bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial and socioeconomic disparities among patients with chronic lymphocytic leukemia: Analysis of Surveillance, Epidemiology, and End Results program data.
Authors: Kittai Adam , Huang Ying , Fisher James L. , Bhat Seema , Grever Michael R. , Paskett Electra D. , Rogers Kerry Anne , Woyach Jennifer Ann 
Published: June 2022

7542 Background: Therapy for chronic lymphocytic leukemia (CLL) has changed dramatically over the past 20 years. With the cost of new therapies and rapid practice changes, it is unclear if patients (pts) are benefiting equally from this progress. We assessed Surveillance, Epidemiology, and End Results (SEER) program data to determine how race and socioeconomic status (SES) affect survival for pts with CLL. Methods: CLL cases reported to 18 SEER Program registries from 2006 – 2018 were included. Pt characteristics such as age at diagnosis (dx), sex, year (yr) of dx, race, and SES as determined by rural/urban census tract residence (RUCA), and neighborhood (as represented by the Yost Index, a composite measure of 7 variables assessing different aspects of the SES of a census tract) were collected and analyzed. Multivariable cox regression (MVA) was used to determine adjusted odds of survival. Two separate databases were utilized, one which included data to 2018, and another which contained SES data but only had data available to 2016. Results: 46,605 cases from 2009 – 2018 were identified without SES data. The median age was 70 yrs, 60% were male, and there was an even distribution of patients diagnosed with CLL annually from 2009 – 2018. Of the cases with race reported, 89.9% were white, 7.3% Black, 2.4% Asian/Pacific islander, and 0.3% American Indian/Alaska Native. After a median follow up of 47 months, the median 3, 5, and 10 yr overall survival (OS) was 79.5%, 69.5%, and 48.8%, respectively. MVA showed Black race (HR 1.5, 95% CI 1.4 – 1.6) as the strongest independent prognostic variable for worse OS controlling for yr of dx, suggesting race was a significant factor in OS in the era of modern therapies. Using the linked RUCA and Yost tertiles for SES, 47,867 cases of CLL from 2006 – 2016 were analyzed. Median age, sex, and race distribution were similar to the prior analysis. MVA showed American Indian/Alaska Native, and Black race as independent prognostic variables for worse OS, and Yost group 2 and 3, representing higher SES, were found to be significant independent prognostic variables for improved OS (Table 1). In this analysis, race remained an independent variable for worse OS after controlling for SES. Conclusions: Black race and low SES are prognostic of OS in CLL. Further research is needed to determine whether this is due to access to therapy, quality of care, social determinants of heath, or disease biology.[Table: see text]
Quality-adjusted time without symptoms or toxicities (Q-TWiST) analysis of ZUMA-7, a randomized controlled trial of axicabtagene ciloleucel versus standard of care for second-line large B-cell lymphoma.
Authors: Kersten Marie José , Qiao Yao , Shah Ruchit , Solem Caitlyn , Snider Julia , To Christina Ann , Cheng Paul , Spooner Clare , Perales Miguel-Angel 
Published: June 2022

