bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of bemcentinib (BGB324), a first-in-class highly selective AXL inhibitor, with pembrolizumab in pts with advanced NSCLC: OS for stage I and preliminary stage II efficacy.
Authors: Felip Enriqueta , Brunsvig Paal , Vinolas Nuria , Ponce Aix Santiago , Carcereny Costa Enric , Dómine Gomez Manuel , Trigo Perez Jose Manuel , Arriola Edurne , Campelo Rosario Garcia , Spicer James F. , Thompson Jonathan Robert , Ortega Granados Ana Laura , Holt Robert J , Lorens Katherine , Lorens James B. , Shoaib Muhammad , Siddiqui Abdul , Schmidt Emmett V. , Chisamore Michael Jon , Krebs Matthew 
Published: March 2020

9098 Background: AXL is an RTK implicated in epithelial-to-mesenchymal transition and as a resistance mechanism to multiple therapies including anti-PD1. Bemcentinib (BGB324) is a first-in-class, oral, highly selective and potent AXL inhibitor which has been demonstrated to enhance anti-PD1 therapy in the pre-clinical setting. Methods: This is a Phase II single-arm, two-Stage study with bemcentinib (200mg/d) and pembrolizumab (200 mg/q3wk) for previously treated, IO naïve pts (n = 48 in total) with Stage IV lung adenocarcinoma. The primary endpoint was ORR according to RECIST 1.1 with pre-defined minimum requirement for 18% RR in the first Stage (n = 24) to proceed to Stage 2. Secondary endpoints included DCR, PFS, OS and safety. Tumour biopsies were analysed for PD-L1 (22C3 pharmDx), AXL, and infiltrating immune cells. Results: Stage 1 completed enrolment in Apr ‘18. As of Feb ‘19, 38 pts (24 and 14 in Stage 1 and 2, respectively) have been dosed with the combination; median age 66 (range 39-79) yr, 59% male, all previously received one prior line of platinum-based chemotherapy or a licensed EGFR/ALK-directed therapy. The most common TRAEs (occurring in > 15% of pts) were transaminase increases (37%), diarrhoea (29%), and asthenia (17%). All cases of transaminase increase were reversible and resolved with concomitant administration of systemic corticosteroids and interruption of study treatments. At time of writing, Stage 1 had met the efficacy threshold to proceed to Stage 2 with continued enrolment. Among 29 pts evaluable for response 7 PRs were reported (24%). For AXL positive pts (10/21 with available biopsies), ORR was 40%. PD-L1 status was known for 5 responders: 4 pts (80%) were PD-L1 negative or weakly positive. In Stage 1, mPFS was 4.0 months (95% CI 1.9 – NR) and 5.9 months in AXL positive pts (n = 10; 3.0 - NR). mOS was not mature. Conclusions: Overall, bemcentinib in combination with pembrolizumab was well tolerated and promising clinical activity was seen, particularly in pts with AXL positive disease. Updated results will be reported at the meeting, incl 12-month OS for Stage 1 and preliminary efficacy of Stage 2. Clinical trial information: NCT03184571.
Immune-checkpoints inhibitors in metastatic non small cell lung cancer with rare histology.
Authors: Signorelli Diego , Ferrara Roberto , Proto Claudia , Lo Russo Giuseppe , Imbimbo Martina , Galli Giulia , De Toma Alessandro , Pagani Filippo , Randon Giovanni , Fucà Giovanni , Trevisan Benedetta , Ganzinelli Monica , Zilembo Nicoletta , Fabbri Alessandra , De Braud Filippo G. , Garassino Marina Chiara , Prelaj Arsela 
Published: March 2020

