bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of hypomethylating agent discontinuation among patients with higher-risk myelodysplastic syndromes.
Authors: Zeidan Amer Methqal , Joshi Namita , Kale Hrishikesh , Wang Wei-Jhih , Corman Shelby , Hill Kala , Salimi Tehseen , Epstein Robert S. 
Published: June 2021

7043 Background: Real-world studies have shown that persistence with intravenous (IV) and subcutaneous (SC) hypomethylating agents (HMAs) among patients (pts) with higher-risk myelodysplastic syndromes (MDS) is poor, with over one-third of treated pts receiving <4 cycles or having a ≥90-day gap in therapy, despite recommendations for at least 4-6 cycles to elicit response in absence of progression/unacceptable toxicity. Survival outcomes have also been shown to be worse, and direct medical costs higher, among HMA non-persistent vs persistent pts. We explored factors associated with early discontinuation of HMA therapy in this population. Methods: This was a retrospective cohort study among pts from the 2010-2016 SEER-Medicare linked database with a diagnosis of refractory anemia with excess blasts (RAEB; a surrogate for higher-risk MDS) from 2011-2015. Included pts had to have received HMA therapy and have ≥12 months’ continuous follow-up after diagnosis. Discontinuation was defined as stopping HMA therapy before 4 cycles. Multivariable logistic regression was used to assess predictors of HMA discontinuation. Results: In total, 664 pts with RAEB and treated with HMAs were included. Overall, 193 (29%) discontinued before 4 cycles; of these, 91 (47%) discontinued after 1 cycle, 57 (30%) 2 cycles, and 45 (23%) 3 cycles. Compared with pts continuing for ≥4 cycles, pts discontinuing before 4 cycles were generally older and more likely to be single/separated/divorced/widowed, have more comorbidities, and have poor performance status (PS) (Table). These trends were most pronounced among pts discontinuing HMA therapy after only 1 cycle vs ≥4 cycles (Table). In multivariable analysis, age 71-75 vs ≥80 y (odds ratio [OR] 0.556, p=0.017) and poor PS (OR 1.585, p=0.019) remained significant predictors of HMA discontinuation. Among treatment-related factors, the most statistically significant association with HMA discontinuation was observed for GCSF use (OR 0.453, p<0.001). Number of pills/day was not a predictor of HMA discontinuation (OR 1.009, p=NS). Conclusions: In this real-world study, almost one-third of RAEB pts treated with IV/SC HMAs discontinued before 4 cycles, with almost half of these pts discontinuing after only 1 cycle. Predictors of HMA discontinuation included older age and poor PS. Novel approaches are needed to improve persistence with HMA therapy, particularly among these higher-risk groups.[Table: see text]
Outpatient practice pattern and remote patient monitoring for axicabtagene ciloleucel CAR-T therapy in patients with aggressive lymphoma.
Authors: Bansal Radhika , Paludo Jonas , Holland Adam , Megan Spychalla , Alli McClanahan , Hathcock Matthew , Alkhateeb Hassan , Dingli David , Wang Yucai , Kenderian Saad , Kumar Shaji , Shah Mithun Vinod , Mustaqeem Siddiqui , Warsame Rahma M. , Villasboas Jose Caetano , Bennani Nabila Nora , Johnston Patrick B. , Ansell Stephen M. , Haddad Tufia C. , Lin Yi 
Published: June 2021

7554 Background: Chimeric antigen receptor T-cell therapy (CAR-T) are commonly administered inpatient due to concern for early onset cytokine release syndrome (CRS), especially with axicabtagene ciloleucel (axi-cel). We report Mayo Clinic Rochester experience for hospital-based outpatient (HBO) management of patients (pts) receiving axi-cel and identify opportunities for improvement. HBO is closely integrated with inpatient practice and includes the same specialty trained clinical team. It is the first point of contact 24/7 for pts and triage evaluations. Lymphodepletion chemotherapy and CAR-T infusion is given on HBO followed by daily monitoring till day 8 and thereafter, as clinically needed until admission criteria is met. Methods: We retrospectively analyzed database of pts who received axi-cel between 1/2018 and 1/2021. After 06/2020, remote patient monitoring (RPM) tools were implemented to collect patient-reported neurologic symptoms and vital signs via bluetooth-enabled devices 4 times daily through month 1. Adverse data trends are addressed by the HBO team. Results: Among 72 recipients, 89% received their cells outpatient; 8% remained outpatient for the entire month. CRS and neurotoxicity incidence were comparable to those reported from CIBMTR. Median time to first admission was 2 days (Table). Use of bridging therapy, increased CRP and LDH were associated with early admission (≤3 days). Median time to tocilizumab, steroid, oxygen support, vasopressor was 4 days after admission. Half of HBO visits required intervention such as blood transfusions, IV medications through the first month. Nine pts had enrolled in RPM to date; with 8 having evaluable data. With 4 scheduled entries/day, a median of 1 entry/day was skipped and 2 entries/day were answered incompletely. An average of 57 additional unscheduled entries were generated per pt. Among a median of 373 (range 91-522) readings per pt over the first month, 4% (2%-20%) of the readings generated alerts. An average of 4 alerts were seen within 48 hours prior to admission. Data including additional subjects will be presented at ASCO meeting. Conclusions: We report a feasible outpatient care model for management of axi-cel recipients with safe outcomes. Clinical characteristics associated with more aggressive disease are associated with likelihood of early admission. Early RPM experience suggest use of digital tools could improve monitoring compliance and may predict evolution to symptoms requiring escalation of care.[Table: see text]
Phase Ib trial of vactosertib in combination with pomalidomide in relapsed multiple myeloma: A corticosteroid-free approach by targeting TGF-β signaling pathway.
