bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association of agent orange (AO) exposure with monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) progression: A population-based study.
Authors: Liu Lawrence , Wang Mei , Schroeder Mark A. , Thomas Theodore Seth , Kumar Akhil , Vargo Kristin , Gao Feng , Sanfilippo Kristen Marie , Chang Su-Hsin 
Published: June 2022

8050 Background: With limited evidence from a single center study [n=211 (11 with AO exposure)] reporting AO exposure as a risk factor for transformation, whether or not AO exposure increases the rate of transformation from MGUS to MM is unclear. Thus, we aimed to conduct a nation-wide study to determine the association between AO exposure and the risk of MGUS to MM progression. Methods: A retrospective, matched cohort study using data from the U.S. Veterans Health Administration system was conducted. Based on a power calculation, a random sample of MGUS patients with AO exposure was selected and 1:1 matched to those with MGUS without AO exposure (matching factors: age at MGUS diagnosis, race, body mass index categories). Data abstraction confirmed MGUS and MM diagnoses. In addition, information on date of diagnosis, MGUS subtype, and monoclonal protein (M-protein) values was performed. Patients were considered to have MGUS if they had M-protein detected on serum protein electrophoresis (SPEP) with immunofixation confirmation. The association of AO exposure with progression from MGUS to MM was examined using a multivariable Fine-Gray subdistribution hazard model with death as the competing event. The covariates included M-protein at MGUS diagnosis (>1.5, ≤1.5 g/dL [reference]), MGUS subtype (Immunoglobulin A, light chain, and Immunoglobulin G [reference]), and Charlson comorbidity score at MGUS diagnosis. A sensitivity analysis was conducted using inverse probability treatment weighted survival analysis to evaluate the robustness of the conclusion. Results: After excluding individuals with no confirmed MGUS or M MGUS subtype, a total of 563 MGUS patients with AO exposure and 563 matched controls were included. No statistically significant difference was observed in the progression of MGUS to MM between the AO exposed group and control group (adjusted hazard ratio (aHR) 0.78, 95% confidence interval (CI) 0.53 to 1.17). The sensitivity analysis demonstrated consistent results. Conclusions: Our carefully designed study does not show an association between AO exposure and progression of MGUS to MM in a national cohort of Veterans. [Table: see text]
Outcomes for transplant-eligible, newly diagnosed Black patients (Pts) with multiple myeloma (MM): The Levine Cancer Institute (LCI) experience.
Authors: Paul Barry , Atrash Shebli , Robinson Myra M. , Jagosky Megan , Bhutani Manisha , Varga Cindy , Pineda-Roman Mauricio , Friend Reed N. , Foureau David , Cassetta Kristen , Usmani Saad Zafar , Voorhees Peter M. 
Published: June 2022

8053 Background: Studies have revealed disparities for Black (B) pts with MM, including more advanced disease at presentation, delayed therapy with novel agents such as immunomodulatory drugs (IMIDs) and proteasome inhibitors (PIs), reduced access to autologous stem cell transplant (ASCT), and under-representation in clinical trials. However, B pts tend to be younger at diagnosis and less likely to harbor high risk disease biology, suggesting outcomes could be better relative to their White (W) counterparts. To better understand outcomes by race in the setting of more optimal treatment access, we pursued a retrospective analysis of pts treated at LCI undergoing ASCT as part of first line therapy. Methods: 255 pts (181 W pts, 74 B pts) transplanted between 3/2014 – 12/2018 were included. Analysis was restricted to pts with MM who underwent a single ASCT as part of first line therapy. Pts with < 1 year of follow-up and no overall survival (OS) events were excluded. Proportions were compared between groups with Fisher’s exact tests; OS and progression free survival (PFS) were evaluated with Kaplan Meier methods and compared between groups with log-rank tests. Results: Median follow-up for B and W pts was 5.0 yrs (0.9 – 7.8 yrs) and 4.1 yrs (0.5 – 8.0 yrs). At initial presentation, median age was 59 yrs (24 – 76 yrs) and 61 yrs (35 – 78 yrs, P= 0.038), anemia was present in 81.3% and 64.6% ( P= 0.020), renal impairment