bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maxed out: Reaching the annual maximum out-of-pocket limit among insured patients diagnosed with cancer.
Authors: Banegas Matthew P. , Dickerson John F. , Petrik Amanda F , Anderson Melissa L. , Keast Erin , Ramaprasan Arvind , Wallace Jamie , Henrikson Nora B. 
Published: June 2023

6646 Background: Patients with cancer face potentially high out-of-pocket costs associated with their medical care, which may lead to adverse medical and financial outcomes. Depending on their health insurance plan, patients may have to pay several thousands for medical care costs until they reach the annual maximum out-of-pocket [MOOP] spending limit; after which care costs are covered by insurance. The purpose of this study was to measure the proportion of adult patients who reach their health plan MOOP limit in the year of cancer diagnosis. Methods: Electronic health record data from 13,057 patients aged ≥18 years, diagnosed with cancer between Jan. 1, 2016–March 31, 2021 [index cancer], with ≥12 months of continuous health insurance coverage pre-cancer diagnosis were included. The primary outcome was defined as reaching the MOOP limit in the health plan benefit year of index cancer diagnosis (binary, yes/no). We additionally created a secondary outcome using 3 categories: (i) did not reach MOOP; (ii) reached MOOP prior to cancer diagnosis; (iii) reached MOOP after cancer diagnosis. Descriptive statistics were used to assess the distribution of outcomes across patient characteristics including health insurance type (e.g., commercial), high-deductible health plan (HDHP), cancer type, age at diagnosis, and Census-level household income was included. Multivariable logistic regression estimated the association between patient characteristics and the primary outcome. Complete case analyses were performed using Stata 16.1. Results: Patients’ mean age was 66 years (standard deviation [sd]: 13) and mean Census-level household income was $73,100 (sd: $24,000). Approximately 40% of patients had commercial health insurance and 62% had Medicare; 2% (n=283) had a HDHP. Breast (18%), lung (11%) and prostate (11%) cancers were most common. The mean annual MOOP limit was $3,040 for commercial plans and $2,688 for Medicare plans. Among patients with a commercial plan insurance, 46% reached their MOOP limit including 8% before and 37% after cancer diagnosis. For Medicare patients, 20% reached their MOOP limit, including 3% before and 17% after cancer diagnosis. Patients with a HDHP (adjusted Odds Ratio [aOR]: 2.61, 95% CI: 1.96-3.47), breast cancer (aOR: 2.29, 95% CI: 1.84-2.84), and lung cancer (aOR: 2.71, 95% CI: 2.04-3.61) had significantly greater odds of reaching the MOOP than those with a non-HDHP and other cancers. Household income was also significantly associated (aOR: 0.97, 95% CI:0.95-0.99) with reaching the MOOP. Conclusions: A substantial proportion of patients reach the annual MOOP limit during the year of cancer diagnosis, representing a population at high-risk for medical financial hardship. Future longitudinal studies are needed to assess the trajectory of OOP spending and implications on care utilization and health outcomes.
IMerge: Results from a phase 3, randomized, double-blind, placebo-controlled study of imetelstat in patients (pts) with heavily transfusion dependent (TD) non-del(5q) lower-risk myelodysplastic syndromes (LR-MDS) relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESA).
Authors: Zeidan Amer Methqal , Platzbecker Uwe , Santini Valeria , Fenaux Pierre , Sekeres Mikkael A. , Savona Michael R. , Madanat Yazan F. , Diez-Campelo Maria , Valcarcel David , Illmer Thomas , Jonasova Anna , Belohlavkova Petra , Sherman Laurie Jill , Berry Tymara , Dougherty Souria , Shah Sheetal , Sun Libo , Wan Ying , Huang Fei , Komrokji Rami S. 