Authors: Malek Ehsan , Hwang Sunjin , Caimi Paolo Fabrizio , Metheny Leland L. , Tomlinson Benjamin Kent , Cooper Brenda W. , Boughan Kirsten M. , Otegbeye Folashade , Gallogly Molly , Driscoll James Joseph , De Lima Marcos J.G. 
Published: June 2021

8039 Background: Immunosuppression and osteoclast activation are two hallmarks of the bone marrow environment in Multiple Myeloma (MM). Corticosteroids have been used historically as part of anti-myeloma regimens due to their anti-plasma cell activity, however they potentially could suppress immune system and activate osteoclast further; therefore there is an unmet need for corticosteroid-free approaches in the era of emerging anti-cancer immunotherapy modalities. There is an abundance of Transforming Growth Factor-beta (TGF-β), a crucial cytokine in suppression of immune system as well as catabolic bone remodeling, in the MM microenvironment. Vactosertib (Vacto) is a small molecule TGF-β type I receptor inhibitor that has shown single agent activity against myeloma in the syngeneic 5T33MM murine mouse model. Here, we report the phase Ib trial of Vacto in combination with pomalidomide (Pom) without any corticosteroids (NCT03143985). Methods: pts with relapsed MM with at least two lines of therapies enrolled on a 3 + 3 dose escalation design and received Vacto, 60 mg/d, 120 mg/d, 100 mg BID and 200 mg BID in combination with standard dose of Pom (4mg) without corticosteroids. The primary objectives of the study was to assess safety and recommended phase 2 dose. Vacto tablets, taken once or twice daily for 5 days followed by 2 days without treatment, is administered in 28-day cycles, until progression of disease or intolerable toxicity. Results: 15 pts were enrolled on the study (Table). The most common non-hematologic adverse event (AE) was grade II fatigue and pain in one pt, one episode of grade III renal failure that took less than 7 days to get back to baseline on another patient, sinus bradycardia that reversed to sinus rythem and an Afib that was rate controlled with beta blocerks. No grade IV non-hematologic AE was observed. Three pts had grade III hematologic AE, no grade IV hematologic AE. Three out of 15 pts experienced progression of disease (PFS-6: 80%). Conclusions: The phase Ib data shows safety of this agent in combination with Pom. The efficacy assessment (PFS-6: 80%) is higher than the historical control (PFS-6: 20% in randomized Phase II study by Richardson et al. Blood. 2014) with Pom only (PFS-6: 20%) or Pom with corticosteroids (PFS-6: 40%). Further advancement of this agent in clinical trial pipelines for MM is planned. Clinical trial information: NCT03143985. [Table: see text]
Isatuximab plus carfilzomib and dexamethasone in relapsed multiple myeloma patients with high-risk cytogenetics: IKEMA subgroup analysis.