in 41.3% and 33.1% ( P= 0.335), and high-risk cytogenetics [gain 1q21, t(4;14), t(14;16) or del(17p)] in 25.4% and 35.9% ( P= 0.162) of B and W pts, respectively. Median time from diagnosis to ASCT was 0.6 yrs (0.3 – 2.4 yrs) and 0.5 yrs (0.3 – 2.0 yrs) for B and W pts. 35.2% of all B pts and 43.9% of all W pts treated at LCI during the study period underwent ASCT (48.3% and 64.4% of pts ≤70 yrs of age, P= 0.002), while 63.5% and 80.1% received PI/IMID-based induction therapy ( P= 0.009) and 90.5% and 93.4% received maintenance therapy post-ASCT ( P= 0.438), respectively. Although ≥very good partial responses were achieved in fewer B pts than W pts after induction (65.8% and 80.7%,( P= 0.014), there was no difference after ASCT (95.8% and 93.9%, P= 0.759). Median PFS was 5.9 yrs (95% CI 3.4 – 6.6) and 3.6 yrs (95% CI 3.0 – 4.5) for B and W pts ( P= 0.039). Median OS trended in favor of B pts ( P= 0.163) with 5-year OS of 83.0% (95% CI 71.2% - 90.3%) and 74.2% (95% CI 65.8% - 80.9%), respectively. Conclusions: Despite disparities in optimal induction therapy, Black pts with MM who underwent frontline ASCT enjoyed better PFS relative to W pts. Optimizing access to PI/IMID-based induction therapy and ASCT will be necessary to further improve OS.
Prognostic impact of t(11;14) on PFS1 among patients with myeloma receiving triplet induction therapy.
Authors: Pirmohammed Shama , Joseph Nisha , Hofmeister Craig C. , Heffner Leonard T. , Gupta Vikas Anand , Boise Lawrence , Dhodapkar Madhav V. , Lonial Sagar , Nooka Ajay K. , Kaufman Jonathan L. 
Published: June 2022

8064 Background: Presence of t(11;14) on plasma cells by FISH or metaphase cytogenetics is considered a standard-risk prognostic factor per IMWG risk-stratification. However, recent studies suggest inferior PFS and OS observed among t(11;14) patients relative to the standard-risk myeloma patients. In the context of the ongoing trials of BCL-2 inhibitors (venetoclax) among t(11;14) relapse/refractory myeloma patients yielding response rates closer to 90%, we review the prognostic impact of t(11;14) on PFS. These results may have implications for earlier incorporation of BCL-2 inhibitors among t(11;14) myeloma patients. Methods: Among the 1000 consecutive newly diagnosed myeloma patients uniformly treated with RVD induction therapy from January 2008 until August 2016, we have information on FISH probes for t(11;14) tested for 869 patients [121 - t(11;14) and 748 – no t(11;14)]. First, we explore the frequency of IMWG defined concomitant high-risk cytogenetic characteristics [del 17p, t(4;14), t (14;16)]. Next, we create a synthetic control cohort that received maintenance, and excluded patients exhibiting high-risk features to evaluate the relative prognostication conferred by presence of t(11;14). Median follow up was 91 months. Demographic and outcomes data were collected from IRB approved myeloma database and responses were evaluated per IMWG Uniform Response Criteria. Results: Median age is 61.2 years (range 16.3-79.83). 34% of the patients are above the age of 65. Men (14.1% vs 11.7%, p = NS) and blacks had higher rates of t(11;14) (16.1% vs 11.1%, p = 0.028). 17 (14%) had concomitant high-risk features – 4 (3.3%) had t(4;14), 3 (2.5%) had t(14;16) and 11 (9.1%) had del17p. Interestingly, the rates of amplification of 1q (26.1% vs 14.9%, p = 0.002), and del13 (34.7% vs 24.4%, p = 0.015) were higher among t(11;14) patients. Compared to the synthetic cohort, the post-induction and post-transplant responses were lower for t(11;14) patients as summarized in table 1. ≥VGPR for t(11;14) vs no t(11;14) post-induction were 48.2% vs 71.5% p < 0.001 and post-transplant were 83.1% vs 92.8% p = 0.001, respectively. The median progression-free survival for the t(11;14) and non-t(11;14) groups were 61.4 months (95% confidence interval (CI), 49.13-73.67) and 82.56 months (95% CI, 70.47-94.65) months, respectively (p = 0.002). Conclusions: Even with the use of modern day induction regimens and transplant, patients with t(11;14) seem to have inferior response rates compared to the other standard-risk myelomas. The lower rates of ≥VGPR post-induction and the shorter median PFS suggests BCL-2 inhibitors such as venetoclax may be incorporated earlier in myeloma treatments to improve the outcomes of t(11;14) patients on par with the other standard-risk myeloma patients.
