bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world characteristics and outcomes of patients with advanced non-small cell lung cancer (aNSCLC) receiving immune checkpoint inhibitor.
Authors: Khozin Sean , Zhi Jizu , Jun Monika , Chen Li , Rubinstein Wendy S. , Walker Mark S. , Komatsoulis George Anthony , Roberts Jeremy , Fukushima Ryan , Lau Denise , Hyde Brigham , Stepanski Edward , Miller Robert S. 
Published: March 2020

9110 Background: Immune Checkpoint Inhibitors (ICIs) were first approved for the treatment of aNSCLC in 2014, and since this time have seen rapid adoption in the marketplace. We sought to describe the characteristics of patients with aNSCLC receiving ICIs in the real-world, as well as to examine treatment patterns and outcomes in the time since initial ICI approval. Methods: We conducted a retrospective, observational cohort study using statistically de-identified data from January 2011 to November 2018 in CancerLinQ, ASCO’s real-world oncology database. Adult patients with a curated diagnosis of Stage III or IV NSCLC who received ≥1 dose of an ICI and had ≥2 clinical visits were eligible for inclusion. Stage III patients were excluded if they received any local therapy < 1 year prior to receiving ICI. Patients were also excluded if they received ICI prior to the first FDA approval date. Demographic and clinical characteristics of aNSCLC patients receiving ICI are reported. Outcomes including time to treatment discontinuation (TTD), time to next treatment (TTNT), real-world progression free survival (rwPFS) and overall survival (OS) were examined via the Kaplan Meier method. Results: Among 2,425 aNSCLC ICI patients included in this analysis, median age was 68.0 years (IQR 60.7, 75.2], 54% were male and 73% of patients were white. Non-squamous histology accounted for 64% of aNSCLC ICI users, and 81% had Stage IV disease. Eastern Cooperative Oncology Group (ECOG) performance status was 0-1 in 77% and 2+ in 23% of patients, and 70% were current or former smokers. The majority (75%) of patients received ICI as second-line or later therapy. Treatment outcomes and survival are reported in the Table. Conclusions: This analysis demonstrates that aNSCLC patients receiving ICI therapy in the real-world are older than what was reported in some clinical trials, though survival outcomes were similar. Further research to examine impact of covariates on outcomes is warranted. [Table: see text]
A retrospective, real-world population-based analysis of treatment patterns and outcomes in adult patients with relapsed/refractory acute myeloid leukemia in Alberta, Canada.
Authors: Geddes Michelle N. , Saini Lalit , Liu Fei Fei , Yusuf Dimas , Schwann Kiersten , Billawala Alkarim , Kurniawan Jessica A. , Cheung Winson Y. , Brandwein Joseph M. 
Published: March 2020

e18505 Background: In order to describe the impact of future targeted therapies on treatment outcomes of patients (pts) with relapsed and/or refractory (RR) acute myeloid leukemia (AML), a better understanding of the clinical management pathway in these pts is needed. We therefore evaluated the treatment patterns and associated outcomes in a real-world cohort of pts with RR-AML using a population-based cancer registry and patient medical records. Methods: Pts newly diagnosed wih AML between January 2013 and December 2016, aged ≥ 18 years were identified from the provincial-wide Alberta Cancer Registry (ACR). Data for pts who met the criteria for RR-AML were assessed by hematologists and were extracted from medical records. RR-AML pts were then categorized as: receiving intensive therapy (IT); receiving non-intensive therapy (NIT); or treated with best-supportive care (BSC) following a diagnosis of RR-AML. Results: 572 AML pts were identified from the ACR, of which 199 met criteria for RR-AML and were included in the analysis (124 males, 75 females; median age at diagnosis of RR-AML 66.8 years; median follow-up 4.7 months). In this RR-AML cohort, 26 (13%) pts received ≥ 2 lines of prior therapy. Unadjusted median overall survival (mOS) was 5.3 months, with a 12-month overall survival rate of 29.6% (95% CI 29.0–30.3%) from the time of RR. Following RR, 46 (23%) pts received IT, 65 (33%) pts were treated with NIT, and 88 (44%) pts received BSC, with unadjusted mOS of 13.8, 9.4, and 2.1 months, respectively ( P < 0.001). When stratified by European LeukemiaNet risk classification at diagnosis, unadjusted mOS was 12.4, 4.7, and 4.0 months for favorable risk, intermediate risk, and adverse risk groups, respectively ( P < 0.01). Conclusions: This retrospective, real-world study in Alberta Canada confirms the poor prognosis reported to date in the RR-AML population. Notably, a large proportion of pts received BSC which was associated with dismal survival outcomes. These data also highlight that effective and tolerable alternatives to current treatment options are urgently needed.
Safety and feasibility of outpatient high-dose cytarabine (HIDAC) and intermediate-dose cytarabine (IDAC) for consolidation therapy in acute myeloid leukemia (AML).
Authors: Li Wenhui , Simondsen Katherine , Lee Jamie , Elharake Maher , Kubal Timothy Edward 
Published: March 2020