Published: June 2023

7004 Background: Unmet needs remain for red blood cell (RBC) TD pts with LR-MDS R/R or ineligible for ESA. In P2 of the IMerge study (NCT02598661), heavily RBC TD ESA R/R non-del(5q) LR-MDS pts naive to lenalidomide and hypomethylating agents (len/HMA) treated with imetelstat, a telomerase inhibitor, achieved durable and continuous transfusion independence (TI). We report primary data from the P3 study of imetelstat in such pts. Methods: Heavily RBC TD ESA R/R non-del(5q) LR-MDS pts naive to len/HMAs were randomized 2:1 to receive imetelstat 7.5 mg/kg or placebo every 4 wks. Primary endpoint was 8-wk TI; subgroup analyses included IPSS risk, prior transfusion burden and ring sideroblast (RS) status. Secondary endpoints included 24-wk TI, TI duration and hematologic improvement-erythroid (HI-E). Variant allele frequency (VAF) changes were explored. Results: As of Oct 2022, 178 pts were randomized. The primary endpoint was met (Table); 39.8% vs 15.0% of pts receiving imetelstat vs placebo, respectively, achieved 8-wk TI. The rate of 8-wk TI was significantly higher with imetelstat vs placebo across subgroups, including RS negative pts. Median TI duration was significantly longer for imetelstat vs placebo, 51.6 vs 13.3 wks, P < 0.001. Pts receiving imetelstat had significantly higher mean hemoglobin (P < 0.001) and fewer transfusions (P = 0.042) over time than those on placebo. In 3 of 4 genes frequently mutated in MDS, VAF reduction was significantly greater in pts treated with imetelstat than placebo: SF3B1 (P < 0.001), TET2 (P = 0.032), DNMT3A (P = 0.019) and ASXL1 (P = NS). SF3B1 VAF reduction correlated with longer TI duration, P < 0.001. No new safety signals were identified. The most common Grade 3/4 AEs were thrombocytopenia and neutropenia, with similar rates of Grade ≥3 bleeding and infections on imetelstat and placebo. In pts treated with imetelstat, cytopenias were manageable, of short duration, and >80% were reversible to Grade ≤2 within 4 wks. Conclusions: For this LR-MDS pt population, imetelstat demonstrated statistically significant and clinically meaningful efficacy with high 8- and 24-wk TI rates, prolonged TI duration and increased hemoglobin. VAF reduction and its correlation to clinical endpoints support imetelstat’s disease-modifying potential. Safety results were consistent with prior reported experience. Clinical trial information: NCT02598661 . [Table: see text]
Updated efficacy and safety data from the AGILE study in patients with newly diagnosed acute myeloid leukemia treated with ivosidenib + azacitidine compared to placebo + azacitidine.
Authors: De Botton Stéphane , Montesinos Pau , Vives Polo Susana , Zarzycka Ewa , Wang Jianxiang , Riva Marta , Heuser Michael , Calado Rodrigo T. , Schuh Andre C. , Yeh Su-Peng , Hui Jianan , Gianolio Diego A. , Patel Prapti Arvind , Recher Christian , Dohner Hartmut 
Published: June 2023

7012 Background: Ivosidenib (IVO) is a potent oral targeted inhibitor of mutant IDH1. In the AGILE study in patients (pts) with newly diagnosed IDH1-mutated acute myeloid leukemia, IVO plus azacitidine (AZA) significantly improved event-free survival (EFS), overall survival (OS), complete remission (CR), and CR or CR with partial hematologic recovery (CR+CRh) rates v placebo (PBO) plus AZA. As of March 2021, median OS (mOS) was 24 months (IVO+AZA) v 7.9 months (PBO+AZA; HR: 0.44; p=0.0005). Long-term follow-up data are presented. Methods: In the double-blind AGILE study, pts were randomized 1:1 to IVO 500 mg QD + AZA 75 mg/m2 SC or IV for 7 days in 28-day cycles, or PBO+AZA. Long-term follow-up data (June 2022) for OS, blood count recovery, transfusion independence and safety are described here. Results: 148 pts were randomized: 73 to IVO+AZA; 75 to PBO+AZA. Median treatment duration was 10.8 months (IVO+AZA) v 3.2 months (PBO+AZA). Five PBO+AZA pts crossed over to IVO+AZA after March 2021 (Table), and no adjustment was made for crossover in the updated OS analysis. At a median follow-up of 28.6 months, mOS was 29.3 months (95% CI 13.2, not reached) for IVO+AZA v 7.9 months (95% CI 4.1, 11.3) for PBO+AZA (HR 0.42 [0.27, 0.65]; p<0.0001). OS rates were 62.9% and 38.3% at 12 months and 53.1% and 