bluuebunny/crossref_metadata_2025_split huggingface dataset:
Access to definitive treatment and survival for intermediate-risk and high-risk prostate cancer at hospital systems serving health disparity populations.
Authors: Labban Muhieddine , Nguyen David-Dan , Briggs Logan , Cole Alexander P , Lipsitz Stuart R. , Iyer Hari S. , Rebbeck Timothy , Weissman Joel S. , Choueiri Toni K. , Trinh Quoc-Dien 
Published: June 2022

6555 Background: Socioeconomic and racial disparities in prostate cancer (PCa) can be attributed to patient-level and physician-level factors. However, there is growing interest in investigating the role of the facility of care in driving cancer disparities. Therefore, we sought to examine receipt of guideline-concordant definitive treatment, time to treatment initiation (TTI), and survival for men with PCa receiving care at hospital systems serving health disparity populations (HSDPs). Methods: We conducted a retrospective analysis of the National Cancer Database (2004-2016) among men with intermediate-risk or high-risk PCa eligible for definitive treatment. The primary outcomes were receipt of definitive treatment and TTI within 90 days of diagnosis. The secondary outcome was survival. We defined HSDPs as minority-serving hospitals – facilities in the highest decile of proportion of Non-Hispanic Black (NHB) or Hispanic cancer patients – and/or high-burden safety-net hospitals – facilities in the highest quartile of proportion of underinsured patients. We used mixed-effect models with facility-level random intercept to compare outcomes between HSDPs and non-HSDPs among the entire cohort and among men who received definitive treatment. We evaluated interactions between HSDP status and race for each of the outcomes. Results: The cohort included 821,931 men with intermediate-risk or high-risk PCa. We included 968 non-HSDPs (72.2%) and 373 HSDPs (27.8%) facilities. Treatment at HSDPs was associated with lower odds of receipt of definitive treatment (aOR 0.64; 95% CI 0.57-0.71; p < 0.001), lower odds of TTI within 90 days of diagnosis (aOR 0.74; 95% CI 0.68-0.79; p < 0.001), and worse survival (aHR 1.05; 95% CI 1.02-1.09; p = 0.003). However, no difference was found in survival among patients who received definitive treatment. NHB men at HSDPs had also worse outcomes than NHB men treated at non-HSDPs as well as NHW men treated at HSDPs (Table). Conclusions: Patients treated at HSDPs were less likely to receive timely definitive treatment and had worse survival. NHB men have worse outcomes than NHW at HSDPs. NHB men with PCa remain largely disadvantaged since they are more likely to be treated at hospitals with worse outcomes and have worse outcomes than other patients at those same institutions. [Table: see text]
Self-reported financial difficulties among patients with multiple myeloma and chronic lymphocytic leukemia: An Alliance for Clinical Trials in Oncology study.
Authors: Conti Rena M. , McCue Shaylene , Dockter Travis , Dusetzina Stacie , Rapkin Bruce D. , Weiss Elisa S. , Behrens Robert J. , Richardson Paul G. 
Published: June 2022

6602 Background: Treatment advances have greatly improved survival and quality of life among blood cancer patients, yet significant financial costs are a growing concern. Methods: We conducted an observational, prospective survey in 2019-2020 to estimate the self-reported prevalence of financial difficulty among multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients and identify sociodemographic correlates of financial difficulty. Patients with an MM or CLL diagnosis >/= 18 years of age were recruited from NCI NCORP sites of care. Financial difficulty was measured in a previously validated single question from the EORTC QLQ C30 and a composite measure of five questions from the EORTC QLQ C30. Results: 521 MM and CLL patients were registered to the study, 416 patients were administered all or part of the patient survey, for an overall response rate of 79.8%. 16.8% of respondents reported experiencing financial difficulty in response to the single item question and 58.6% reported experiencing financial difficulty in response to the composite measure. Respondents reporting financial difficulty to both measures had reported household incomes of less than $60,000, identified their highest education levels as a high school diploma or GED, had more than one medical comorbidity and used an expensive oral chemotherapeutic agent to treat their blood cancer. Conclusions: Blood cancer patients treated at NCI NCORP sites are experiencing financial difficulties. Results of this study aim to inform physician, site of care and policy efforts to improve access among cancer patients. Clinical trial information: NCT03870633. [Table: see text]
Assessing eligibility for non-intensive chemotherapy (IC) randomized clinical trials (RCT) in patients (pts) with newly diagnosed (ND) AML from the Connect Myeloid Disease Registry.