e18509 Background: Patients with acute myeloid leukemia (AML) who achieve complete remission with induction therapy require consolidation therapy. The standard of care consolidation is HIDAC or IDAC depending on age and risk stratification. Consolidation therapy has historically been administered in the inpatient setting. The rising cost of AML care has prompted institutions to consider shifting therapy to the outpatient setting. However, the safety and feasibility of outpatient HIDAC/IDAC consolidation therapy has not been established. Moffitt Cancer Center (MCC) developed an Inpatient/Outpatient (IPOP) program to facilitate administration of complicated regimens in the outpatient setting. We hypothesized that IPOP administration of HIDAC/IDAC consolidation therapy is safe and may have cost-savings implications. Methods: We conducted a retrospective chart review on AML patients who were 18 years or older and received HIDAC/IDAC consolidation therapy at MCC following induction therapy from January 1, 2015 to November 1, 2018. Data collected included age, risk stratification, treatment history, clinic visits, number of cycles received in the IPOP versus inpatient setting, supportive care, hospitalizations, and chemotherapy related adverse events. Results: 258 of 270 cycles of HIDAC/IDAC were delivered outpatient over the reviewed time period to 122 patients. 45 patients (37%) required hospitalization during consolidation with the primary reason being neutropenic fever (72%), consistent with historical data (50 to 90%). No patients receiving outpatient consolidation required hospitalization during chemotherapy. Specific details regarding administration of HIDAC/IDAC in IPOP, including infusion times, frequency of visits, laboratory frequency, supportive medications, and home antimicrobials will be reported. 1,290 hospital days were saved through IPOP administration. Financial assessment of cost-savings is being determined and will be reported. Conclusions: Outpatient administration of HIDAC/IDAC consolidation therapy for AML is a safe option for AML patients undergoing consolidation.
The prognosis of NF1 mutations in newly diagnosed AML: A single-center retrospective study.
Authors: Telfah Mohammad , Abdelhakim Haitham , Balmaceda Nicole , Gharaibeh Eyad , Godwin Andrew K. , Pessetto Ziyan Y. , McGuirk Joseph , Lin Tara L. 
Published: March 2020

e18525 Background: Several recurrent genetic mutations have been described in acute myeloid leukemia (AML), which have both prognostic and therapeutic implications. Recurrent mutations in the Neurofibromin 1 ( NF1) gene are reported in 1-5 % of AML patients; however, there are limited data regarding its prognostic implications. Here, we report the outcomes for patients with newly diagnosed AML with a somatic NF1 mutation at our center. Methods: A retrospective chart review included patients with newly diagnosed AML at KUMC from 01/2016 through 09/2018. All patients had targeted next-generation sequencing (NGS) at diagnosis. Baseline characteristics were compared between patients with NF1 mutations and those who were wild-type using Fisher’s exact test for categorical variables, and the Wilcoxon rank-sum test for continuous variables. The primary outcome was overall survival (OS), which was measured from the time of diagnosis to the time of death from any cause. A stepwise Cox proportional-hazard model was used to adjust for potential confounders. Results: Data on 110 patients were included. Out of the 110 patients, 15 (13.6%) had a delectable NF1 mutation, while 95 (86.4%) patients were NF1 wild-type. The baseline characteristics of the two groups are displayed below. Median OS for patients with an NF1 mutation was 7.3 months, while it was 18.4 months for patients with NF1 wild-type, Log-rank test p-value 0.02. After adjusting for potential confounders, including age, ELN risk category, induction regimen, presence of other mutations such as TP53, the hazard of death remained significantly higher for patients with NF1 mutations, HR 2.4, CI (1.05-5.6), p-value 0.04. Conclusions: In this single-center retrospective study, the presence of a NF1 mutation was associated with worse overall survival in patients with newly diagnosis AML. [Table: see text]
Analytical validation of a 47-gene NGS panel for molecular profiling of myeloid neoplasms.
Authors: Rosenthal Sun Hee , Gerasimova Anna , Li Hai-Rong , Qu Kevin , Acab Allan J , Chong Hansook K , Zhang Xi , Nguyen Quoclinh , Smolgovsky Alla , Wolfson David , Grupe Andrew , Elzinga Christopher , Chen Rebecca , Owen Renius , Catanese Joseph J , Racke Frederick KARL , Lacbawan Felicitas L. 
Published: March 2020