Authors: Spicka Ivan , Moreau Philippe , Martin Thomas G. , Facon Thierry , Martinez Gracia , Oriol Albert , Koh Youngil , Lim Andrew , Mikala Gabor , Rosiñol Laura , Yağci Münci , Cavo Michele , Risse Marie-Laure , Asset Gaëlle , Macé Sandrine , Van De Velde Helgi , Yong Kwee 
Published: June 2021

8042 Background: A prespecified interim efficacy analysis of the Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) + carfilzomib (K) and dexamethasone (d) (Isa-Kd) significantly improved progression-free survival (PFS) compared with Kd in patients (pts) with relapsed multiple myeloma (RMM) (HR 0.531; 99% CI, 0.318–0.889; P= 0.0007), with a clinically meaningful increase in minimal residual disease negativity (MRD-) (29.6% vs 13.0%) and complete response (CR) (39.7% vs 27.6%) rates, and a manageable safety profile. This subgroup analysis of IKEMA examined efficacy and safety in pts with high-risk cytogenetics [t(4;14), del(17p), and t(14;16)] and/or gain(1q21). Methods: Pts with 1–3 prior lines of therapy were randomized 3:2 to receive Isa-Kd (n = 179) or Kd (n = 123). High-risk cytogenetics was assessed by central laboratory analysis and defined as ≥1 of the following: del(17p): 50% cutoff; t(4;14) or t(14;16): 30% cutoff. Assessment of gain(1q21) was prespecified as ≥3 copies: 30% cutoff. Results: Of the randomized pts, 23.5% (Isa-Kd) and 25.2% (Kd) had ≥1 high-risk cytogenetic abnormality (CA); 26.3% (Isa-Kd) and 25.2% (Kd) had isolated gain(1q21). The addition of Isa to Kd improved PFS for pts with ≥1 high-risk CA and standard-risk pts (Table); pts with t(4;14) (HR 0.549; 95% CI, 0.232–1.301) had a more pronounced treatment effect than pts with del(17p) (HR 0.837; 95% CI, 0.281–2.496). A clear PFS benefit with Isa-Kd was also seen for pts with isolated gain(1q21) and gain(1q21) combined with other high-risk CA (Table). The trend toward improved CR, ≥very good partial response (VGPR), and MRD- rates with the addition of Isa was more pronounced in pts with gain(1q21) than in pts with high-risk CA alone. Grade ≥3 treatment-emergent adverse events (TEAEs) were more common with Isa-Kd vs Kd, but the incidence of serious and fatal TEAEs was similar with both arms for high-risk pts (Table). Conclusions: The addition of Isa to Kd improved PFS in pts with high-risk CA and disease response in pts with gain(1q21) isolated or combined with high-risk CA, with a manageable safety profile, consistent with the benefit observed in the overall IKEMA population. Isa-Kd is a potential new treatment option for the difficult-to-treat subgroup of pts with RMM and high-risk cytogenetics. Funding: Sanofi. Clinical trial information: NCT03275285. [Table: see text]
AFT-16: Phase II trial of neoadjuvant and adjuvant atezolizumab and chemoradiation (CRT) for stage III non-small cell lung cancer (NSCLC).
Authors: Ross Helen J. , Kozono David E. , Urbanic James John , Williams Terence Marques , DuFrane Carter , Bara Ilze , Schulze Katja , Brockman Jane Michelle , Wang Xiaofei F. , Gao Junheng , Vokes Everett E. , Stinchcombe Tom 
Published: June 2021

8513 Background: A minority of the approximately 40,000 US patients diagnosed annually with stage III NSCLC can be cured by concurrent CRT. Standard adjuvant immune checkpoint inhibitors (ICI) improve outcome for those patients who complete CRT with good performance status (PS) and without disease progression, but most patients diagnosed with unresectable stage III NSCLC will not meet the criteria for adjuvant ICI. AFT-16 investigated safety and efficacy of neoadjuvant and adjuvant atezolizumab as a strategy that may allow more patients to benefit from ICI. Methods: Eligible patients received 4 cycles (cy) of atezolizumab 1200 mg IV q 21 days followed by CRT with 60 Gy + weekly carboplatin and paclitaxel (CP), CP consolidation and adjuvant atezolizumab to complete 1 year of therapy (17 cy). The primary endpoint of disease control rate at 12 weeks (wks) has been reported. Secondary endpoints reported here include overall response rate, safety, and progression-free and overall survival (PFS, OS) measured from the start of induction therapy. Correlative science data and quality of life endpoints will be reported elsewhere. Results: 64 patients with unresectable stage III NSCLC, PS 0-1 and no active autoimmune disease or significant organ dysfunction were enrolled at 13 Alliance for Clinical Trials in Oncology sites from 11/2017 to 7/2019. 62 patients who received at least one dose of atezolizumab are included in this analysis. Median age was 63.9 years (range 38.1-86.5). Patients were 51.6% female, 77.4% white, 88.7% current & former smokers and 56.5% PS 0. All patients are off study treatment. Mean cycles of treatment received was 9 (1-17). 46 patients were alive at median follow up 24.1 mo (range 3 – 34.1 mo). PFS at 12 and 18 mo from start of induction atezolizumab was 66% (95%CI 55-79) and 57% (95%CI 45-71) respectively. Median PFS was 23.7 mo (95%CI 13.2-NE). OS at 18 mo was 84% (95%CI 75-94). Median OS is not yet estimable. Atezolizumab was well tolerated. One grade (gr) 4 Guillain-Barre syndrome and 1 each gr 3 pneumonia, pneumonitis and colitis were attributable to neoadjuvant atezolizumab. The remaining 9 severe adverse events were unrelated to ICI. Conclusions: Atezolizumab prior to and following CRT for stage III unresectable NSCLC was well tolerated with encouraging PFS and OS without unexpected safety signals. Analysis of correlative endpoints and quality of life are ongoing. Further study of induction atezolizumab is warranted in patients with unresectable stage III NSCLC. Support: https://acknowledgments.alliancefound.org ; Clinical trial information: NCT03102242.