Immune cell differences between patients in different stages of monoclonal plasma cell disorders.
Authors: Ho Christine , Wallace Paul K. , Attwood Kristopher , Parker Sarah , Mohammadpour Hemn , Herr Megan , Chen George , Tario Joseph , McCarthy Philip L. , Hillengass Jens 
Published: June 2022

8065 Background: Multiple myeloma (MM) is an incurable plasma cell malignancy. Precursor conditions include monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma (SMM). Immune surveillance is paramount for keeping the malignancy in check, whereas a dysfunctional immune system is suspected to promote disease progression. Methods: We performed flow cytometric immune panel analyses including T-cell, B-cell, natural killer (NK) cell and dendritic cell (DC) subsets in MGUS, SMM, and MM patients between 2018-2021. Immune panels were analyzed on fresh peripheral blood samples drawn at diagnosis. The patient population were MGUS (n=28), SMM (n=19) and MM (n=94). Samples from MGUS and SMM patients were combined into a single group (asymptomatic) and were compared to MM patients (symptomatic). Lymphocytes were identified by CD45+ expression resolving against side-scattered light on a bivariate plot. B cell and NK cell antigen expression profiles were assessed from this lymphocyte population. T cell subsets were further determined by CD3+. The percent gated for each marker was summarized by cohort using the appropriate descriptive statistics and compared using the Mann-Whitney U exact test. Analyses were performed in SAS v9.4 (Cary, NC) using a two-sided α=0.05. Results: Compared to MGUS/SMM patients, MM patients had a significant lower proportion of naive B cells, NK cells, and cytolytic NK cells, and a significant higher proportion of cytolytic T cells at diagnosis (Table). Consistent with prior studies, we demonstrated an increase in exhaustion markers. There was a trend toward a higher population of CD8+ exhausted T cells in MM patients compared to MGUS/SMM patients. Since the follow up for this study was short, survival data is not mature. Conclusions: This study demonstrates the immune imbalance that occurs between myeloma precursor conditions and MM. There is a shift in certain cell subsets in the immune microenvironment that alters tumor immunosurveillance and tumor cell killing favoring disease progression. In data not shown, we are currently analyzing the bone marrow microenvironment and its relation to disease progression. Follow up studies could assess if therapeutic intervention could reverse the imbalance, restore homeostatic equilibrium with the goal of controlling disease long-term. [Table: see text]
Primary analysis from the phase 2 study of continuous talazoparib (TALA) plus intermittent low-dose temozolomide (TMZ) in patients with relapsed or refractory extensive-stage small cell lung cancer (ES-SCLC).
Authors: Goldman Jonathan W. , Cummings Amy Lauren , Mendenhall Melody A. , Velez Maria A , Babu Sunil , Johnson Tirrell T. , Alcantar Juan M. , Dakhil Shaker R. , Kanamori David E. , Lawler William E. , Anand Sidharth , Chauv James , Garon Edward B. , Slamon Dennis J. 
Published: June 2022

8517 Background: TALA exhibits cytotoxic effects by inhibiting poly (ADP-ribose) polymerase (PARP) proteins 1 and 2 in addition to “trapping” PARP on DNA. TMZ has been shown to increase antitumor response when combined with TALA in SCLC models (Wainberg AACR 2016). TALA plus TMZ as second-line therapy for ES-SCLC may improve disease-related outcomes. Methods: This is a phase 2, open-label, single-arm study of the safety and efficacy of TALA plus TMZ in patients with ES-SCLC, relapsed or refractory to a first-line platinum-based regimen. Participants receive TALA 0.75 mg (or 0.5 mg if creatinine clearance < 60 mL/min) po daily on 28-day cycles with TMZ 37.5 mg/m2 po on days 1-5. The primary endpoint is objective response rate (ORR) based on RECIST 1.1 criteria, versus a historical control of 15% ORR in second-line topotecan, with the null hypothesis rejected for 8 or more confirmed responses among 28 evaluable subjects (29% ORR). Secondary endpoints include progression-free survival, overall survival, duration of response, and time to response. Exploratory endpoints include biomarker studies such as status of DNA damage response genes (DDR) and patient reported outcomes. A Simon two-stage design was utilized to reach a total accrual of 28 evaluable patients. Results: Thirty-one subjects were enrolled, of which 3 were non-evaluable due to ineligibility (1) or early withdrawal of consent prior to first disease assessment (2). Eleven of 28 evaluable subjects (39.3%) achieved a confirmed partial response. The ORR was similar among platinum-refractory (3/6), -resistant (4/9), and -sensitive subgroups (4/13). The median time to response was 1.8 months (m), duration of response 5.8 m, progression free survival 4.5 m, and overall survival 11.9 m. Adverse events (AEs) were manageable, with grade ≥ 3 AEs being thrombocytopenia (61.3%), anemia (54.8%), neutropenia (41.9%), and atypical pneumonia (3.2%), which responded well to dose-hold or dose-reduction and transfusion or growth factor support as needed. Cell free DNA and tissue analysis demonstrated no germline DDR mutations among the trial subjects, but somatic DDR mutations at baseline and acquired during treatment were common. Three subjects remain on study treatment. Conclusions: The study exceeded its target response rate. This is the second trial to demonstrate a benefit of PARP inhibition with low-dose TMZ in SCLC (see Farago Cancer Discovery 2019). A phase 3 study is appropriate to confirm the benefit of this approach compared to currently approved options. Clinical trial information: NCT03672773.