Authors: Erba Harry Paul , Pollyea Daniel Aaron , Sekeres Mikkael A. , Garcia-Manero Guillermo , Seiter Karen , DeGutis Irene , Kiselev Pavel , McBride Ali , Yu Edward , Roboz Gail J. 
Published: June 2022

7029 Background: Pts with AML in RCTs often do not reflect the population seen in clinical practice due to strict eligibility criteria. This study evaluated criteria from a recent RCT of non-IC against a broad cohort of real-world pts with AML from the Connect® Myeloid Disease Registry (NCT01688011). Methods: Pts were stratified into 3 groups based on the non-IC phase 3 VIALE-A trial eligibility criteria: 1) “eligible” pts who would have met all VIALE-A inclusion criteria; 2) “unfit” pts who would have been ineligible for VIALE-A due to ≥ 1 of the following: abnormal liver/kidney function, high ECOG, recent prior malignancy, comorbidities score ≥ 2 by ACE-27, hepatic grade ≥ 1, AIDS grade ≥ 1; 3) “fit” pts who would have been ineligible for VIALE-A because they would have qualified for IC (defined as: ≤ 74 y of age, low ECOG, no apparent cardiovascular/renal comorbidities, and did not meet any criteria in #2). Baseline characteristics were summarized by eligibility group. Overall survival (OS) by group was estimated using the Kaplan–Meier method. Induction regimens were categorized as IC (any regimens containing 7+3, MEC, CLAG, FLAG) or venetoclax (VEN)-based. Hazard ratios (HRs) for induction regimens among each group were estimated using Cox models adjusted for age, ELN risk, ECOG, frailty score, and comorbidity index. Results: Of 734 enrolled pts with AML (Dec 2021), most were male (61%) and white (84%); median age 71 y (range 55–97). Only 26% of pts (n = 192) were eligible for a non-IC RCT, 45% (n = 327) were ineligible due to unfitness, and 29% (n = 215) were ineligible due to overall fitness. The main reason for non-IC RCT ineligibility was high overall comorbidity grade (n = 265 [36%]). Fit pts intended to undergo transplant more often compared with unfit pts. Median OS for eligible, unfit, and fit pts were 14, 10, and 22 months, respectively. Among unfit pts, those receiving IC had significantly longer OS compared with pts receiving a VEN-based regimen (median OS 14 vs 6 months, respectively; HR: 0.51, 95% CI: 0.27–0.98, P = 0.042; Table). Eligible pts who received IC tended to have shorter median OS (13 months) vs pts who received VEN-based therapies (23 months; not sig.). Conclusions: The majority of pts with ND AML in the Registry would have been ineligible for a non-IC RCT due to being too fit or unfit. Pts ineligible for an RCT due to unfitness but who received IC maintained an OS benefit vs those receiving VEN-based therapies. This analysis suggests that non-IC RCTs may be excluding pts who appear unfit but can potentially tolerate IC and experience improved survival outcomes. Clinical trial information: NCT01688011. [Table: see text]
A phase Ib/II study of lisaftoclax (APG-2575), a novel BCL-2 inhibitor (BCL-2i), in patients (pts) with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (R/R CLL/SLL).