17.4% at 24 months, with IVO+AZA and PBO+AZA, respectively. In the IVO+AZA arm, hemoglobin levels steadily increased from baseline (BL; 88.8 g/L) to cycle 8, and then stabilized; mean platelet count recovered from BL values (72.7 x 109/L) as early as week 8 (171.9 x 109/L) and remained stable; and mean neutrophil counts rapidly increased from BL (0.98 x 109/L) to week 3 (3.99 x 109/L) and week 4 (4.36 x 109/L), and then stabilized to within the normal range. Conversion from BL transfusion dependence (red blood cell and/or platelet transfusion dependence) to post-BL transfusion independence was significantly higher with IVO+AZA than PBO+AZA (53.8% v 17.1%, respectively; p=0.0004). There were fewer neutropenic fever events (27.8% v 33.8%) and infections (34.7% v 51.4%) with IVO+AZA than with PBO+AZA. TEAEs led to discontinuation of IVO+AZA or PBO+AZA in 26.4% and 25.7% of pts, respectively. Conclusions: Updated data on OS (>5 months longer mOS and a greater risk reduction in deaths compared to the initial analysis), transfusion independence, blood count recovery and safety confirms the clinically and statistically robust benefit in favor of IVO+AZA at long-term follow up. Patient disposition. Clinical trial information: NCT03173248 . [Table: see text]
Outcomes of 3- versus 5-day administration schedule of consolidation cytarabine in adults with acute myeloid leukemia (AML).
Authors: Diebold Kendall , Bachiashvili Kimo , Jamy Omer Hassan , Vachhani Pankit , Godby Kelly Nicole , Bhatia Ravi , Diamond Barry , Oliver Josh D , Moulton Kaitlin R , Rangaraju Sravanti 
Published: June 2023

7014 Background: Consolidation therapy with intermediate to high-dose cytarabine is critical to prevent relapse in AML. Cytarabine is typically administered every 12 hours on days 1, 3, 5. Two large studies have examined a condensed 3-day administration schedule in patients <60 years and demonstrated a shorter time to absolute neutrophil count (ANC) recovery without compromising long term outcomes. However, use of this regimen in patients ≥60 years has not been evaluated. Here we report our experience with the condensed administration schedule compared with the standard schedule in patients over and under 60 years. Methods: All patients with AML in first complete remission (CR) following intensive induction chemotherapy receiving consolidation at our institution between 1/1/2020 to 12/31/2021 were included in the study. Patients received cytarabine every 12 hours on days 1, 3, 5 (AC135) from 1/1/2020 – 12/31/2020 and cytarabine every 12 hours on days 1, 2, 3 (AC123) from 1/1/2021 – 12/31/2021. All patients received peg-filgrastim support. Data was collected to determine time to ANC recovery >1,000/µL, hemoglobin (Hb) >8g/dL, and platelets >75,000/µL. Comparison of continuous variables between two groups was done using multiple t-tests. Results: Between 1/1/2020 - 12/31/2021, 91 patients received at least one cycle of consolidation with 212 individual encounters. 38 patients received all cycles with AC135, 45 received AC123, and 8 received at least one cycle each of AC123 and AC135. Median age of the AC123 cohort was 50.2 years (range 19-72 years) and 54.3 years for the AC135 cohort (range 22-72 years). For patients ≥60 years of age, 33% (71/213) of the encounters were in the AC123 cohort and the rest in AC135 cohort. Median dose of cytarabine was 5,100 mg/dose in AC123 and 4,600 mg /dose in AC135 (p=0.02). Median time to ANC recovery, hemoglobin, and platelets as well as hospital-related outcomes are described in the table. In patients ≥60 years, median time to ANC recovery was 16.5 vs. 18.6 days (p = 0.03) and platelet recovery was 17.4 vs. 19.7 (p = 0.0008) in AC123 vs AC135 respectively. No neurotoxicity events were noted. Complication rates were similar in both arms. Conclusions: Our study demonstrates that AC123, as compared to AC135, is safe and leads to earlier hematopoietic recovery in adults under and over 60 years. AC123 should be considered the preferred schedule of consolidation therapy administration. [Table: see text]
Pelabresib (CPI-0610) monotherapy in high-risk essential thrombocythemia refractory or intolerant to hydroxyurea: Preliminary results from MANIFEST study.
