income quintile were not associated with enrolment. Adjusted for disease and demographic factors, clinical trial enrolment was not significantly associated with either EFS (hazard ratio (HR) 1.1, 95CI 0.7-1.7; p = 0.83) or OS (HR 1.3, 95CI 0.7-2.5; p = 0.44). Conclusions: The majority of patients with ALL eligible for available clinical trials at their time of diagnosis were enrolled. While no disparities in enrolment by income status were noted, adolescents were substantially less likely to participate in trials even within pediatric centers. Studies of mechanisms underlying this disparity are warranted in order to design and implement effective interventions targeting increased enrolment rates in this patient population. Our results however also suggest that clinical trial enrolment on its own is not associated with improved outcomes in the context of a single payer health system.
Outcomes with COVID-19 in hematopoietic stem cell transplant and cellular therapy patients.
Authors: Mushtaq Muhammad Umair , Luder Mary , Shahzad Moazzam , Ahmed Nausheen , Abdelhakim Haitham , Bansal Rajat , Balusu Ramesh , Chaudhary Sibgha Gull , DeJarnette Shaun , Divine Clint , Kribs Robert , Shune Leyla , Singh Anurag K , Abhyankar Sunil H. , Ganguly Siddhartha , McGuirk Joseph 
Published: June 2021

7033 Background: The Coronavirus Disease 2019 (COVID-19) has caused over 25 million infections in the US with over 0.4 million deaths. Hematogenic stem cell transplant (HCT) or cellular therapy (CT) recipients have a high risk of mortality with COVID-19 due to profound immune dysregulation. We aimed to assess the outcomes with COVID-19 in HCT/CT recipients. Methods: A single-center prospective study was conducted, including all (n=40) adult HCT/CT patients who were diagnosed with COVID-19 at the University of Kansas from Apr 2020 to Jan 2021. Baseline and disease-related characteristics were ascertained from medical records. Data were analyzed using SPSS version 21 (SPSS Inc, Chicago, IL). Bivariate analyses, using chi-square and t-test, and logistic regression analyses were conducted. Results: The study included 40 COVID-19 patients (72.5% Oct 2020-Jan 2021), including allogeneic HCT (n=25), autologous HCT (n=13) and CAR-T CT (n=2) with median time since HCT/CT of 12.4 (1-201.9), 37.2 (0.4-118.7), and 3.8 (2.8-4.8) months. Seventy percent were Caucasians and 17.5 were Hispanics. Primary hematologic malignancy was myeloid (37.5%), lymphoid (35%) or plasma cell disorder (27.5%). Myeloablative conditioning was performed in 65% of patients. Donors were autologous (37.5%), matched sibling (17.5%), matched unrelated (22.5%) and haploidentical (22.5%). COVID-19 was mild (42.5%), moderate (42.5%) or severe (15%). Clinical findings included pneumonia (62.5%), hypoxia (25%) and ICU admission (17.5%) while therapies included remdesivir (47.5%), convalescent plasma (40%), dexamethasone (25%) and monoclonal antibodies (17.5%). Concurrent cancer treatment, other infections and active GVHD were reported in 25% (all myeloma), 20% and 32.5% of patients. After a median follow-up of 74 days (7-269), the mortality rate was 12.5% in all patients and 20% in allo-HCT patients. Significant predictors of COVID-19 severity included allogeneic HCT, concurrent immune suppression and elevated inflammatory markers. (Table). Conclusions: Hematopoietic stem cell transplant recipients have an increased risk of mortality with COVID-19. Our findings confirm the need for vaccination prioritization, close monitoring, and aggressive treatment in HCT/CT patients.[Table: see text]
The effect of body mass index on efficacy and safety of bosutinib or imatinib in patients with newly diagnosed chronic myeloid leukemia.