Authors: Li Jianyong , Zhou Keshu , Nian Weiqi , Cui Guohui , Wang Jishi , Zhang Xiaoping , Cen Hong , Li Fei , Yi Shuhua , Feng Ru , Xu Chongyuan , Qian Wenbin , Liu Lihong , Li Caixia , Zhao Xielan , Chen Zi , Qiao Junxiao , Zhang Hongli , Ahmad Mohammad , Zhai Yifan 
Published: June 2022

7543 Background: B-cell malignancies evade apoptosis by overexpressing BCL-2 proteins. Approved BCL-2i venetoclax requires a slow dose ramp-up to limit risk of tumor lysis syndrome (TLS) and has been associated with severe neutropenia. Investigational single-agent lisaftoclax is a novel, oral BCL-2i active against hematologic malignancies (HMs), with potentially synergistic antitumor effects when combined with other agents in B-cell malignancies. Methods: The aim of this multicenter open-label study was to evaluate dose-limiting toxicity (DLT), maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), efficacy, pharmacokinetics (PK), and pharmacodynamics of lisaftoclax in pts with R/R CLL/SLL (per 2008 iwCLL NCI-WG guidelines). Lisaftoclax was administered orally once daily at 3 dose cohorts (400, 600, or 800 mg) every 28 days, with 15 pts in each cohort. Results: As of the data cutoff date of January 25, 2022, 45 pts had been enrolled, with a median (range) age of 58 (38-80) years. DLT and MTD were not observed. The preliminary PK profile showed that exposures increased with lisaftoclax doses from 400 to 800 mg (average half-life: 4.2-6.6 hours). A total of 42 pts experienced any-grade treatment-related adverse events (AEs), including neutropenia (55.6%); anemia (42.2%); decreased leukocyte count (40%); thrombocytopenia (37.8%); lowered lymphocyte count (17.8%); hyperuricemia (31.1%); hypokalemia (24.4%); increased blood bilirubin (22.2%); hypertriglyceridemia (20%); diarrhea (20%); hyperphosphatemia, hypocalcemia, and decreased weight (15.6% each); increased AST (15.6%) and blood LDH (13.3%); pyrexia; and increased ALT and blood creatinine (11.1% each). A total of 28 (62.2%) pts experienced grade ≥ 3 AEs and 13 (28.9%) serious AEs. Of these, 25 (55.6% of total) and 9 (20%) were related to lisaftoclax, and 14 (31.1%) led to treatment discontinuation. One clinical TLS was reported. With a median (range) treatment of 7 (1-17) cycles and median (range) time to response of 1 (1-13) cycles, 1 of 41 evaluable pts with CLL experienced complete response (CR) and 27 with CLL/SLL achieved partial response (PR), for an objective response rate (ORR) of 68.29%. The RP2D of lisaftoclax as monotherapy was determined as 600 mg. Conclusions: BCL-2i lisaftoclax was well tolerated up to 800 mg/day. There were no significant new or unmanageable safety findings, and the ORR was 68.29%. Lisaftoclax may offer a treatment alternative for pts with R/R HMs, with a daily ramp-up schedule that may be more convenient and “user friendly.” Clinical trial information: NCT04494503.
A novel, immunotherapy-based approach for the treatment of relapsed/refractory multiple myeloma (RRMM): Updated phase 1b results for daratumumab in combination with teclistamab (a BCMA x CD3 bispecific antibody).
Authors: Rodríguez-Otero Paula , D'Souza Anita , Reece Donna Ellen , van de Donk Niels W.C.J. , Chari Ajai , Krishnan Amrita Y. , Martin Thomas G. , Mateos Maria-Victoria , Morillo Daniel , Hurd David Duane , Rosiñol Laura , Sureda Balari Anna , Wäsch Ralph , Vishwamitra Deeksha , Wang Lin Shun Xin , Prior Thomas , Vandenberk Lien , Smit Marie-Anne Damiette , Oriol Rocafiguera Albert , Dholaria Bhagirathbhai R. 