Different exposure duration of adjuvant icotinib in stage II-IIIA non-small cell lung cancer patients with positive EGFR mutation (ICOMPARE study): A randomized, open-label phase 2 study.
Authors: Lyu Chao , Wang Rui , Li Shaolei , Yan Shi , Wang Yuzhao , Chen Jinfeng , Wang Liang , Liu Yinan , Guo Zhanlin , Wang Jia , Pei Yuquan , Yu Lei , Wu Nan , Chen Jun , Liu Yanheng , Li Shanqing , Han Bing , Ding Lieming , Mao Li , Yang Yue 
Published: June 2021

8521 Background: EGFR-TKI has been widely used in the treatment for advanced non-small cell lung cancer (NSCLC). Previous studies, such as the EVIDENCE study and the ADAURA study, have confirmed that patients with EGFR-mutated NSCLC could benefit from adjuvant EGFR-TKI treatment. However, the optimal duration time of adjuvant EGFR-TKIs has not been clearly defined. Methods: In this multicenter, randomized, phase 2 trial, eligible patients with II-IIIA stage EGFR mutation-positive NSCLC after R0 resection were randomized in 1:1 to receive adjuvant icotinib for 1 year (group A) or 2 years (group B). The primary endpoint was disease-free survival (DFS). Results: Between September 2013, and September 2018, 109 patients from 8 centers were enrolled in this study, among whom 55 were randomized to group A and 54 to B. As of August 24, 2020 (data cutoff), the median follow-up was 44.1 months (95%CI 37.1-49.9), 31 (56%) of 55 patients in the 1-year group and 25 (46%) of 54 patients in the 2-year group had DFS events. The median DFS was 48.92 months (95%CI 33.15, 70.11) in 2-year group and 32.89 month (95%CI 26.61, 44.78) in 1-year group, respectively. 2-year icotinib significantly prolonged DFS (HR 0.521, 95%CI 0.278, 0.976; p = 0.039). OS events were observed in 20 patients, the OS was not mature yet. Icotinib was re-given for 32 patients with disease recurrence or metastasis as first-line treatment, objective response occurred in 66.7% of 30 patients with measurable disease. Treatment-related adverse events were recorded in 41 of 55 (75%) patients in 1-year group and 36 of 54 (67%) patients in 2-year group, and grade 3 or 4 treatment-related adverse events occurred in 4 (7%) of 55 patients in the 1-year group versus 3 (6%) of 54 in the 2-year group, respectively. No treatment-related deaths or interstitial lung disease were reported. Conclusions: 2-year adjuvant treatment with icotinib resulted in a significantly lower risk of recurrence than 1-year adjuvant icotinib in patients with stage II-IIIA NSCLC positive EGFR mutations and was not associated with increased toxic effects. Clinical trial information: NCT01929200.
Modeling the cost-effectiveness of adjuvant osimertinib in resected EGFR-mutant non-small cell lung cancer patients.
Authors: Lemmon Christopher , Zabor Emily Craig , Pennell Nathan A. 