9106 Background: Immune-checkpoints inhibitors (ICIs) have clearly improved prognosis of metastatic lung squamous carcinoma and adenocarcinoma, while their benefit remains uncertain in patients (pts) with rare NSCLC histotypes (RH). The study aim was to evaluate ICIs efficacy in RH. Methods: We retrospectively collected data from consecutive metastatic NSCLC pts treated with ICIs at our Institution from 4/2013 to 12/2018. Objective response rate (ORR) and disease control rate (DCR) were assessed. Fisher’s exact test was used to compare ORR and DCR in RH versus not-RH (NRH). Univariate and multivariate survival analyses were estimated by Kaplan-Meier and Cox progression hazard models. Results: Of 268 pts, 31 (11.6%) had RH: 16 sarcomatoid, 7 pulmonary enteric adenocarcinoma, 4 large cell neuroendocrine carcinoma and 4 adenosquamous carcinoma. In RH group, median age was 67 years old (range 41-81), most were males (71%) and smokers (90.3%); ECOG PS was: 0 (16.1%), 1 (67.8%) and 2 (16.1%). PD-L1 < 1%, 1-49%, ≥50% and unknown expression were reported in 22.6%, 19.3%, 35.5% and 22.6% pts, respectively. Twelve pts received ICIs as first and 19 as second or further-line. ORR was 22.6% in RH, 20.3% in NRH (p = 0.81); DCR was 35.5% in RH, 53.1% in NRH (p = 0.08). After a median follow-up of 20 months (m) (95% CI 4.0 – 36.7 m), median progression-free survival (PFS) was 2.6 m (95% CI 1.9-3.3 m) in RH vs 2.6 m in NRH (95% CI 2.1 – 3.0 m); median overall survival (OS) was 4.6 m (95% CI 0.03-12.0 m) in RH vs 9.2 m (95% CI 7.4 – 10.9 m) in NRH. No statistically significant differences were seen between the two groups (p = 0.729 for PFS, p = 0.601 for OS). At multivariate analyses adjusted for age, sex, smoke, PS, PD-L1 status, line of therapy and histotype (RH vs NRH), only low PS and first line treatment showed better PFS and OS (p < 0.001 and p = 0.003, respectively) in overall population. Conclusions: Our analysis, limited by the small and heterogeneous RH sample size, reported no significant differences between RH and NRH in terms of ORR, DCR and survival. However, looking at OS and DCR data, RH seem to have worse outcome. Correlation between histotype and pts characteristics and survival analyses in a larger cohort of ICIs treated NSCLC pts is ongoing. Specific prospective trials are needed to evaluate ICIs role in RH.
Fast-progression (FP), hyper-progression (HPD) and early deaths (ED) in advanced non-small cell lung cancer (NSCLC) patients (pts) upon PD-(L)-1 blockade (IO).
Authors: Ferrara Roberto , Mezquita Laura , Texier Matthieu , Lahmar Jihene , Audigier-Valette Clarisse , Tessonnier Laurent , Mazieres Julien , Brosseau Solenn , Leroy Laura , Duchemann Boris , Lefebvre Corentin , Veillon Remi , Westeel Virginie , Champiat Stephane , Planchard David , Remon Jordi , Gazzah Anas , Soria Jean-Charles , Caramella Caroline , Besse Benjamin 
Published: March 2020

9107 Background: HPD was described in 13.8% of NSCLC pts upon single-agent IO and correlated with high metastatic burden and poor prognosis. Other progression (PD) patterns as FP and ED within 12 weeks have been reported respectively in 4.7% and 5.6% of atezolizumab treated NSCLC pts. Whether FP/ED and HPD are different or overlapping patterns is currently unknown. Methods: We analyzed FP, ED and HPD in a multicentric (8 centers) retrospective cohort of IO treated NSCLC pts (11/2012-04/2017). Eligibility criteria required 2 CT scans before and one after IO start. HPD was defined as RECIST v 1.1 PD at first CT scan and a variation per month of tumor growth rate (TGR upon IO – TGR before IO) > 50%. ED was defined as deaths due to disease PD within 12 wks of IO start. FP was defined as ≥ 50% increase in the sum of long diameters within 6 weeks (wks) from baseline. The associations between PD patterns and pts’ characteristics were performed using Fisher or t-student tests. Median overall survival (mOS) was estimated by Kaplan-Meier method and compared by log-rank test. Results: Out of 406 NSCLC pts, 46% were ≥65 years, 72% had non-squamous NSCLC, > 90% received single agent IO in ≥2 line. 56 (13.8%) were HPD by TGR analysis. Among 72 pts (18%) who performed a CT scan within 6 wks after IO start, 6 (8.3%) were FP. These 6 FP pts were also classified as HPD by TGR analysis, while the other 50 (89%) of 56 HPD pts were not FP. The rate of PD in ≥ 3 sites (54% vs 0%, p = 0.002), the rate of liver PD (62% vs 5%, p = 0.002), the baseline tumor burden (BTB) (mean 176± 26 mm vs 55 ± 6 mm, p < 0.0001) and the TGR upon IO (mean 439± 119% vs 216 ± 41%, p = 0.03) were significantly higher in FP pts compared to HPD pts who were not FP. At 4.4 months of median follow-up, FP pts had significantly worse mOS compared to HPD pts not FP [0.7 months (95% CI 0.6,0.8) vs 1.6 months (95% CI 1.1, 2.1); p = 0.02]. Of 406 IO treated pts, 46 (11%) were ED within 12 wks, and 21 (46%) of ED pts had also HPD by TGR analysis. Conclusions: FP and ED are not a surrogate of HPD. FP occurs in a small subgroup (11%) of HPD and correlates with more aggressive features (PD in ≥3 sites, liver-PD, high BTB, high TGR upon IO) and worse OS. ED within 12 wks overlapped with HPD for only 46% of pts.
Treatment with FLAG followed by second allogeneic stem cell transplant for relapsed acute myeloid leukemia and myelodysplastic syndrome.
Authors: Pham Brian , Hoeg Rasmus , Hariharan Nisha , Alvarez Kathyryn , Rosenberg Aaron Seth , Jonas Brian Andrew , Tuscano Joseph M. , Abedi Mehrdad 
Published: March 2020