Authors: Passamonti Francesco , Patriarca Andrea , Knapper Steven , Rivera Candido , Scandura Joseph , Devos Timothy , Granacher Nikki , Mead Adam J. , Oh Stephen , Palmer Jeanne M. , Rampal Raajit , Teichmann Lino , Cui Jie , Klein Sandra , Colak Gozde , Harrison Claire 
Published: June 2023

7019 Background: High-risk essential thrombocythemia (HR ET) is characterized by thrombocytosis, thrombohemorrhagic events and systemic symptoms. Pts can experience intolerance, inadequate response or loss of response to first-line cytoreductive therapies (hydroxyurea [HU] or interferon alfa-2a). BET protein inhibition is a novel therapeutic strategy that downregulates inflammatory cytokines and may inhibit differentiation and proliferation of abnormal megakaryocytes involved in ET pathogenesis. Results from the Phase 2 MANIFEST study (NCT02158858) suggested potentially encouraging clinical efficacy in pts with myelofibrosis treated with Pelabresib (PELA), an oral, small-molecule, investigational BET inhibitor. Here we present preliminary results from MANIFEST Arm 4 investigating PELA monotherapy in HR ET refractory or intolerant to HU. Methods: Eligible pts had platelets > 600 x 109/L and ≥ 2 symptoms (average score ≥3/ TSS≥15). Pts received PELA monotherapy 225 mg QD. The primary endpoint was complete hematologic response (CHR; normalization of platelet count (≤400 x 109/L), WBC count (≤10 x 109/L) confirmed after one cycle [after 3 weeks]) and normal spleen size. Secondary endpoints included partial HR (PHR; platelets 400–600 x 109/L and WBC ≤10 x 109/L), symptom improvement (≥50% TSS reduction) and safety. Results: As of July 2022, 20 pts with HR ET were treated: median age 64 yrs (42–83), median Hgb 13 (10–16) g/dL, median platelet count 772 (418–1255) x 109/L and median TSS 32.7 (6.9–123). The majority of pts had a hematologic response (90% [18/20] unconfirmed CHR or PHR); confirmed CHR was observed in 40% (8/20) (Table). Median platelet and WBC count at Wk 12 was 446 x109/L and 8.2 x 109/L, respectively. TSS reduction was reported in 86% (12/14 pts); median TSS reduction at Wk 12 was –31%. Hgb levels remained stable through Wk 24. The most common nonhematologic AEs were nausea (60%; 10% Gr 3), diarrhea (35%; 5% Gr 3) and dysgeusia (35%; no Gr 3). Hemorrhagic or thromboembolic events were reported in 30% pts (15% Gr 3). No events of thrombocytopenia and no Gr 4 events or higher were reported. Conclusions: Preliminary results from Arm 4 of the MANIFEST study suggest potential clinical benefit with PELA monotherapy in pts with HR ET refractory or intolerant to HU as supported by hematologic responses and symptom improvement. Safety results are consistent with the known safety profile of PELA and as expected in the underlying study population. Clinical trial information: NCT02158858 . [Table: see text]
Implications for acute myeloid leukemia (AML) treatment and care during the COVID-19 pandemic: A Connect Myeloid Registry study.
