bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of sex on outcomes in patients with hairy cell leukemia (HCL): An HCL Patient Data Registry (PDR) analysis.
Authors: Epperla Narendranath , Zhao Qiuhong , Anghelina Mirela , Neal Jasmine , Blachly James Stewart , Rogers Kerry Anne , Lozanski Gerard , Oakes Christopher , Bhat Seema , Banerji Versha , Zent Clive , Grever Michael R. , Andritsos Leslie Ann 
Published: June 2022

7577 Background: HCL is a rare indolent leukemia that is more common in men, with a 4:1 male predominance. To date, no studies have characterized the potential difference in outcomes of HCL between male and female patients. Hence, we sought to evaluate the outcomes of female HCL patients using the HCL-PDR. Methods: The HCL Foundation sponsored the development of HCL-PDR to characterize the clinical features and outcomes of this rare leukemia. HCL-PDR is an international multicenter PDR that includes patient, disease and treatment information abstracted from medical records. Adult patients enrolled in the HCL-PDR were included in the study. Female patients with HCL were the study population, with males as the comparator. The primary endpoint was the time to next treatment (TTNT) in females compared to males. Secondary endpoints included response rates (RR) and predictors of TTNT. Responses were categorized as: complete response (CR) including CR/CRu (CR unconfirmed)/HR (hematologic response), and partial response (PR), which included PR/PRu (PR unconfirmed)/pHR (partial HR). CRu was defined as no disease in bone marrow (BM) without available blood counts and HR as blood counts meeting criteria for HR, but no available BM. Cox proportional hazard models were used to estimate the hazard ratios for TTNT risk. Results: 357 patients were included: 265 males and 92 females. Table shows baseline characteristics stratified by sex. Among the patients who had disease status assessed after first treatment (n=224, males 169 and females 55), there was no significant difference in RR. However, females had significantly longer median TTNT (17.6 years) relative to males (8 years, HR 0.54, 95% CI 0.32-0.91, p=0.02) that remained significant after adjusting for other variables (RR and BRAF mutation) in multivariable analysis (HR 0.32, 95% CI 0.11-0.97, p=0.04). Factors predictive of longer TTNT include female sex and CR (HR.0.26, 95% CI 0.11-0.57, p=0.001). Conclusions: This is the first study to date reporting the clinical characteristics and outcomes in female HCL patients. The significantly longer TTNT in females compared to males may be related to factors such as underlying molecular features or hormonal influences. This finding needs to be explored further. [Table: see text]
Comparative effectiveness of teclistamab versus real-world treatments for patients with triple-class exposed (TCE), relapsed/refractory multiple myeloma (RRMM).
Authors: Krishnan Amrita Y. , Nooka Ajay K. , Chari Ajai , Garfall Alfred L. , Martin Thomas G. , Nair Sandhya , Lin Xiwu , Qi Keqin , Londhe Anil , Pei Lixia , Ammann Eric , Kobos Rachel , Smit Jennifer , Parekh Trilok V. , Slavcev Mary , Usmani Saad Zafar 
Published: June 2022

8036 Background: Teclistamab is a B-cell maturation antigen × CD3 bispecific antibody currently being evaluated in MajesTEC-1 (NCT04557098), an open-label, single-arm, phase 1/2 trial in patients with RRMM who had received ≥3 prior lines of therapy (LOT) and were TCE to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Given the absence of a control arm in MajesTEC-1, we assessed the comparative effectiveness of teclistamab versus treatment regimens using an external control arm from a real-world database. Methods: An external control arm for MajesTEC-1 was created from eligible patients in the nationwide de-identified electronic health record-derived Flatiron Health multiple myeloma cohort database who started a new line of therapy (physician’s choice) following triple-class exposure between January 2011 and August 2021, received ≥3 prior LOT, and satisfied key MajesTEC-1 eligibility criteria. Individual patient data from MajesTEC-1 included patients who received teclistamab (1.5 mg/kg weekly) at a clinical cutoff of Sep 7, 2021. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances in baseline covariates of prognostic significance: refractory status, progression on last LOT, cytogenetic risk, International Staging System stage, number of prior LOT, time since diagnosis, age, and hemoglobin. Outcomes of interest included progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS); these outcomes were analyzed as time-to-event data using IPTW adjusted Kaplan-Meier estimates and a weighted Cox proportional hazards model. Several sensitivity analyses were conducted. Results: After IPTW, baseline characteristics were comparable between the 2 cohorts. Patients treated with teclistamab had improved PFS (hazard ratio [HR] 0.43; 95% confidence interval [CI] 0.32–0.59; P< 0.0001), TTNT (HR 0.42; 95% CI 0.31–0.58; P< 0.0001), and OS (HR 0.73; 95% CI 0.48–1.09; P= 0.13) versus assessed real-world treatments. Results were similar for all sensitivity analyses. Conclusions: Teclistamab showed improved effectiveness for PFS, TTNT, and OS, compared with real-world treatments used in patients with TCE RRMM who received ≥3 prior LOT. These findings highlight the therapeutic potential of teclistamab in patients with RRMM who have limited treatment options.