e18503 Background: There is no standard treatment for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) relapsing after allogeneic stem cell transplant (SCT). Options include combination chemotherapy, withdrawal of immunosuppression, donor lymphocyte infusion (DLI), and second SCT. Previous studies have used fludarabine, cytarabine, and granulocyte colony stimulating factor (FLAG) or second SCT separately for salvage therapy. Our institution uses FLAG followed by SCT from the same donor (FLAG/SCT) in this setting. We report a retrospective study of FLAG/SCT in MDS and AML patients relapsed after SCT. Methods: Patients who received FLAG/SCT for treatment of relapsed AML or MDS between 2009 and 2018 were identified using the bone marrow transplant database at University of California Davis. Their baseline characteristics and outcomes were determined using the electronic medical record. Descriptive statistics and Kaplan-Meier survival analysis were used to describe patients, rates of graft-versus-host disease (GvHD) and estimate survival times. Results: Nineteen patients received FLAG/SCT for AML (n=18) and MDS (n=1). Median time to relapse from first SCT was 145 days (range 41 to 960 days). Prior to FLAG/SCT, 17 patients had medullary relapse (median bone marrow blasts 27%; range 7-85%). Two patients had extramedullary relapse. Eighteen (94.7%) patients achieved complete remission (CR) after FLAG/SCT. Median follow-up time was 354 days from the first day of FLAG/SCT (range 7 to 2144 days). Six patients (31.6%) relapsed with median time to relapse of 334 days (range 78 to 679 days) after treatment. Overall survival at 2 years was 52.5%. Causes of death were relapsed AML (n=4; 21.1%), infection (n=4; 21.1%) complications of GvHD (n=3,15.8 %), and brain herniation (n=1, 5.3%). Acute GvHD grade I-IV and new onset chronic GvHD occurred in thirteen (68.4%) and eight patients (42.1%), respectively. Conclusions: FLAG/SCT for AML and MDS relapsing after SCT resulted in a high remission rate. The overall survival of over two years suggests that the second SCT augmented the graft versus leukemia effect. The GvHD rate increased after second SCT, but the rate and severity were manageable. FLAG/ SCT is a reasonable option for relapsed AML and MDS after SCT.
Clinical value of event-free survival (EFS) in acute myeloid leukemia (AML).
Authors: Maiti Abhishek , Kantarjian Hagop M. , Popat Vinita , Blanco Carlos , Velasquez Miguel , Garcia-Manero Guillermo , Konopleva Marina , Verstovsek Srdan , Andreeff Michael , Borthakur Gautam , Kadia Tapan M. , Daver Naval Guastad , Pemmaraju Naveen , Dinardo Courtney Denton , Pierce Sherry A. , Wierda William G. , Kornblau Steven Mitchell , Ravandi Farhad , Cortes Jorge E. 
Published: March 2020

e18513 Background: EFS is not considered a robust end-point for AML trials. We hypothesized that rather than a surrogate for overall survival (OS), improvement in EFS may be valuable due to patients (pts) staying in remission and thus decreasing health care utilization (HCU). Methods: In this retrospective study we identified AML pts treated on frontline therapy trials at our institute from 2003-2013 with EFS ≥2 months (mo) and OS of 12-36 mo. We captured the amount of HCU from diagnosis till death, including number of clinic and emergency room (ER) visits, hospitalizations, consultations, blood product transfusions, invasive procedures, laboratory and imaging studies. Linear regression and product-moment correlation were used to determine the relation between these parameters and EFS. Results: Among 337 pts meeting inclusion criteria, the median age was 65 years, 30% had adverse risk AML, 47% received intensive chemotherapy (IC) and 27% received hypomethylating agents (HMA). The median EFS was 10.8 mo. Increasing EFS led to statistically significant decline in HCU for all patients regardless of OS and the correlations were stronger for pts achieving a complete remission (CR, Table). These observations held true across European LeukemiaNet risk groups, younger and older pts, and those receiving IC, HMA, and non-IC, with or without other agents. Conclusions: In newly diagnosed AML, improvement in EFS is correlated with decrease in all HCU irrespective of OS duration. [Table: see text]
Timed sequential therapy with high-dose cytarabine and mitoxantrone as an induction regimen for acute myeloid leukemia: An update on adverse events.
Authors: Richardson Kristin J. , Kollipara Revathi , Katz Deborah Ann , Hoyt Maura , Gallas Kirstin , Venugopal Parameswaran , Larson Melissa L. 
Published: March 2020