Authors: Brümmendorf Tim H. , Cortes Jorge E. , Busque Lambert , Gambacorti-Passerini Carlo , Stenke Leif , Viqueira Andrea , Leip Eric , Purcell Simon , Deininger Michael W 
Published: June 2021

7037 Background: Bosutinib (BOS) is approved for the treatment (Tx) of Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) resistant/intolerant to prior therapy and newly diagnosed Ph+ chronic phase (CP) CML. Body mass index (BMI) was shown to influence Tx response with front-line dasatinib vs imatinib (IMA). We report the efficacy and safety of BOS and IMA by BMI in patients (pts) with newly diagnosed CP CML. Methods: In the open-label BFORE trial, pts were randomized to receive 400 mg once daily BOS or IMA. Outcomes were assessed according to baseline BMI ≥25 or = 25 kg/m2. This post hoc analysis was based on the final 5-y analysis (database lock: June 12, 2020). Results: In the BOS and IMA arms, respectively, 149 (56.4%) vs 115 (43.6%) pts and 145 (54.3%) vs 122 (45.7%) pts had BMI ≥25 vs = 25. In both the BOS and IMA arms, median Tx duration and time on study was 55 mo for pts with BMI ≥25 or = 25; respective median dose intensity was 394 vs 393 mg/d and 400 vs 400 mg/d. Molecular response (MR) rates are shown in the table. Cumulative incidence of major MR was similar in pts with ≥25 vs = 25 receiving BOS (HR 0.99; 95% CI 0.74−1.31) or IMA (HR 1.09; 95% CI 0.81−1.47). Event-free survival (EFS) and overall survival (OS) rates at 60 mo are shown in the table. Most common reasons for Tx discontinuation were adverse events (AEs) (BOS 28.2 vs 20.0%; IMA 13.3 vs 10.7%) and lack of efficacy (BOS 5.4 vs 5.2%; IMA 16.1 vs 19.8%). In pts with BMI ≥25 vs = 25, dose reductions and interruptions due to Tx-emergent AEs (TEAEs) occurred in 43.6 % vs 46.2% and 66.4% vs 69.7% of pts with BOS and 24.5% vs 24.6% and 40.6% vs 50.8% with IMA. Any grade TEAEs in ≥30% of pts with BMI ≥25 vs = 25 were diarrhea (73.8 vs 73.1%), nausea (40.9 vs 31.9%), thrombocytopenia (30.9 vs 41.2%), increased alanine (37.6 vs 28.6%) and aspartate aminotransferase (30.2 vs 20.2%) with BOS and diarrhea (49.0 vs 29.5%), nausea (46.2 vs 37.7%), muscle spasms (33.6 vs 26.2%), neutropenia (14.7 vs 32.0%) and thrombocytopenia (10.5% vs 30.3%) with IMA. Conclusions: Efficacy of BOS was consistent in pts with BMI ≥25 or = 25; however, with IMA a low (vs high) BMI appeared to be associated with worse survival outcomes. Differences in certain TEAEs were observed between BMI subgroups in both treatment arms. Clinical trial information: NCT02130557. [Table: see text]
Clinical characteristics, treatment patterns, and overall survival of real-world patients with idiopathic multicentric Castleman disease.
Authors: Cohen Aaron B. , Swaminathan Akshay , Wang Xiaoliang , Zamora Stephen , Repucci Michael A , Kelly Jonathan , Hannan Mark D , Sepler Daniel , Sridharma Suganya , Orlando Abigail , Leybovich Barry , Fajgenbaum David 
Published: June 2021

7048 Background: Castleman disease (CD) has three subtypes: Unicentric (UCD), Human herpesvirus-8 associated multicentric (HHV-8 MCD) and idiopathic multicentric (iMCD). Outcomes for patients with iMCD are poor and treatment options are limited, with only one FDA-approved therapy (siltuximab in April 2014). Further, the lack of CD-specific ICD codes until 2017 has limited real-world evaluation. We identified iMCD patients in an electronic health record (EHR)-derived dataset and described their clinical characteristics, treatment patterns, and real-world overall survival (rwOS). Methods: Patients with a possible diagnosis of CD as of 8/31/20 were identified from the nationwide deidentified Flatiron Health EHR-derived database using patient-level structured data (e.g., ICD-9/10 codes) and unstructured data (e.g., clinician notes), curated via technology-enabled manual abstraction to confirm CD diagnosis and treatments received. Descriptive statistics summarized patient characteristics and treatment patterns. Patients without structured data within 90 days after diagnosis were excluded from treatment patterns analyses. 5-year rwOS rate was estimated from diagnosis date using the Kaplan-Meier estimator. Results: 747 patients with possible CD were identified, of whom 453 were confirmed to have CD by abstraction (172 UCD, 100 iMCD, 36 HHV-8 MCD, and 145 unclassified). IMCD patients were predominantly female (53%), white (58%), and treated at community sites (70%). Of the 52 iMCD patients with evidence of structured data within 90 days after diagnosis and who had at least one documented line of therapy, the most common first-line therapies were siltuximab-based therapy (42.3%), rituximab monotherapy (36.5%), and chemotherapy-based treatment (13.5%). Among 28 iMCD patients with evidence of second-line therapy, the most common treatment was rituximab monotherapy (35.7%). Among 60 iMCD patients diagnosed on or after siltuximab approval in April 2014 (including those without evidence of any treatment), 26 (43%) received siltuximab at some point. 5-year rwOS rate for the 100 iMCD patients was 75% [95% CI: 63-89%]. Conclusions: This is the first study to utilize a large EHR-derived database to describe characteristics, treatment patterns, and overall survival of iMCD patients in real-world practice. Less than half of iMCD patients diagnosed on or after the date of FDA approval for siltuximab received it at some point. Future work should focus on characterizing the drivers of poor patient outcomes.