Published: June 2022

8032 Background: Teclistamab (tec; JNJ-64007957) is a BCMA × CD3 T-cell redirecting bispecific antibody under investigation in patients (pts) with RRMM. Daratumumab (dara) is a CD38 mAb with direct on-tumor and immunomodulatory actions. Initial clinical data from the phase 1b multicohort TRIMM-2 study support the combination of tec + dara for the treatment of RRMM, with tolerable safety, no overlapping toxicities, and promising efficacy. We present updated results with additional pts and longer follow-up. Methods: Eligible MM pts aged ≥18 y had received ≥3 prior lines of therapy (LOT; including a proteosome inhibitor [PI] and immunomodulatory drug [IMiD]) or were double-refractory to a PI and IMiD. Pts treated with anti-CD38 therapy ≤90 d prior were excluded. Pts received dara SC 1800 mg per approved schedule and tec SC 1.5–3 mg/kg QW or Q2W. Primary objectives were to identify the recommended phase 2 dose of tec for combination therapy and evaluate safety of the combination. Responses were assessed by IMWG criteria. AEs were graded per CTCAE v5.0; cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) were graded per ASTCT guidelines. Results: At data cutoff (Jan 13, 2022; safety population: N=46), median follow-up was 7.2 mo (range 0.1–16.6; median age 67 y [range 50–79]; 52% female). Pts received a median of 6 prior LOT (range 2–17; 74% triple-class exposed; 63% penta-drug exposed; 15% anti-BCMA exposed). 91% of pts had ≥1 AE (grade 3/4 78%), most commonly CRS (61%; all grade 1/2; median time to onset 2 d; median duration 2 d), neutropenia (54%; grade 3/4 50%), anemia (46%; grade 3/4 28%), thrombocytopenia (33%; grade 3/4 28%), and diarrhea (33%; grade 3/4 2%). Infections occurred in 29 pts (63%; grade 3/4 28%). One pt had grade 1 ICANS that fully resolved. Among 37 response-evaluable pts, ORR was 78% (29/37); 27 pts (73%) had very good partial response (VGPR) or better (Table). Median time to first response across dosing cohorts was 1.0 mo (range 0.9–2.8); median duration of response was not reached. Upregulation of CD38+/CD8+ T cells and proinflammatory cytokines was observed with tec + dara, supporting potential synergy of the combination in pts with prior anti-CD38 exposure. Updated results will be presented. Conclusions: Tec + dara provides a novel immunotherapy approach for the treatment of RRMM that may yield improved clinical efficacy in heavily pretreated pts. Clinical trial information: NCT04108195. [Table: see text]
Early intervention for high-risk and low-risk of progression for patients with smoldering multiple myeloma.
Authors: Sweeney Nathan W. , Cheung Christian S. , Molina Thomas H. , Ahlstrom Jennifer M. 
Published: June 2022

8058 Background: Previous studies have observed smoldering multiple myeloma (SMM) patients with a biomarker criteria of > 20% bone marrow plasma cells, > 2 g/dL M protein spike, and > 20 free light chain ratio, also known as 20/2/20, are at a higher risk of progressing to multiple myeloma (MM) than others. These findings have ignited interest in pursuing early intervention for these high-risk patients. However, we asked if early intervention would be beneficial for all SMM patients regardless of the progression risk level. Methods: We utilized real-world data from HealthTree Cure Hub for Multiple Myeloma to first, determine whether 20/2/20 resulted in a higher risk of progression and second, analyze whether early intervention delayed progression from SMM to MM. A 2-sample t-test was used to compare 20/2/20 to non-20/2/20 patients, as well as in the comparison between SMM patients who received early intervention with treatment to without early intervention. Results: We found that patients who met at least two of the criteria of 20/2/20 had a tendency to progress to MM 35% faster than patients who did not meet the criteria (n = 36, p-value < 0.10). While not significant, it’s still worth noting that there is a difference in the mean time to progression for these patients. Next, we found SMM patients who do not receive early intervention with treatment develop MM two times faster than those who do receive early intervention with treatment, regardless of progression risk level (n = 129, p-value < 0.001). Conclusions: Our results revealed that at least two of the biomarker criteria could aid in the identification of patients with a higher risk of progression. However, a casual approach of “sit and wait” for patients to develop 20/2/20 is not warranted since our findings revealed that all SMM patients benefited from treatment intervention regardless of the progression risk level.
Predictors of adjuvant chemotherapy refusal in lung cancer: A National Cancer Database Study.