e18524 Background: Traditionally, patients eligible for induction chemotherapy for AML are treated with the “7+3” regimen, standard doses of infusional cytarabine and an anthracycline, with historical CR rates of 50-60%. We present a retrospective analysis of an alternate induction regimen. Based on timed sequential therapy, it consists of a 2-day treatment with high dose cytarabine, which improves remission rates when used in induction, and dose intensified anthracycline therapy, which improves outcomes while maintaining an acceptable safety profile. Methods: 200 patients were treated from 2010-2015. Patients received 2 doses of cytarabine 2 gm/m2 (1.5 gm/m2 age > 70 years) IVPB over 3 hours, 12 hours apart followed by 1 dose of mitoxantrone 30 mg/m2 IVPB over 1 hour on days 1 and 5. Cytogenetics and adverse events data were collected. IWG remission criteria were used to determine remission status. Results: Median age 57.6 years (range 23-79); 105 (53%) age > 60. 119 male; 81 female. Risk stratification: 12 favorable; 108 intermediate; 80 unfavorable . Overall CR rate (CRR: CR+CRi+CRp) for all patients was 68.5%. CR rates based on risk karyotypes: favorable 100%, intermediate 76.8%, unfavorable 52.5%. Most common G3-4 adverse events: anemia (60% G3, 40% G4), neutropenia (1% G3, 99% G4), thrombocytopenia (0.5% G1, 99.5% G4). 196 patients (98%) had neutropenic fever; 134 (67%) documented infections (100 with G3/4), 62 (31%) neutropenic fever with no source. 52 (26%) experienced bleeding (15 G1, 31 G2, 4 G3, 1 G4, 1 G5). G3/4 renal or hepatic toxicity was rare. No cerebellar toxicity occurred during induction. 30 day mortality 0.5%; 60 day mortality 3%. 62 (31%) patients are still alive; 122 died, 16 lost to follow-up. Conclusions: This two-day induction regimen is an effective treatment for AML with an acceptable safety profile including patients age >60. There is a high response rate, particularly for favorable and intermediate risk karyotypes, with a low rate of early mortality. The high response rates and tolerability with this regimen provides a platform for further clinical trials to enhance outcome by combining with novel targeted therapies for AML.
Mortality of acute promyelocytic leukemia in a rural tertiary care center.
Authors: Vadakara Joseph , Kharel Prakash , Bhattacharya Prianka , Vanenkevort Erin , Manikowski Jesse 
Published: March 2020

e18529 Background: Acute promyelocytic leukemia (APL) has a very good prognosis when diagnosed and treated promptly. Despite the excellent prognosis, early mortality remains high, ranging 17-40%. Geisinger Health System (GHS) has provided treatment for a significant number of APL patients, but mortality of APL at GHS has not been studied. We conducted a study to assess early mortality related to APL in GHS. Methods: Retrospective analysis was performed of patients diagnosed with APL from January 1988 to February 2019, determining the number of patients diagnosed and treated for APL in GHS, overall 30-day mortality rate, stratified by risk group (low, intermediate, high based on presenting white blood cell and platelet counts) and age above or below 55. Results: A total of 61 patients with APL were identified. Average age at diagnosis was 44.77 years (SD = 19.12). The death rates in patients in whom risk data was available was 7%, 9.3% and 11.6% respectively in the low, intermediate and high risk groups respectively. There was no statistically significant difference in the frequency distribution between risk categories for survival, χ2 = 1.03, p = .60. Between age groups, 8.3% of patients under age 55 died, whereas 18.3% of those 55 or older died. Survival between the two age groups was statistically significant, χ2 = 10.92, p = .001. Estimated 30-day overall mortality in the studied population was 16.39%; and 7.69%, 5.56% and 38.46% for the low, intermediate, high-risk patients respectively. Conclusions: Among patients diagnosed with APL in the GHS over the past 30 years, the early mortality rate has been comparable to reported mortality rates in centers around the world. Our study showed a statistically significant higher mortality rate in patients 55 years or older. Further study is planned to assess factors contributing to mortality and outcomes.
Effect of secure clinical messaging on chemotherapy adherence.
Authors: McLarty Sarah , Friend Kayla E , Chadha Neha , Verma Santosh K , Sawicki Christine , Johnson Kjel Andrew 
Published: March 2020