7555 Background: Quality of life (QoL) post cancer therapy is increasingly important. We conducted a Q-TWiST analysis to compare the quality-adjusted survival of axicabtagene ciloleucel (axi-cel, a chimeric antigen receptor T-cell therapy) versus standard of care (SOC) among relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients enrolled in ZUMA-7 (NCT03391466), a Phase 3, randomized, open-label, multicenter study. ZUMA-7 met its primary endpoint of event-free survival; events were defined as death, progression, or new lymphoma therapy. Methods: Overall survival (OS) in the intention-to-treat (ITT) cohort was partitioned into 3 mutually exclusive health states as measured through a median follow-up duration of 23.5 months (m): time with grade 3/4 adverse events (AE) before an event (TOX); time without symptoms from events or toxicity (TWiST); and time after event (REL). Q-TWiST was calculated as the average time spent in each state, weighted by state-specific QoL utility (u, ranging from 0 to 1), assuming a base case u(TOX)=0.5, u(REL)=0.5, u(TWiST)=1. Threshold analyses assessed the mean Q-TWiST differences between axi-cel and SOC by varying u(TOX) and u(REL) from 0 to 1. Relative gains for axi-cel (axi-cel Q-TWIST gain divided by mean SOC OS) ≥15% were considered “clearly clinically important” using published norms. Nonparametric bootstrap 95% confidence intervals (CI) were computed. Subgroup analyses were performed for relapse status and age. Sensitivity analyses varying the follow-up duration from 3 to 37.7m were explored. Results: For the ITT cohort (n=359), mean time spent in TOX and TWiST was significantly longer for the axi-cel cohort compared to SOC, and mean time spent in REL was significantly shorter for axi-cel (Table). Using the base case, quality-adjusted survival was significantly longer for axi-cel by 3.7m, representing a 21.9% relative gain. In threshold analyses, the difference in Q-TWiST ranged from 1.2m (u(TOX)=0, u(REL)=1) to 6.2m (u(TOX)=1, u(REL)=0) in favor of axi-cel. Q-TWiST gains favored axi-cel across all subgroup analyses. Q-TWiST gains from axi-cel increased with longer follow-up. Conclusions: Axi-cel was associated with statistically significant and “clearly clinically important” gains in quality-adjusted OS vs. SOC in R/R LBCL, regardless of the relative decline in QoL associated with treatment toxicity, disease progression, or additional cancer treatment.[Table: see text]
Bendamustine rituximab (BR) versus ibrutinib (Ibr) as primary therapy for Waldenström macroglobulinemia (WM): An international collaborative study.
Authors: Abeykoon Jithma P. , Kumar Shaji , Castillo Jorge J. , D'Sa Shirley , Kastritis Efstathios , Durot Eric , Uppal Encarl , Morel Pierre , Paludo Jonas , Tawfiq Reema , Sarosiek Shayna , Ogunbiyi M Olabisi , Cornillet-Lefebvre Pascale , Kyle Robert A. , Delmer Alain , Gertz Morie A. , Dimopoulos Meletios A. , Treon Steven P. , Ansell Stephen M. , Kapoor Prashant 
Published: June 2022

7566 Background: Parenteral limited-duration BR chemoimmunotherapy and continuous orally administered Ibr, a Bruton tyrosine kinase inhibitor, dominate the treatment landscape of WM, a rare B cell lymphoma. No trials have assessed the comparative effectiveness of these 2 vastly different approaches. We conducted a multiinstitutional, international, collaborative study to compare BR and single-agent Ibr in patients (pts) with treatment naïve (TN) WM. Methods: Data from 347 pts with active TN WM, seen between 2011 and 2021 in the US and Europe, were analyzed. The pts on rituximab maintenance were excluded. The modified IWWM-6 criteria (based on IgM alone) were used for response assessment. All time-to-event analyses were performed from the frontline therapy initiation, using the Kaplan-Meier method. Results: The median age of the pts treated with BR (n=208) and Ibr (n=139) was 66 (range 40-86) years (y) and 69 (39-97) y, respectively, (p=0.005). With a median follow up of 4.2 y (95% CI 3.8-4.5), the 4-y progression free survival (PFS) was 73% in each group, p=0.6, and 4-y overall survival (OS) was 94% (95% CI 91-98) in the BR group versus ( v) 82% (95% CI 75-90) in the Ibr group, p=0.01. In a bivariate analysis adjusting for age and the treatment type, only age emerged as a predictor for OS (HR 7.2, p=0.0001). Therefore, a 1:1 age-matched analysis of 246 pts who received Ibr (n=123) or BR (n=123) was performed. Pts with a known MYD88WT status who had received Ibr and their age matched controls on BR were excluded. The international prognostic scoring system (IPSS) WM was comparable between the 2 groups (Table). A higher proportion of pts on BR attained very good partial or deeper response (≥VGPR) as the best response in comparison to the pts on Ibr (Table). The 4-y PFS for the BR and Ibr groups was similar [72% (95% CI 63-82) v 78% (95% CI 70-87), p=0.14] and 4-y OS was 95% (95% CI 91-99) with BR v 86% (95% CI 80-93) with Ibr (p=0.3). Premature discontinuation, during active treatment, due to adverse effects (AEs) or lack of response was noted in 13% and 33% of pts on BR and Ibr, respectively. A detailed assessment of the AEs will be presented at the meeting. Conclusions: Both BR and Ibr lead to comparable outcomes in pts with TN WM, although deeper responses are attained with BR. These findings require confirmation in prospective studies. For pts who harbor MYD 88L265P mutation, selection between the 2 approaches should be dictated by their potential toxicities, pt comorbidities, pt/clinician preference (parenteral fixed-duration v continuous oral) and access to therapies. [Table: see text]
A phase II, multicenter, single-arm study of parsaclisib, a PI3Kδ inhibitor, in relapsed or refractory follicular lymphoma in China: Updated data from the study.
Authors: Zheng Zhong , Zhang Huilai , Zhou Keshu , Zhou Hui , Zhang Li , Li Caixia , Zhou Min , Qian Wenbin , Li Zhiming , Zhang Qingyuan , Cheng Ying , Liu Peng , Li Zhenyu , Su Liping , Li Fei , Sun Xiuhua , Wang Jingwen , Gao Yuhuan , Zhao Xielan , Zhao Weili 
Published: June 2022