Polatuzumab vedotin + obinutuzumab + venetoclax in patients with relapsed/refractory (R/R) follicular lymphoma (FL): Primary analysis of a phase 1b/2 trial.
Authors: Bannerji Rajat , Yuen Sam , Phillips Tycel Jovelle , Arthur Christopher , Isufi Iris , Marlton Paula , Seymour John Francis , Corradini Paolo , Molinari Annalia , Gritti Giuseppe , Emmons Robert , Hirata Jamie , Musick Lisa , Saha Sourish , Croft Brandon , Flowers Christopher 
Published: June 2021

7534 Background: Polatuzumab vedotin (Pola) + obinutuzumab (G) demonstrated activity and tolerability in a Phase 1b/2 trial of patients (pts) with R/R FL (Phillips, et al. Blood 2016). Preclinical studies with venetoclax (Ven) showed that concurrent treatment with Pola promotes MCL-1 degradation, a known mechanism of resistance to Ven, and enhances in vivo anti-tumor efficacy (Amin, et al. AACR 2020). Here, we report the primary safety/efficacy analysis with Pola-G-Ven in a Phase 1b/2 study of pts with R/R FL (GO29833; NCT02611323). Methods: Pts received induction treatment every 21 days (D) x six cycles (C) of: Pola 1.4–1.8mg/kg intravenously (IV) in dose escalation (DE) or recommended Phase 2 dose (RP2D) on D1; G 1000mg IV (C1: D1, D8, D15; C2–6: D1); and oral Ven 200–800mg (DE or RP2D; D1–21). Pts with complete response/partial response/stable disease (CR/PR/SD) at end of induction (EOI) received maintenance with G (1000mg on D1 every 2 months [mo] for 24 mo) and Ven (200–800mg daily) for 8 mo. Primary endpoints were safety/tolerability and positron emission tomography (PET)-CR rate at EOI by independent review committee (IRC) using modified Lugano criteria. Results: At the primary analysis (Oct 05, 2020), 74 pts were enrolled. Median pt age was 64 years (range 36–78); male (57%); Ann Arbor Stage III–IV (86%); FL International Prognostic Index high risk ≥3 (55%); bulky disease ≥7cm (16%); prior lines of therapy ≥2 (74%); refractory to: last prior therapy (51%), any prior anti-CD20 therapy (55%), both anti-CD20 therapy and an alkylating agent (double refractory; 55%). Grade 3–4 adverse events (AEs) were experienced by 73% of pts; most commonly, neutropenia (39%), thrombocytopenia (19%), and infections (16%; mainly pneumonia). AEs led to dose reduction in 38% and interruption in 68% of pts (mainly modifications to Ven). One fatal AE was reported (pneumonia). In total, 49 pts were treated at RP2D (Pola 1.8mg/kg + Ven 800mg) and were evaluable for efficacy. PET-CR rate at EOI by IRC was 57% (Table). With a median follow-up of 14.4 mo (range 8.2–28.4), the 12-mo progression-free survival (PFS) was 73% (95% confidence interval: 59.4–86.9). Median PFS was not reached. Conclusions: The safety profile of Pola-G-Ven is consistent with the known profiles of the individual drugs. Response rates at EOI with Pola-G-Ven are encouraging in this R/R FL patient population. Additional follow-up is needed to assess PFS benefit during maintenance treatment and beyond. Clinical trial information: NCT02611323. [Table: see text]
Assessing financial difficulty in patients with multiple myeloma: Preliminary results of ALLIANCE A231602CD.