e18542 Background: Oncologists offer essential clinical information to patients face-to-face or by phone. Today, patients commonly prefer digital communication. To test the effectiveness of this in patients, we deployed proprietary secure messaging (SM) to communicate clinical messages to patients regarding prescribed oral chemotherapy in an effort to improve adherence. Methods: Chronic myelogenous leukemia (CML) patients receiving a tyrosine kinase inhibitor (TKI) were evaluated as two groups: a test group of patients starting therapy between Jan - Jun 2018 who received SM within 45 days therapy start who received SM refill reminders, adherence, condition management, laboratory testing reminders every 30 days, and information regarding side effects, versus a control group that included propensity matched patients initiating therapy between Jan - June 2017 and who received only non-clinical text message refill reminders within 45 days of therapy start. Adherence was compared 6 months after the initial prescription. Primary outcomes were medication possession ratio (MPR) (total day supply/ [(last fill date+last fill day supply)-first fill date]), number of prescriptions filled, % of patients optimally adherent (MPR ≥ 85%), and rate of discontinuation after first fill. The secondary outcome was days of therapy. A t-test evaluated MPR and length of therapy; logistic regression compared discontinuation after first fill and % optimally adherent. Results: 478 CML patients opted into SM and 478 where in the control group. MPR improved 1.6% absolute points (93.20 control v 94.80 test, p = 0.04); no change was seen in number of prescriptions filled (5.04 control v 5.17 test, p = 0.19). More patients receiving SM were optimally adherent (83.05 control v 88.31 test, p = 0.03); discontinuation after first fill was unchanged (6.90 control v 6.49 test, p = 0.79), as were days of therapy (156.51 control v 159.22 test), p = 0.35). Conclusions: Patients initiated on TKI therapy with receiving clinical SM had significantly higher adherence than the control group and were more likely to be optimally adherent, despite the high adherence rates of CML patients at baseline. Further analysis is needed to understand the durability of this adherence improvement.
Outcome of CML patients with de novo bleeding complications: Do they behave differently?
Authors: Sandal Rajeev , Jandial Aditya , Mishra Kundan , Prakash Gaurav , Khadwal Alka , Lad Deepesh , Varma Neelam , Malhotra Pankaj 
Published: March 2020

e18546 Background: Chronic myeloid leukemia (CML) is a clonal hematopoietic neoplasm. A subset of CML patients present may present with unusual bleeding manifestations. There is limited data on the incidence and outcome of such patients on treatment with imatinib. Methods: We analysed the CML patients treated at PGIMER Chandigarh from January 2003 to December 2018. Baseline spleen and liver size, hematological parameters, Sokal and Hasford score, site and severity of bleeding (as per WHO classification) were recorded. The treatment response, occurrence of cytopenias and need for second line TKI were analyzed. Results: Sixty-six patients (2.8%) out of 2350 adult CML patients had bleeding at diagnosis. The median age was 35 years (range 15 – 66 years); 56.1% were males. The median duration of follow up was 79 months (range 6 – 123 months). Splenomegaly and hepatomegaly was found in 89.3% and 65.1% patients, respectively. Baseline median hemoglobin was 9.5 g/dL; TLC was 151600/mm3 and platelet count was 301000/mm3. Based on Sokal score, 15/66, 26/66 and 25/66 patients belonged to low, intermediate and high risk categories, respectively. According to Hasford score, 22/66, 36/66 and 8/66 patients belonged to low, intermediate and high risk categories, respectively. Based on WHO grading, 33/66, 30/66 and 3/66 patients had grade 1, 2 and 3 bleed, respectively. 48 patients had mucocutaneous bleeding [cutaneous 17, gum bleed 16, epistaxis 15], 4 had psoas haematoma, 7 had vaginal bleeding, 3 had ocular bleeding, 6 had GI bleed [upper GI 3, lower GI 3], 3 had hematuria. 74.2% achieved CHR at 6 weeks and 83.3% achieved MMR at 12 months with Imatinib. 18 developed cytopenias which required Imatinib interruption or dose reduction. 18 required Imatinib dose escalation for suboptimal response, 5 patients received second line TKI. Six patients progressed to advanced phase CML (AP/BC) after a median duration of 32 months (range 21 – 49 months). Bleeding manifestations resolved in all patients and there was no recurrence of bleeding on follow up. Conclusions: Bleeding is an uncommon presentation of CML. It might be a harbinger of an increased risk of cytopenias, suboptimal treatment response and disease progression on Imatinib.