Factors associated with dose adjustment for the bortezomib, lenalidomide, dexamethasone regimen among patients with newly diagnosed multiple myeloma.
Authors: Ran Tao , Medhekar Rohan , Fu Alex Z. , Patel Sharmila , Kaila Shuchita 
Published: June 2022

8039 Background: VRd (bortezomib/lenalidomide/dexamethasone) has become one of the established treatment regimens in the US for multiple myeloma (MM). Due to toxicities, dose adjustments are often required for VRd. This real-world study described the patient characteristics and factors associated with dose adjustment among MM patients treated with VRd as first line (1L) therapy. Methods: Adult MM patients treated with 1L VRd were selected from the Optum Clinformatics database (Nov 1, 2015-Sep 30, 2020). Patient characteristics were evaluated during a 6-month baseline period. Dose adjustments were defined based on lenalidomide (len) dose received during 1L. Receipt of > 15mg len was categorized as VRd regular, ≤15mg len as VRd lite, and initial len dose > 15mg reduced to ≤15 mg over treatment period as VRd reduced. Baseline factors associated with different VRd dose categories were studied using multinomial logistic regression. Results: Among the 1497 patients identified, the mean (SD) age was 69 (9.5) years (52% ≥70), 51% were male, 59% were White, 37% were frail, and 67% with Medicare. Baseline Charlson Comorbidity Index was 4.2, with hypertension (70%), hyperlipidemia (56%), renal impairment (26%), and CVD (25%) being the most prevalent comorbidities. Over half of the patients received an adjusted dose, VRd lite (33%) and VRd reduced (22%). Overall, for patients treated with 1L VRd, median follow-up was 16.2 months; median duration of 1L was 4.9 months (among those with confirmed end of therapy); and median TTNT was 14.5 months. Compared to VRd regular, use of VRd lite was over 6 times more likely to be associated with patients ≥75 years of age, about 2 times more likely to be associated with females, and about 40% less likely to be associated with commercial insurance vs. Medicare; VRd reduced was 1.3 times more likely to be associated with females, and 1.5 times more likely to be associated with frail patients (table). No differences were observed among different races. Conclusions: Over half of the MM patients treated with 1L VRd in the real-world were > 70 years of age and over one-third were frail. A large proportion of patients received a modified dose of VRd. Receipt of VRd lite dose was highly associated with older age (≥75 years), and receipt of VRd reduced dose was associated with frailty. These dose adjustments may potentially result in reduced efficacy of the VRd regimen in the real-world relative to controlled clinical trials, which needs to be assessed in future studies. [Table: see text]
Clinicopathological characteristics of high-risk multiple myeloma in Hispanic versus non-Hispanic patients in central California.