Adjuvant icotinib versus observation in patients with completely resected, EGFR-mutated, stage IB non–small cell lung cancer (GASTO1003, CORIN): A randomized phase II trial.
Authors: Li Ning , Wang Bao-Xiao , Ou Wei , Shi Hena , Ji Dong , Yan Yan , Wang Shu-Quan , Chang Wu-Guang , Zhu Teng-Fei , Wang Si-Yu 
Published: June 2022

8519 Background: The role of adjuvant therapy in patients with completely resected stage IB non-small-cell lung cancer (NSCLC) remains to be determined. Icotinib is standard-of-care therapy for patients with advanced NSCLC harboring epidermal growth factor receptor (EGFR) mutation. This phase II study investigated whether adjuvant therapy with icotinib improves the clinical outcome compared with observation in patients with EGFR mutation-positive resected stage IB NSCLC. Methods: This phase II, open-label, randomized study (GASTO1003, CORIN) was conducted at Sun Yat-sen University Cancer Center. From May 2013 to December 2020, patients with completely resected, EGFR mutation-positive, stage IB (7th TNM staging for NSCLC) NSCLC without adjuvant chemotherapy according to physician and patient choices were enrolled. The patients were assigned in a 1:1 ratio to receive adjuvant therapy with icotinib (125mg, three times daily) for 12 months or to undergo observation. Therapy continued until disease progression or intolerable toxicity. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and toxicity. Survival endpoints were assessed in the intention-to-treat population. Results: Three patients withdrew consent and were excluded. A total of 128 patients were enrolled and randomized, with 63 patients in the icotinib group and 65 patients in the observation group. Baseline characteristics were well balanced between the groups. The median duration of follow-up was 34.9 months. A total of 13 recurrence events occurred, including 2 in the icotinib arm and 11 in the observation arm. DFS was significantly longer among those in the icotinib arm than among those in the observation arm (hazard ratio: 0.20, 95% confidence interval, 0.04-0.89; P = 0.018). The 3-year DFS for the icotinib and observation arms were 95.3% and 86.7%, respectively. The OS data were immature with 3 deaths in the observation arm. The safety profile was consistent with the known safety profile of icotinib. Icotinib was well tolerated with no unexpected adverse events. No treatment-related death occurred. Conclusions: Adjuvant icotinib shows prolonged DFS and acceptable toxicity in patients with completely resected EGFR-mutated stage IB NSCLC. Ajuvant icotinib provides a treatment option for these patients. Clinical trial information: NCT02264210.
Patients' preferences for adjuvant osimertinib in non–small cell lung cancer (NSCLC) after complete surgical resection: What makes it worth it to patients? (PATT)—The Roswell Park (RP) Comprehensive Cancer Center experience.
Authors: Mier-Hicks Angel , Attwood Kristopher , Catalfamo Kayla , Jain Prantesh , Chen Hongbin , Yau Edwin , Early Amy P. , Dy Grace K. 