e18526 Background: Molecular profiling can help diagnose, classify, and guide treatment of myeloid neoplasms. Next generation sequencing (NGS) is a powerful platform that can facilitate identification of actionable genetic alterations in multiple genes simultaneously. To serve clinical management needs, we developed and validated a NGS panel for 47 genes associated with diagnostic, prognostic, and/or therapeutic utilities for each of the subclasses of myeloid neoplasms: acute myeloid leukemia (AML, 42 genes), myelodysplastic syndrome (MDS, 36 genes), and myeloproliferative neoplasms (MPN, 26 genes). Methods: A total of 154 unique de-identified specimens were analyzed. Intra- and inter-assay precision studies were performed by standard laboratory practice. Single nucleotide variations (SNVs), insertions/deletions (indels), and FLT3 partial tandem duplications (PTD) were assessed for the entire coding regions of 23 genes and targeted exons of 24 genes. Target regions were captured by hybridization with complementary biotinylated DNA baits, and NGS was performed on an Illumina NextSeq500 instrument. Sequence reads obtained were analyzed using a bioinformatics pipeline that was developed in-house. At least 500 unique reads with base quality (Q) ≥20 (99% confidence) were required for coverage QC, except targets on X chromosome for male specimens, which required 250 unique reads. Results: On average, each sample generated 13.2 million reads, 100% (SD = 0.2%) mapped reads to the reference sequence, 61.7% (SD = 8.8%) on-target reads, and 1,952 (SD = 873) mean coverage. Data using ≥Q20 unique coverage of all target regions across all validation samples demonstrated that all target regions, even in the extreme end of GC spectrum (range: 12%-87%), met coverage requirements. Intra- and inter-assay precision studies, using 7 and 21 specimens, respectively, resulted in 100% concordance among replicates. An accuracy study of 131 unique specimens (a subset of the 154 specimens) yielded in 99.6% (755/758, 95% CI: 99.4%-100%) concordance for variants with allele frequencies ≥5% in comparison to other molecular methods including Sanger sequencing. No reportable variants were detected from any normal specimens (n = 17). Conclusions: We developed and validated a NGS panel for 47 genes with diagnostic, prognostic, and/or therapeutic utilities for each of the subclasses of myeloid neoplasms: AML (42 genes), MDS (36 genes), and MPN (26 genes). This panel will allow simultaneous analysis of the 47 genes with high sensitivity and specificity and may help manage clinical needs.
Safety and efficacy of CPX-351 in younger patients < 60 years old with secondary acute myeloid leukemia: An updated analysis.
Authors: Przespolewski Amanda Cecile , Talati Chetasi , Fazal Salman , Vachhani Pankit , Sanikommu Srinivasa , Thota Swapna , Baron Jeffrey , Griffiths Elizabeth A. , Thompson James E. , Sweet Kendra Lynn , Wang Eunice S. 
Published: March 2020