Authors: Scott Bart L. , Sekeres Mikkael A. , Garcia-Manero Guillermo , Grinblatt David L. , DeGutis Irene S. , Kiselev Pavel , McBride Ali , Heydendael Willem , Yu Edward , Roboz Gail J. 
Published: June 2023

7021 Background: For patients (pts) with AML, timely treatment is critical. The COVID-19 pandemic broadly disrupted healthcare (eg, decreased blood donations), possibly causing delays in AML treatment and care. To determine the extent of the COVID-19 impact on AML, this analysis examines the effect of the pandemic on managing pts with AML in the Connect Myeloid Registry (NCT01688011). Methods: The Registry is a large, US, multicenter, prospective, observational cohort study that includes newly diagnosed pts with AML aged ≥55 y. Pt characteristics (including assessment for transplant) were analyzed from December 2013 to March 2020 (from Registry opening to the start of the pandemic; Period 1), from March 2020 to May 2021 (during major healthcare disruptions; Period 2), and from May 2021 to January 2022 (resource stabilization and increased vaccine availability; Period 3). Monthly COVID-19 incidence was calculated per weekly US government data (CDC COVID Data Tracker; 2023). Rates of visits (office, remote) and transfusions were calculated by monthly events/person-year. Overall survival (OS) was estimated using the Kaplan-Meier method. Results: In this analysis, 650 pts were included in Period 1, 87 pts in Period 2, and 36 pts in Period 3; demographics and baseline characteristics were balanced across periods. Prior to the COVID-19 pandemic (Period 1), 25.1% of pts were not assessed for transplant; however, after the onset of the pandemic, this increased (45.5% and 44.4% in Periods 2 and 3, respectively). When monthly US COVID-19 cases increased, in-person visits and transfusion rates generally decreased in the Registry (Table). The proportion of pts receiving oral-containing induction regimens was 49.4% (40/81) in Period 1 (starting in January 2019, due to FDA approval of venetoclax in November 2018) and 50.6% (44/87) in Period 2, with a slight increase to 63.9% (23/36) in Period 3. No significant differences in OS by period were observed. Conclusions: In this analysis of pts with AML in the real-world setting, a pattern of increased COVID-19 cases in the US was accompanied by fewer transfusions, fewer in-person visits, and fewer assessments for stem cell transplantation, without a significant impact on OS. Clinical trial information: NCT01688011 . [Table: see text]
Examining safety and durable disease remission in R/R B-ALL after autologous CD19-directed CAR T cells produced by novel PRIMCAR manufacture platform.
Authors: Yang Zhi , Li Shiqi , Li Yu , Liu Lin , Yuan Zhongtao , Zhang Yingzi , Luo Le , Zhang Lihua , Chen Yingnian , Zhang Qianzhen , Shen Junjie , Li Yunyan , Wang Linling , Wang Meiling , Zhu Wei , He Xiao , Wang Youcheng , Dong Yancheng , Wang Sanbin , Qian Cheng 
Published: June 2023

7026 Background: CD19 chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy in the r/r B-ALL. However, the life-threatening side effect and disease relapse limited its wide application. To overcome these limitations, we established a novel PrimeCAR platform (PRIMCAR) and reported the preliminary safety and effectiveness data of MC-1-50 CAR-T cells before (Shiqi Li, et al. J Clin Oncol 2022; 40 [suppl 16]. Abstract 7008). Here, we present updated data. Methods: In this Phase I /II study (NCT04271410), MC-1-50 CAR T cells were manufactured by the PRIMCAR platform, which reduces manufacture periods to about 2 days. Patients (pts) received single-dose of MC-1-50 at dose ranged 1-5×105 CAR+/kg (Level 1, 1×105 CAR+/kg; Level 2, 2×105 CAR+/kg; Level 3, 3×105 CAR+/kg; Level 4, 5×105 CAR+/kg). Pts were pre-conditioned with fludarabine (25-30 mg/m2) and cyclophosphamide (200-300 mg/m2) daily for 3 days. Toxicity was graded by CTCAE, CRS and ICANS were graded by ASTCT criteria. Results: 19 pts with r/r B-ALL were infused. Disease characteristics and outcomes are shown in the table. No DLTs were reported. 