Authors: Hwang Andrew , Doornenbal Jason , Park Daniel , Bal Inderpreet , Bukari Mohammed SANI , Yan Yueqi , Abdulhaq Haifaa 
Published: June 2022

8056 Background: Roughly 37% of Multiple Myeloma (MM) patients in the U.S. are non-white minorities. Advanced stage at diagnosis and specific cytogenetic abnormalities are associated with high-risk disease and poor prognosis. Few studies evaluated these risk factors in ethnic minorities. To further investigate, we analyzed ethnic variations in characteristics and outcomes of high-risk MM patients who were treated at our institution in Fresno, CA (49.6% Hispanic population). Methods: Patients diagnosed with high-risk MM at Community Medical Centers from 1-1-2011 to 12-31-2020 were included. High risk was defined by Mayo Clinic mSMART 3.0 classification. Demographic and disease-relevant information were collected. Cytogenetics, R ISS stage, 1st line treatment (doublet vs triplet), and treatment response (IMWG response criteria) were evaluated. Hispanic and non Hispanic comparisons were made by Fisher’s exact test where appropriate. Progression Free Survival (PFS) and Overall Survival (OS) were evaluated by Kaplan-Meier estimates and compared via log-rank test. Univariate cox proportional hazard model for survival was used to examine the association of variables with mortality risk after 1st line therapy. Results: 147 MM patients were screened. 42 high risk patients were identified: 11 (26%) Hispanic, 31 (74%) non Hispanic (22 white, 8 African American, 1 East Indian). Median age at diagnosis was 65. 26 (61%) were females. 25 (59%) were R ISS stage 3. Hispanic vs non Hispanic median income was $46119 vs $65080 (p=0.035). 6 Hispanics had Medi-Cal insurance vs 2 non-Hispanics (54.6% vs 6.5%, p=0.003). More Hispanics had Lambda light chain disease (73% vs 26%; p=0.01). 13 non Hispanics had del 17p vs 0 Hispanics (p=0.009). 40/42 patients (95%) received triplet therapy. 4 Hispanics received ASCT vs 9 non Hispanics (40% vs 33.3%, p=0.716). Hispanics and non Hispanics did not have significantly different treatment responses per IMWG criteria (p=0.799). No significant difference in PFS was seen between Hispanics and non Hispanics (805 vs 793 days; p=0.089); OS was better in Hispanics (1062 days vs 453 days; p=0.008). Per univariate cox proportional Hazard model, female sex (HR 4.34) and age (HR 1.05) were associated with higher mortality while Hispanic ethnicity was associated with lower mortality (HR 0.19). Conclusions: Hispanic and non Hispanic high risk MM patients differed significantly in median income, insurance, and del 17p incidence. These did not translate to a difference in 1st line therapy or treatment response. OS in our study is higher in Hispanic high-risk MM patients compared to other ethnicities and warrants further investigation. [Table: see text]
PD-L1 score as a prognostic biomarker in Asian patients with early-stage, EGFR-mutated lung cancer.
Authors: Saw Stephanie , Lai Gillianne , Tan Aaron C. , Zhou Siqin , Ang Mei-Kim , Lim Wan-Teck , Kanesvaran Ravindran , Tan Wan Ling , Rajasekaran Tanujaa , Chan Johan , Teh Yi Lin , Ong Boon-Hean , Takano Angela M. , Tan Eng Huat , Tan Sze Huey , Tan Daniel Shao-Weng 
Published: June 2022

8527 Background: Adjuvant Atezolizumab was recently approved in stage II-IIIA non-small cell lung cancer (NSCLC) with PD-L1 ≥1%. However, disease-free survival (DFS) benefit was mainly driven by PD-L1 ≥50% and among EGFR-mutated subgroup, atezolizumab did not demonstrate DFS benefit when PD-L1 0% patients were included. We sought to determine the prognostic value of PD-L1 score in early-stage EGFR-mutated NSCLC. Methods: Consecutive patients with Stage IA-IIIA NSCLC diagnosed 1/1/2010 – 31/12/2019 who underwent curative surgery at National Cancer Centre Singapore with evaluable EGFR and PD-L1 status were included. Co-primary endpoints were 2-year DFS and 5-year overall survival (OS) by Kaplan-Meier method. Results: 455 patients were included (267 EGFR-mutant; 188 EGFR-wildtype). Median age at diagnosis was 65 years, 52.3% (238/455) were males and 62.9% (286/455) were never-smokers. Adenocarcinomas comprised 92.1% (419/455) and 92.5% (421/455) had R0 resection. Stage IA comprised 42.4% (193/455), Stage IB 23.1% (105/455), Stage II 15.8% (72/455) and Stage IIIA 18.7% (85/455). Among EGFR-mutant, 45.3% (121/267) were Ex19del and 41.9% (112/267) were L858R. PD-L1 ≥1% among EGFR-mutant and EGFR-wildtype was 55.8% (149/267) and 60.1% (113/188) respectively (p = 0.361). PDL1 ≥50% was significantly associated with higher stage at diagnosis among EGFR-mutant (p < 0.001) but not EGFR-wildtype (p = 0.319). At median follow up of 47 months, 178 patients had relapsed. Among EGFR-mutant, 2-year DFS comparing PD-L1 0% and PD-L1 ≥1% was 79.0% and 68.9% (p = 0.006) while 5-year OS was 87.6% and 70.6% (p = 0.006) respectively. 2-year DFS and 5-year OS by PD-L1 tertile (as shown in table) revealed that higher PD-L1 score was prognostically worse for both DFS and OS among EGFR-mutant. A similar trend was observed among EGFR-wildtype but did not reach statistical significance, apart from PD-L1 ≥50% which had significantly inferior DFS. Conclusions: Higher PD-L1 score was significantly associated with worse DFS and OS among early-stage EGFR-mutated NSCLC, possibly due to higher stage at diagnosis among PDL1 ≥50%. Our study highlights the poor prognosis of PDL1 ≥50% EGFR-mutated NSCLC in a pre-osimertinib era and underscores the importance of personalised risk-stratified adjuvant strategies. [Table: see text]
Neoadjuvant nivolumab in early-stage non–small cell lung cancer (NSCLC): Five-year outcomes.