e18530 Background: Patients (pts) with secondary acute myeloid leukemia (s-AML) have poor long-term outcomes following standard induction chemotherapy with 7+3. In 2017 CPX-351 was FDA approved for upfront treatment of s-AML. The phase 3 trial demonstrated improved overall survival in pts aged 60-75 years old. Although CPX-351 treatment is indicated in all adults with s-AML, it is unclear whether CPX-351 is safe and effective in younger pts < 60 years. We sought to address this unanswered question by retrospective review of clinical experience since FDA approval. Methods: Medical records were retrospectively reviewed at five large academic centers to identify pts aged 18-59 years old with untreated s-AML, prior cytotoxic therapy, or AML-MRC treated with CPX-351 as induction therapy. Results: 30 pts with confirmed s-AML received CPX-351 therapy. Mean age was 53 years (range 23 – 59), 18 were male (60%). The majority (60%, N = 18) had AML-MRC, 7 (23%) had treatment-related AML (t-AML) and 6 (20%) had antecedent MDS. 6 pts had received prior HMA therapy. 19 pts had a complex karyotype (70%), and 4 patients were found to have a normal karyotype (15%). The most common molecular event was TP53 mutation observed in 10 pts (36%), followed by FLT3-ITD identified in 4 pts (14%). Overall response rate (CR/CRi/PR) was 46.7% with 5 CR (17.2%), 3 CRi (10.3%), and 6 PR (20.7%). The remaining pts (15/29, 51.7%) were non-responders. 8 pts have received an allogenic stem cell transplant. The most common AE was infection (80%, 24/30) with 4 clinically significant bleeding events. Thirty-day mortality was 13.3%, with 60-day mortality of 16.7%. Overall survival was 7 months (range 0.5 – 12.4 months), with mean follow up of 4.4 months. Conclusions: This multi-institutional retrospective analysis suggests that CPX-351 results in lower response rates (CR/CRi 27.6%) and shorter overall survival (7 mos) than reported in the recently published phase 3 trial in pts aged 60-75 years old. Potential explanations for this discrepancy include short follow up, small sample size, retrospective design, and the significant proportions of pts with complex karyotype and TP53 mutations. Historically, patients < 65 years old with s-AML have had a reported overall survival of approximately 7 months. Further investigation of this regimen in younger pts with s-AML as compared with 7+3 and other approaches is warranted.
A novel anti-CD19 chimeric T cell therapy platform ET019002 was safe and effective in inducing CR in blast crisis of CML: A case study.
Authors: He Pengcheng , Liu Hong , Liu Haibo , Li Qijing , Luo Mina , Feng Hui , Ye Kai , Nejadnik Bijan , Shi Bingyin , Liu Cheng 
Published: March 2020

e18540 Background: CML can progress to blast crisis in which the disease behaves like an acute leukemia. A novel chimeric T-cell therapy ET019002 is built upon Eureka Therapeutics ARTEMIS platform and co-expressed with an additional anti-CD19 scFv fused to the CD28 protein. ET019002 demonstrated superior preclinical anti-tumor activities to the classical anti-CD19 CAR-T cells. Herein we describe the first-in-human clinical study of ET019002 in a blast crisis of CML subject with T315I mutation, breast, skin, nasal sinus, liver, CNS involvement and heavily previous lines of therapy. Methods: The subject received infusions of ET019002 T cells at the dose of 1x106 receptor+ T cells/kg on Day 0, 66 and 122. The primary objective is safety and the secondary objectives include ET019002 T-cell engraftment and anti-tumor efficacy. Results: The subject developed a transient fever and chills with a maximum temperature of 40.2°C 4 days post the 1st infusion. Fever was resolved within 3 days after giving NSAIDs. No inflammatory cytokines except IL-6 were elevated during the study. IL-6 elevated 4 days post the 1st infusion, reached peak level at 507.18 pg/ml on Day 6 and decreased to 37 pg/ml on Day 8. This was not seen after the 2nd and the 3rd infusion. Lumps from breast and skin disappeared and the enlarged liver and spleen were back to normal size. Bone marrow biopsy at day 12 showed lymphoblast cells were significantly decreased from baseline of 38% to the level of 1%. The leukemic cells in cerebrospinal fluid were cleared on Day 14. The copy number of tumor-related fusion gene BCR-ABL/ABL was reduced from 1.489 x 100 to 3.942 x 10-5. However, 2 months post the 1st infusion, BCR-ABL/ABL rebounded to 3.795 x 10-4. The 2nd infusion showed no effect on the relapse of the leukemia in molecular level. The 3rd infusion resulted in CR which relapsed 1 month post the infusion. Flow cytometry analysis showed the loss of CD19 on the leukemic cells. Conclusions: Repeated infusion of autologous ET019002 was safe and achieved a three-month CR after the ET019002 T cells therapy, which could provide a window for the patient to receive curative therapies such as bridging allogeneic hematopoietic stem cells. Clinical trial information: NCT03642496.
Molecular prediction of chronic myeloid leukemia risk and resistance to imatinib.
Authors: Jankovic Radmila , Krivokuca Ana , Boljevic Ivana , Radulovic Sinisa , Cavic Milena 
Published: March 2020