18 pts (94.7%) experienced CRS, including 10 (52.6%) at grade 1, 7 (36.8%) at grade 2, 1 (5.3%) at grade 3, and no ≥ 4 CRS were observed. Three pts (15.8%) experienced ICANS, including 2 (10.5%) at grade 1, 1(5.3%) at grade 2, and no ≥ 3 ICANS occurred. All patients achieved CR/CRi (BM MRD-) in the first month. All patients received no other anti-tumor therapy until relapse was confirmed. The median DOR was not reached. 6 patients confirmed relapse, including 4 were CD19 negative and 2 were CD19 positive but with CD19 gene mutation at the time of relapse. All patients in 4 dose levels had good CAR-T expansion and exhibited long persistence features. Only 3 patients experienced the loss of CAR-T. Conclusions: Treatment of r/r B-ALL at a very low dose resulted in excellent safety profiles while exhibiting a high and durable efficacy. That makes this PRIMCAR platform potential for outpatient administration in the future. Clinical trial information: NCT04271410 . [Table: see text]
Survival outcomes with CPX-351 vs 7+3 by baseline bone marrow blast percentage in older adults with newly diagnosed high-risk or secondary acute myeloid leukemia: A 5-year follow-up study.
Authors: Ritchie Ellen K. , Lin Tara L. , Newell Laura F. , Stuart Robert K. , Solomon Scott R. , Stone Richard M. , Schiller Gary J. , Wieduwilt Matthew Joseph , Ryan Eileen A. , Dronamraju Nalina , Lancet Jeffrey E. , Cortes Jorge E. 
Published: June 2023

7027 Background: CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, is approved for newly diagnosed therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes in the US and Europe following positive efficacy and safety data from the pivotal phase 3 clinical trial (NCT01696084). A previous exploratory analysis of the trial data (median follow-up 20.7 months) showed improved survival outcomes with CPX-351 vs conventional 7+3 chemotherapy in adults with newly diagnosed high-risk or secondary AML (sAML) irrespective of baseline bone marrow (BM) blast percentage. Here we report 5-year follow-up data (median follow-up 60.9 months) to provide insights into the longer-term efficacy and safety of CPX-351 in these patient subgroups. Methods: Patients (60–75 years) with a pathologic diagnosis of AML (high-risk/sAML) per the WHO 2008 criteria (≥20% blasts in peripheral blood or BM) and an ECOG PS of 0–2 were randomized to receive CPX-351 or 7+3 chemotherapy. In these post hoc subgroup analyses at 5 years follow-up, overall survival (OS), event-free survival (EFS) and complete remission (CR) were assessed by baseline BM blast percentage. The analysis included patients with low ( < 20%) BM blasts to account for changes in blast count thresholds in the updated WHO AML classification. Results: Overall, median OS and EFS were longer with CPX-351 vs 7+3 in each subgroup; median OS was greatest in low blast subgroups for both treatments (Table). Higher CR rates were observed with CPX-351 vs 7+3 irrespective of baseline BM blasts. Median Kaplan-Meier (KM)-estimated survival rates increased with CPX-351 vs 7+3 across BM blast subgroups. The CPX-351 safety profile was comparable across BM blast subgroups and consistent with the known safety profile of 7+3. Conclusions: These 5-year follow-up data suggest that CPX-351 results in improved outcomes irrespective of baseline BM blast percentage vs conventional 7+3 chemotherapy in older adults with AML. Clinical trial information: NCT01696084 . [Table: see text]