Published: June 2021

8527 Background: Adjuvant Osimertinib (Osi) was recently approved for resected EGFR-mutant non-small cell lung cancer (NSCLC) based on disease free survival (DFS) benefits from the ADAURA trial. Prior studies of adjuvant EGFR inhibitors yielding DFS benefits have lacked an overall survival (OS) benefit, leading to debate over early clinical implementation given the associated drug costs. This study aims to evaluate the cost-effectiveness (CE) of Osi in this setting. Methods: We constructed Markov models using post-resection health state transitions with digitized DFS data from the ADAURA trial to compare cost and quality-adjusted life years (QALYs) of the use of 3 years of adjuvant Osi versus placebo in the ADAURA patient population of stage IB to IIIA NSCLC patients over a 10-year time horizon. All patients entering the progressive disease (PD) state were assigned for re-treatment with Osi. Cost and utility values were derived from Medicare reimbursement data and literature (Table). A CE threshold of 3 times the GDP per capita was used. Deterministic sensitivity analyses were performed to assess the impact of a range of OS benefit, as the impact of adjuvant Osi on OS has not yet been reported. Results: The incremental cost-effectiveness ratio (ICER) for adjuvant Osi was $317,119.90 per QALY gained. Initial costs of Osi are higher in the first 3 years, but become lower than the placebo group in year 4 onward, with similar costs after year 7. Costs due to PD are higher in the placebo group through the first 6.5 years. Average pre-PD, post-PD, and total costs were $2,388, $379,047, and $502,937, respectively in the placebo group, compared to $505,775, $255,638, and $800,697, respectively in the Osi group. QALYs were higher in the Osi arm throughout. Sensitivity analysis using incremental OS gains reaches the CE threshold of $195,000 between 25-30% OS benefit of Osi over placebo. A 50% discount to the Osi annual cost yielded an ICER of $115,419. Conclusions: 3 years of adjuvant Osi is more cost-effective than placebo if one is willing to pay $317,119 more per QALY gained, with most costs accruing in the first 3 years as drug cost. This strategy became cost-effective with an OS benefit between 25-30% over placebo. Discount to Osi annual costs improves the ICER significantly. True cost-effectiveness of adjuvant Osi will require further study due to immaturity of ADAURA OS data and model limitations.[Table: see text]
Elderly patients with unresectable stage 3 NSCLC treated with definitive chemoradiation with or without durvalumab: Safety and outcomes.
Authors: Ryan Malcolm Isaiah , Weiss Jessica , Fares Aline Fusco , Tsao Ming Sound , Liu Geoffrey , Bradbury Penelope Ann , Leighl Natasha B. , Shepherd Frances A. , Sacher Adrian G. , Lau Sally C. M. 
Published: June 2021

8547 Background: Recently, it has been demonstrated that the addition of durvalumab after chemoradiation (CRT) in unresectable stage 3 non-small cell lung cancer (NSCLC) significantly improves overall survival (OS). The benefit of CRT in elderly patients is considered controversial given its increased toxicity. As such, CRT followed by durvalumab in elderly patients may be underutilized despite its demonstrated superiority. The practice pattern at our center is to offer curative treatment unless clearly contraindicated. We sought to investigate the outcomes of elderly patients treated with CRT +/- durvalumab at our center. Methods: We conducted a review of all stage 3 NSCLC patients treated with CRT between 2018 and 2020. Patients were analyzed based on age: < 70 years, ≥70 years. Endpoints evaluated were treatment patterns, toxicity, progression free survival (PFS) and overall survival (OS). Results: We identified 115 stage 3 patients: 44 patients ≥70 years (70-89) and 71 patients < 70 years (34-69). Patients were fit: ECOG 0-1 (98%/97%), mean Charlson comorbidity index (CCI) (1.1/0.9) in elderly vs young patients; p > 0.05. All other baseline characteristics including PD-L1 expression were similar. The chemotherapy regimens (platinum in combination with etoposide, paclitaxel or pemetrexed), dose intensity (97% vs 97%) and percentage of planned cycles received (91% vs 96%) were similar. There were 2 treatment related deaths from CRT among the younger cohort and none in the elderly patients. At the completion of CRT, 75% of elderly and 72% of young patients received durvalumab. Clinician/patient preference was the most common reason for not receiving consolidation durvalumab in older patients (55% vs 25%). The median time to starting durvalumab was 43 days in the elderly and 37 days in young patients (p = 0.19). Durvalumab was well tolerated in the elderly and incidence of grade ≥3 immune-related adverse events was 9% compared to 6% in young patients; p = 0.68. The durvalumab completion rates were 30% in elderly and 24% in young patients; p = 0.22. Median PFS was similar between elderly and young patients (17.9 vs 10.6 months respectively; p = 0.07), even after adjusting for the CCI (HR 0.60; p = 0.07). The 24- and OS rates are also similar (p = 0.93): 77% in elderly and 77% in young patients. Conclusions: Definitive CRT followed by durvalumab can be safely delivered in elderly patients ≥70 years with comparable outcomes. The non-significant trend towards better PFS in elderly patients suggests that only select fit patients are being referred for treatment. In conclusion, all patients should undergo comprehensive oncologic assessment to determine if curative intent treatment can be delivered to avoid undertreatment of elderly patients.