Authors: Katel Anjan , Nelson Rebecca A. , Pathak Ranjan 
Published: June 2022

8521 Background: Adjuvant chemotherapy (AC) have been shown to improve overall survival in non-small cell lung cancer (NSCLC). Despite showing significant survival benefit across various age groups, patients are known to refuse AC. However, the factors associated with such a decision remain poorly understood in lung cancer. We therefore sought to investigate the factors associated with AC refusal in a nationally representative database in the United States (US). Methods: From 2004 to 2017, adults (≥20 years) with histologically confirmed non-small cell lung cancer (NSCLC) who underwent complete resection and were deemed to be chemotherapy eligible (node-positive or size ≥5 cm) were identified in the National Cancer Database (NCDB). Annual trends and factors associated with refusal of AC in chemotherapy-eligible NSCLC patients were evaluated using Joinpoint regression and multivariable logistic regression. Results: Among the 44,957 patients who met the inclusion criteria, 18,468 (3,678 (8.2%)) were noted to refuse chemotherapy in the NCDB. Patients refusing adjuvant chemotherapy were more likely to be elderly (OR 1.08, 95% CI, 1.07-1.08; P<.001), uninsured when compared with government insurance (OR 1.79, 95% CI, 1.38-2.33; P<.001), treated in the Western region of the when compared with patients in the Northeast (OR 1.47, 95% CI, 1.28-1.68; P<.001). They were also more likely to have a higher Charlson score versus patients with Charlson score of zero (OR 1.31, 95% CI, 1.18-1.46; P<.001), have squamous cell carcinoma versus adenocarcinoma (OR 1.20, 95% CI, 1.11-1.31; P<.001), undergo pneumonectomy versus lobectomy (OR 1.31, 95% CI, 1.16-1.47, P<.001), and have ≥2 weeks hospital length of stay versus < 2 weeks (OR 2.25, 95% CI, 1.93-2.63; P<.001). Conclusions: In our analysis, we identified several sociodemographic and clinicopathologic variables that were independently associated with chemotherapy refusal. We saw the number of patients refusing AC increased sharply during the study period. Our study shows that in addition to poor post-operative recovery, underlying sociodemographic factors might predict patients at risk for refusing adjuvant chemotherapy in lung cancer. Further understanding of these factors might help devise effective interventions to motivate patients to undergo potentially life-extending chemotherapy in lung cancer.
A phase I study of anlotinib with concurrent chemoradiotherapy for limited-stage small cell lung cancer.
Authors: Huang Dingzhi , Ren Kai , Wang Xinyue , Lin Li , Chen Jinliang , Wang Liuchun , Meng Zhaoting , Zhao Lujun 
Published: June 2022

8579 Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for limited-stage small-cell lung cancer (LS-SCLC). However, LS-SCLC remains an area of high unmet medical need. Anlotinib is an antiangiogenic multi-target tyrosine kinase inhibitor. In the phase II ALTER-1202 trial, anlotinib significantly improved clinical outcomes in advanced small-cell lung cancer. We report here a phase 1 trial of anlotinib with CCRT for LS-SCLC. Methods: This is a prospective, single-arm, phase I clinical trial using a 3+3 design. Patients aged between 18 and 75 with previously untreated LS-SCLC, PS 0-1 and adequate organ function are eligible. Patients received anlotinib (12mg, qd, d1-14, q3w) and chemotherapy (etoposide, 100 mg/m2, d1-3, q3w and cisplatin, 25 mg/m2, d1-3, q3w) for cycle 1, then anlotinib [dose escalation at 3 levels (DL1-3) 8mg, 10mg and 12mg, qd, d1-14, q3w], chemotherapy (etoposide, 50 mg/m2, d1-5, q4w and cisplatin, 25 mg/m2, d1-3, q4w) and thoracic radiotherapy (60-66 Gy in 30-33 daily 2-Gy fractions starting on day 1 of cycle 2) for cycles 2–3, then anlotinib (12mg, qd, d1-14, q3w) and chemotherapy (etoposide, 100 mg/m2, d1-3, q3w and cisplatin, 25 mg/m2, d1-3, q3w) for cycles 4-6. Cycles 5-6 were given as appropriate according to the patient's physical condition. Prophylactic cranial radiation was given according to the judgment of the investigator after CCRT. The purpose of this study is to determine the maximum tolerated dose (MTD) of anlotinib when combination with CCRT. Results: Twelve patients were enrolled from May 2020 to September 2021. No DLTs were observed in DL1 (3 patients) or DL2 (3 patients). At DL3 (6 patients), 1 patient had a DLT of grade 3 pulmonary embolism. Grade 3 adverse events were white blood cell count decreased, neutrophil count decreased, lymphocyte count decreased, hypertension, albumin decreased and pulmonary embolism. One patient had grade 3 pulmonary embolism and grade 4 neutrophil count decreased in DL3 at cycle 1. One patient had grade 2 radiation pneumonitis after cycle 5 and grade 1 radiation esophagitis at cycle 3 in DL3. One patient had grade 2 radiation esophagitis at cycle 3 in DL2. The MTD was not reached. Conclusions: Combined treatment with anlotinib and CCRT for limited-stage small cell lung cancer is well tolerated and further clinical investigation is warranted. Clinical trial information: NCT04882033.