Published: June 2022

8520 Background: There are clinical controversies surrounding the US FDA approval of Osimertinib in December 2020 as adjuvant therapy, based on disease-free survival (DFS) improvement in patients (pts) with surgically resected stage IB-IIIA EGFRm NSCLC. We initiated a survey study to investigate our hypothesis that DFS benefit alone even without significant OS maybe deemed a valuable endpoint to pts after considering trade-offs. Methods: Participants were recruited from pts seen at the RP Thoracic Clinic from 01/21 to 12/21. Eligible pts who were being evaluated for adjuvant systemic therapy following surgical resection were given a self-administered survey based on the validated questionnaire by Blinman et al, which was modified to provide explanation of the differences between OS and DFS and the ADAURA trial results. Survey responses were collected in an online repository. Associations between survey responses and demographics were assessed using Fisher’s exact test. Changes in preference responses were assessed using McNemar’s test. Results: A total of 524 pts with NSCLC were screened, of which 101 pts were eligible to receive the survey. 51 pts (50%) responded to the survey. Median age of respondents was 69yrs (37-83), majority were female (69%, n = 35,), married (61%, n = 31), retired ( 63%, n = 32), had at least some college or higher education level(54%, n = 28), with history of smoking (84%, n = 43) and with stage IIIA (43%, n = 22) adenocarcinoma (80%, n = 41). To evaluate toxicity-related tradeoffs (Q1), a ≥12 mo. improvement in OS benefit was needed for 66% of pts to consider adjuvant Osi. However, an increase of ≥ 6 mo. of DFS was enough for 66% of pts to justify taking a daily medication (Q2). One mo. increase in DFS or OS was not enough for 60% and 78% of pts respectively to justify taking the medication. A threshold 1% increase in 5-year OS was sufficient to persuade patients to take Osi for three years, even with respect to toxicity side effects (p = 0.023). (Q3). Finally, in the hypothetical cost-based scenario (Q4), there was no indication that pts were willing to pay more for each incremental increase in OS. There appears to be some association between employment status (p =.033) or educational degree (p =.049) for tolerance of side effects if there is at least 1 additional year of DFS or OS. Conclusions: We observed that the value patients ascribe to adjuvant Osimertinib is influenced by factors besides efficacy. Knowing pts' preferences for cancer treatments can better inform regulatory bodies in formulating cost-sharing structure for cancer therapies. Our study highlights the importance of shared decision making based on individual pts' preferences.
The Lung ART adjuvant radiotherapy phase 3 randomized trial: Impact of quality of resection in stage IIIAN2 patients.
Authors: Thomas Pascal Alexandre , Edwards John G. , Rami-Porta Ramón , Van Schil Paul , Mercier Olaf , Le Rochais Jean Philippe , Falcoz Pierre-Emmanuel , Meunier Jean-Pierre , Gkika Eleni , Kheira Hireche , Riesterer Oliver , Ghigna Maria Rosa , Bardet Aurelie , Le Pechoux Cecile ,   On behalf of LungART investigators (IFCT 0503, UK Lung ART Group, SAKK)
Published: June 2022

8522 Background: Lung ART is an international phase 3 trial whose main objective was to evaluate the impact of post-operative conformal radiotherapy (PORT) on disease-free survival (DFS) in patients with completely resected pathologically proven N2 non-small cell lung cancer (NSCLC), with or without neo- or adjuvant chemotherapy. Previously communicated results showed no impact of PORT on DFS. However, as quality of surgical resection and extent of lymph node dissection were expected to be critically important in the interpretation of results, surgical and pathological reports were centrally reviewed by a surgical committee. Methods: A surgical advisory committee composed of 4 expert thoracic surgeons reviewed anonymized surgical and pathological reports of all included patients. Pre-defined classification rules were defined using published guidelines from the International Association for the Study of Lung Cancer and the European Society of Thoracic Surgeons. Tumor resection was defined as complete (no residual tumor and adequate lymph node assessment), uncertain (highest mediastinal nodal station involved, incomplete nodal exploration, involved N2 removed in fragments) or incomplete (presence of residual tumor). Nodal exploration was classified as sampling, selective dissection or extensive dissection. Results: 501 patients were included in the Lung ART trial. Before surgical committee review intervention, all patients except 2 had complete resection. 496 patients’ reports were analyzed by the surgical advisory committee. The basic characteristics are specified in the following table: Conclusions: Monitoring of the quality of nodal exploration and of resection should be implemented in randomized studies evaluating peri-operative strategies in NSCLC in order to provide reliable and generalizable results. Clinical trial information: NCT00410683. [Table: see text]