Authors: Rosner Samuel , Reuss Joshua E. , Zahurak Marianna , Taube Janis M. , Broderick Stephen , Jones David Randolph , Chaft Jamie E. , Forde Patrick M. 
Published: June 2022

8537 Background: Neoadjuvant (neoadj) immune checkpoint blockade (ICB) with anti-PD-1 therapy has shown increasing promise for early stage NSCLC, with long-term clinical outcomes still maturing. Our group reported the first phase I/II trial of neoadj nivolumab (nivo) in resectable NSCLC, finding therapy to be safe and feasible. We now present final clinical results from this cohort, representing the longest follow up data for neoadj anti-PD-1 to date. Methods: Two doses of neoadj nivo (3 mg/kg) were given prior to resection in 21 patients (pts) with resectable NSCLC. 5-year (yr) follow-up data, including recurrence-free survival (RFS), overall survival (OS) and association with pathologic response were tabulated. Event time distributions were estimated with the Kaplan-Meier method. All p-values are two-sided with 0.05 significance level. Results: At a median follow up of 63 months, 3-, 4- and 5-yr survival rates were 85, 80, and 80% respectively. RFS rates at 3-, 4- and 5-yrs were 65, 60, and 60% respectively. As previously reported, major pathologic response (MPR: ≤10% viable tumor) was 45%, and pathologic complete response (pCR) rate was 10%. The hazard ratio (HR) for pathologic down-staging was in the direction of improved RFS, without meeting statistical significance (HR 0.36, 95% CI 0.07-1.75, p = 0.2). RFS HR estimates for MPR and an alternative pathologic cut-off of less than 50% residual tumor (RT), were 0.61, (95% CI 0.15-2.44, p = 0.48) and 0.36, (95% CI 0.09-1.51, p = 0.16) respectively. The direction of the effect of pre-treatment PD-L1 positivity (≥1%) was to improve RFS (HR 0.36, 95% CI 0.07-1.85, p = 0.22). At 5-yr follow up, 8 of 9 (89%) pts with MPR were alive and no cancer deaths have occurred. Amongst pts with MPR, 1/9 pts had a cancer recurrence in the mediastinum treated successfully with definitive chemoradiotherapy. Both pts with pCR are alive and without recurrence. Patterns of all recurrences in this cohort are summarized in table 1. No long-term immune-related adverse events have occurred other than one G3 dermatologic event. Conclusions: The 5-yr clinical outcomes for neoadj nivo in resectable NSCLC compare favorably to historical trends. MPR trended toward improved RFS, while definitive conclusions are limited by our cohort size and overall low recurrence rate. Thresholds of %RT beyond pCR and MPR in this setting should be explored in larger prospective studies. PD-L1 expression may play a role in predicting long-term response, but larger prospective studies are needed. Clinical trial information: NCT02259621. [Table: see text]
Racial disparities in receipt of curative surgery for early-stage non–small cell lung cancer in Florida.
Authors: Liu Qinran , Jacobs Kamaria T. , Lopes Gilberto , Brown Clyde P. , Pinheiro Paulo S. 