Authors: Conti Rena M. , McCue Shaylene , Dockter Travis , Rapkin Bruce D. , Dusetzina Stacie , Bennett Antonia Vickery , Gracia Gabriela , Johnson Michelle E. , Martin Sarah A. , Chang George J. , Richardson Paul G. , Behrens Robert J. , Weiss Elisa S. 
Published: June 2021

8031 Background: New orally administered anticancer treatments have launched in recent years, promising gains in survival and quality of life, but with high prices.Financial difficulties encountered over the course of cancer diagnosis and treatment is a growing concern. These difficulties include inability to pay for basic necessities, presence of medical debt, and high out of pocket burdens relative to income. The primary objective of this study was to estimate the proportion of patients with multiple myeloma (MM) who experience financial difficulties in the past 12 months.Methods: Data collection entailed a comprehensive, theoretically grounded telephone survey and companion medical chart abstraction. Subjects included individuals with a current diagnosis of MM whose current or recent treatment included pharmaceutical-based care and who were not enrolled in a treatment-based trial. Practices eligible to recruit respondents included 44 NCORP affiliates of the Alliance. 14 geographically diverse NCORP affiliates participated between 11/2019 and 6/2020. The primary endpoint of the study was the proportion of subjects who reported financial difficulty in the past 12 months, as measured by the EORTC QLQ-C30 item #28. This proportion and 95% Wilson score confidence interval were estimated for all MM patients who responded to the financial difficulty question ((# reported financial difficulty)/(total # in that category who answered the question)). NCI Central IRB approved this study. Results: 393 subjects were recruited. 304 subjects completed the survey (77.4% response rate). Mean age was 67.5 years (SD 9.8), 143 (46.4%) were female, 24 (7.8%) self-reported race as ‘Black or African American’, 82 (26.6%) reported insured by government insurance Medicare only, 116 (38.2%) reported highest education as high school or below, and 94 (30.5%) reported high income. Mean time from diagnosis to survey enrollment was 3.6 years (SD 4.5). 292 (95.1%) were currently receiving treatment and 192 (62.5%) reported currently receiving a pre-defined ‘expensive’ oral pharmaceutical-based cancer treatment. 20.2% (95% CI:16.1%, 25.0%) reported financial difficulties. Conclusions: This is the first national study to systematically assess the prevalence of financial difficulties and its correlates among MM patients. Approximately 1 in 5 surveyed patients reported financial difficulties. Results of this study aim to inform efforts to improve financial navigation and resources for cancer patients.
Relationship between corneal exam findings, best-corrected visual acuity (BCVA), and ocular symptoms in patients with relapsed or refractory multiple myeloma (RRMM) receiving belantamab mafodotin (belamaf).
Authors: Terpos Evangelos , Badros Ashraf , Popat Rakesh , Rodríguez-Otero Paula , Farooq Asim , Jeng Bennie , Degli Esposti Simona , Lewis Eric , Gupta Ira , Opalinska Joanna , Palumbo Antonio , Trudel Suzanne 
Published: June 2021

8033 Background: Belantamab mafodotin (GSK2857916; belamaf; BLENREP) is a B-cell maturation antigen (BCMA)-targeting antibody–drug conjugate approved in the US and EU as a monotherapy for the treatment of adult patients with RRMM. Ocular events (OEs) during the pivotal DREAMM-2 trial (NCT03525678) included corneal exam findings (punctate keratopathy and microcyst-like epithelial changes), BCVA changes, and ocular symptoms. Dose reductions or delays based on corneal exam findings and BCVA were used to manage OEs. Here we performed a post hoc investigation of relationships between corneal exam findings, BCVA changes, and patient-reported ocular symptoms to explore if BCVA changes and symptoms could guide dosing, rather than corneal exams. Methods: Eye evaluations (including a corneal exam and BCVA assessment of Snellen visual acuity) were performed on all patients receiving single-agent belamaf (2.5 mg/kg) by ophthalmologists at baseline and prior to each