e18543 Background: Chronic myeloid leukemia (CML) is characterized by the Bcr-Abl genetic translocation which leads to constitutive tyrosine kinase signaling. Treatment with tyrosine kinase inhibitors as imatinib eliminates CML cells, but resistance often occurs. No specific molecular risk factors or imatinib-resistance predictors have been validated so far, thus the aim of this study was to determine genetic factors that would allow for a better management of this disease. Methods: An age and gender matched case-control study of 57 CML patients and 63 healthy controls was performed. In vitro experiments were performed on K562 cells and an imatinib-resistant K562R cell line. CML patients were treated with imatinib and stratified into responders (complete molecular response after three months, CMR) and non-responders. RNA was isolated from blood leukocytes or cells and used for cDNA synthesis. Gene expression levels were evaluated by real-time PCR and the results analyzed using the delta-delta-Ct method. Differences in expression levels and their prognostic/predictive potentials were evaluated by t-test, linear regression analysis and receiver operating characteristics curve, with statistical significance set at p < 0.05. Results: In CML patients, the Bcl2 and IGF-1R mRNA expression level were higher than in controls (1.03 ± 0.06 vs. 0.92 ± 0.18, p < 0.0001; 1.14 ± 0.15 vs. 1.03 ± 0.15, p = 0.0001, respectively). Prior to treatment, the Bcl2 mRNA levels were lower for the K562 than for the resistant K562R cell line (1.13±0.04 vs. 1.62±0.01, p < 0.0001), and the same was observed for IGF-1R (1.22±0.01 vs. 1.29±0.01, p = 0.001). Patients who achieved a CMR after imatinib treatment had significantly lower pre-treatment levels of Bcl-2 and IGF-1R (0.99 ± 0.05 vs. 1.04 ± 0.06, p = 0.005; 1.12 ± 0.02 vs. 1.15 ± 0.04, p = 0.0123, respectively) compared to patients who did not achieve a CMR, which confirmed the in vitro observed data. Conclusions: High levels of Bcl-2 and IGF-1R mRNA were detected in CML patients, and the analysis of their expression might be used as a low-cost CML screening tool. Successful imatinib treatment was correlated with significantly lower pre-treatment Bcl-2 and IGF-1R levels in vitro and in vivo, which might also be used as a low-cost molecular predictor of a favorable clinical response .
Admissions for neutropenic fever in myelodysplastic syndromes (MDS).
Authors: Ali Ambreen Fatima , Gerds Aaron Thomas , Advani Anjali S. , Mukherjee Sudipto , Sobecks Ronald M. , Sekeres Mikkael A. , Hamilton Betty Ky , Jha Babal , Hilton Cameron Beau , Kerr Cassandra M. , Adema Vera , Waldron Madeline , Siebenaller Caitlin , Nagata Yasunobu , Maciejewski Jaroslaw P. , Nazha Aziz 
Published: March 2020

e18548 Background: MDS are associated with a risk of severe infections due to disease course, patient (pt) age, co-morbidities and treatment. While infection rates have been reported for MDS patients enrolled in clinical trials, the real-world incidence of infections that require hospitalization, and how disease related factors (e.g. genetic mutations) affect the likelihood of infection remain unclear. Methods: Clinical data for MDS pts (per 2016 WHO criteria) diagnosed between 1/2010-12/2016, and treated at the Cleveland Clinic were included. TET2 mutation data obtained by NGS (in the context of genomic panel) was also included. Results: Our dataset included 214 pts of median age 70 years (range 13-99), with 33%, 54%, and 12% having low, intermediate, and high risk MDS according to IPSS-R. Overall, 100 admissions for neutropenic fever were recorded with a median length of stay of 5 days per admission; 63 (29%) pts required at least one admission, and of these 9 (14%) pts required 3 or more (up to 6) admissions. Blood cultures were positive in 17 (27%) pts with common organisms including Staphylococcus (38%), Enterococcus (35%), and Pseudomonas (12%). Urine cultures were positive in 6 (10%) pts, with organisms including E. Coli (50%), Pseudomonas (17%) and Klebsiella (17%). Fungal work up was sent in 18 (29%) pts and was positive in 3 (17%) pts. 13 (21%) pts required ICU transfer, and of those 7 (51%) pts required vasopressor support, and 10 (77%) pts required mechanical ventilation. Median ICU length of stay was 3 days (range 1-26). 13 (21%) pts were discharged on IV antibiotics. Median OS for the entire cohort was 18 months (95% CI 7.9 – 34.7), and median OS for admitted patients was not significantly shorter at 48 or 65 months. The number of admissions for neutropenic fever, length of stay, IPSS-R risk category, TET2 mutation, and ICU transfer did not impact survival. Conclusions: The risk of admission for neutropenic fever was 29% with blood cultures positive in 27% of pts. TET2 mutation status and IPSS-R risk did not impact admission rate, length of stay or ICU transfer.