Published: June 2022

8539 Background: Lung cancer is the leading cause of cancer death in the United States. Receipt of curative-intent surgery for early-stage non–small cell lung cancer (NSCLC) is associated with disparities in race and socioeconomic status, which is subsequently related to the outcome of NSCLC. This study aimed to examine the racial disparity in receipt of curative-intent surgery among early-stage NSCLC in Florida. Methods: A total of 80,458 patients with early-stage NSCLC diagnosed from 2005 to 2017 were identified from the statewide cancer registry, Florida Cancer Data System (FCDS). Percentage of patients receiving curative-intent surgery was calculated for each race/ethnicity. FCDS data was linked to discharge data containing comorbidity information for each lung cancer patient. There was a 94% match between FCDS and discharge data. Multivariable logistic regression was used to determine the impact of race on receipt of curative-intent surgery for early-stage NSCLC. Results: Among 80,458 patients with early-stage NSCLC, 66,761 (83.0%) were White, 5,503 (6.8%) were Black and 6,981 (8.7%) were Hispanic. Of note, 69.5% Hispanic patients lived in South Florida. Asian patients (59.9%) had the highest proportion of curative surgery, followed by Hispanics (57.8%), Whites (52.9%) and Blacks (42.6%). In the multivariable model, patients with Charlson Comorbidity Index (CCI)≥3 had 34% lower odds of having curative surgery (OR, 0.66; 95% CI, 0.62 to 0.7) compared to patients who did not have any comorbidity (CCI=0). Highest poverty levels had 27% lower odds of receiving curative-intent surgery compared to lowest (OR: 0.73; 95% CI: 0.68 to 0.78). After adjusting for sociodemographic factors (i.e., age, sex, race, insurance, region) and clinical factors (i.e., histology, AJCC stage, CCI, smoking status), Blacks had 27% lower odds of receiving curative-intent surgery (OR, 0.73; 95% CI, 0.68 to 0.79), whereas Hispanics had 22% (OR, 1.22; 95% CI, 1.14 to 1.30) and Asians had 19% (OR, 1.19; 95% CI, 0.98 to 1.46) higher odds than Whites. In the stratified analysis by regions, Blacks had lower odds of receiving curative-intent surgery than Whites in all regions across Florida while Hispanics had higher odds of receiving surgery than Whites only in South Florida (OR, 1.29; 95% CI, 1.18 to 1.41). Conclusions: There are persistent racial disparities in receipt of curative-intent surgery for early-stage NSCLC in Florida. Specifically, Blacks are receiving less curative-intent surgery, despite adjustments for comorbidities, socio-economic status, and insurance. Ethno-regional differences within different regions of Florida are evident with Hispanics surpassing all other races in receipt of curative treatment in heavily Hispanic South Florida.
Dynamic monitoring circulating tumor DNA in plasma samples by PEAC technology for patients with early-stage non–small cell lung cancer after surgery.
Authors: Li Ning , Wang Bao-Xiao , Ou Wei , Wang Tao , Pu Yue , Zhu Teng-Fei , Hu Xin-Xin , Wang Siyu 
Published: June 2022

8547 Background: Local recurrence or distant metastasis after surgery is not rare for early-stage Non-Small Cell Lung Cancer (NSCLC) patients. Present clinicopathological parameters, such as TNM stages and pathological subtype, are limited effective, as Positive Predictive Value (PPV) is low while Negative Predictive Value (NPV) is high. In recent years, circulating tumor DNA (ctDNA) has emerged as a noninvasive method for early diagnosis, prognostic stratification, disease surveillance, and treatment response evaluation. We assessed whether circulating tumor DNA (ctDNA) detected by PEAC technology could be a biomarker for minimal residual disease (MRD) and prediction of postoperative relapse in early-stage NSCLC. Methods: We enrolled 132 NSCLC patients with EGFR, KRAS, NRAS, BRAF and PIK3CA mutations, and obtained plasma samples at five perioperative time points (before surgery, 3-7 days, 6-months, 12-months and 18-months after surgery). Using PEAC technology, somatic mutations in plasma samples were identified and utilized for ctDNA-based MRD analysis. Clinical follow-ups were collected. Results: Our data showed that 32.0% (8 of 25) of patients with positive preoperative ctDNA experienced postoperative relapse, compared with 7.2% (6 of 83) in ctDNA negative patients, demonstrating that preoperative ctDNA status is an effective prognosis factor for NSCLC. In time point of 3-7 days after surgery, plasma samples were obtained from 47 patients, of which 33.3% (2 of 6) with positive ctDNA experienced postoperative relapse, while only 4.9% (2 of 41) in ctDNA negative patients. The result suggests that ctDNA positive in plasma samples of 3-7 days after surgery might be a strong biomarker for MRD detection and relapse prediction. For ctDNA surveillance, plasma samples from 6-months, 12-months and 18-months after surgery were collected and detected. At any one of the three tests ctDNA is positive, 20.0% (8 of 40) patients experienced clinical relapse, while 5.1% (3 of 59) patients with ctDNA negative status at all times relapse. A total of 14 recurrence events had occurred, ctDNA positivity precedes radiological recurrence by a median of 150.5 days (90.5 – 182, P = 0.006). Conclusions: Perioperative ctDNA analysis using PEAC technology is effective in early detection of MRD and relapse prediction, and hence could benefit NSCLC patient management in clinical settings. Clinical trial information: NCT03465241.