belamaf dose. Changes in the corneal epithelium (Ker) and BCVA were both assessed as per protocol-defined criteria and assessment of grade (Gr) was based on the worse eye. BCVA grading was relative to baseline. Patient-reported ocular symptoms were reported as per the Common Terminology Criteria for Adverse Events. Results: In 12.5% of eye evaluations Gr 3–4 Ker was associated with minimal or no (Gr ≤1) BCVA changes. When patient-reported ocular symptoms were also considered, only 7.5% of evaluations found Gr 3–4 Ker with Gr ≤1 BCVA changes or ocular symptoms. Mild or no (Gr ≤2) Ker was associated with Gr ≤1 BCVA changes in 59.5% of evaluations, or in 38.8% of evaluations with no ocular symptoms reported. Overall, Gr 3–4 Ker were found in 24.9% of evaluations; by contrast, patients had Gr 2–4 BCVA changes or ocular symptoms in 53.7% of evaluations. Association of corneal epithelium changes (Ker) with BCVA changes and ocular symptoms. Conclusions: These findings highlight that BCVA changes and ocular symptoms should be further investigated to determine if they can be used as alternatives (eg, frequency of eye examinations based on symptoms) for the management of belamaf dosing to potentially reduce the burden on patients and healthcare professionals. Clinical trial information: NCT03525678. [Table: see text]
Characteristics of neurotoxicity associated with idecabtagene vicleucel (ide-cel, bb2121) in patients with relapsed and refractory multiple myeloma (RRMM) in the pivotal phase II KarMMa study.
Authors: Manier Salomon , Kansagra Ankit J. , Anderson, Jr Larry D. , Berdeja Jesus G. , Jagannath Sundar , Lin Yi , Lonial Sagar , Shah Nina , Raje Noopur S. , Siegel David Samuel DiCapua , Oriol Albert , Truppel-Hartmann Anna , Rowe Everton , Patel Payal , Agarwal Amit , Campbell Timothy B. , Rodríguez-Otero Paula , Munshi Nikhil C. ,   on behalf of the KarMMa Study Investigators
Published: June 2021

8036 Background: Ide-cel, a BCMA-directed CAR T cell therapy, showed promising efficacy in patients (pts) with RRMM in the KarMMa study with an ORR of 73% and a CRR of 33% across target doses of 150–450 × 106 CAR+ T cells (Munshi NC, et al. J Clin Oncol 2020;38[suppl 15]. Abstract 8503). Associations of neurotoxicity (NT) with pt and disease characteristics, pt management, and impact on outcomes in the KarMMa study are reported here. Methods: Enrolled pts were triple-class exposed and refractory to their last regimen, with ide-cel given at target doses of 150, 300, or 450 × 106 CAR+ T cells after lymphodepletion (NCT03361748). Investigator-identified NT events were captured under the single preferred term of neurotoxicity and graded according to NCI CTCAE v4.03. Events were managed with corticosteroids (CS), anakinra (ANR), and tocilizumab (Toci) as needed. Results: Of 128 pts treated with ide-cel, NT was reported in 23 (18%); 12 pts (9%) had maximum grade (gr) 1 NT, 7 (5%) had gr 2, and 4 (3%) had gr 3. No gr 4 or 5 NT occurred. Most baseline characteristics were similar in pts with and without NT, including stage III disease (22% and 15%), high-risk cytogenetics (39% and 34%), and extramedullary disease (35% and 40%); exceptions were high tumor burden (65% and 48%) and sex (48% and 62% men). NT (any gr/gr 3) occurred in 0%/0%, 17%/1%, and 20%/6% of pts at doses of 150, 300, and 450 × 106 CAR+ T cells. Median time to onset was similar regardless of gr, and there were no late-onset events (Table). NT was managed with CS in 10 pts (43%), Toci in 3 (13%), and ANR in 1 (4%). Median (range) time to first use of CS was 2 d (1–6). ORR and DOR were similar in pts with and without NT (Table). All NT occurred in the proximity of cytokine release syndrome (CRS) events with the start date of NT events either overlapping with or occurring within 1 wk of the start of a CRS event. Conclusions: NT occurred early in the KarMMa study, was generally of short duration, and was mostly gr 1/2 with no gr ≥4 events. All NT was proximal to CRS. Pts with NT had a favorable ORR after ide-cel treatment. These results continue to demonstrate the durable efficacy and tolerability of ide-cel in pts with RRMM. Clinical trial information: NCT03361748. [Table: see text]