7574 Background: For Follicular lymphoma (FL) patients (pts) of 3rd or higher line, treatment options are limited. Parsaclisib is a potent, highly-selective, next-generation PI3Kδ inhibitor. Initial safety and efficacy data were previously presented (Zhong Zheng et al. ASH 2021; NCT04298879). Here, we report safety, efficacy and survival data of the multicenter, open-label phase 2 study of parsaclisib in 3rd or higher line FL pts in China. Methods: Key eligibility included, age ≥ 18 years, histologically confirmed FL grade 1, 2, or 3a, ≥ 2 prior systemic therapies, ECOG PS ≤ 2, and ineligible for hematopoietic stem cell transplantation (HSCT). Pts received parsaclisib 20 mg once daily (QD) for 8 weeks followed by 2.5 mg QD, till disease progression (PD), unacceptable toxicity, death or withdrawn consent. Prophylaxis for Pneumocystis jirovecii pneumonia (PJP) was required. Primary endpoint was objective response rate (ORR) evaluated by an Independent Review Committee (IRC) according to Lugano 2014 criteria, secondary endpoints included: duration of response (DOR), PFS, OS, and safety and tolerability. Results: As of the data cutoff date (Dec 12, 2021), 61 pts (median age: 50yr; male [n = 35, 57.4%]) were enrolled. Forty-eight pts remained on treatment and 13 pts had discontinued study treatment mainly due to PD (n = 11). With a median follow-up time 9.5 months (range 6.0-19.7months), the median duration of treatment was 251.0 days (range: 23.0-589.0 days). All 61 pts were evaluable for response, the ORR and complete response rate (CRR) were 86.9% (n = 53, 95% CI: 75.8-94.2%) and 31.1% (n = 19, 95% CI: 19.9-43.3%), respectively. The median time to response (TTR) was 8.0 weeks (95% CI: 7.9-8.0%), and the median DOR was not reached (95% CI: 9.2 months-NC), and 43 of 53 pts with CR or PR still retained CR or PR. As data cutoff, eleven (17.9%) pts had disease progression, the median PFS was not achieved. Three pts died data as data cutoff, the median OS was not achieved. Among the 61 treated pts, 48 (95.1%) pts experienced at least 1 treatment-emergent adverse events (TEAEs), with the most common TEAEs being neutrophil count decreased (49.2%), white blood cell count decreased (32.8%). Twenty-seven patients (44.3%) experienced grade ≥ 3 TEAEs, the most common grade ≥ 3 TEAEs was neutrophil count decreased (n = 10, 16.4%). Conclusions: Parsaclisib demonstrated promising efficacy, and acceptable safety profile. These results suggest that parsaclisib could benefit 3rd or higher line Follicular lymphoma patients. Clinical trial information: NCT04298879.
Prognostic value of early bone marrow MRD status in CAR-T therapy for myeloma.
Authors: Bansal Radhika , Baksh Mizba , Larsen Jeremy Todd , Hathcock Matthew , Dingli David , Stewart Keith , Kapoor Prashant , Kourelis Taxiarchis , Hayman Suzanne R. , Warsame Rahma M. , Fonseca Rafael , Bergsagel Peter Leif , Ailawadhi Sikander , Kumar Shaji , Lin Yi 
Published: June 2022

8022 Background: Bone marrow (BM) assessment of minimal residual disease (MRD) is being considered as a surrogate endpoint in clinical trials and is prognostic for survival in multiple myeloma (MM). Timing of BM assessment is variable across Chimeric Antigen Receptor T cell (CART) therapy trials and differs from standard of care practice. BM myeloma cell clearance can be detected by month 1 post CART, even before serum immunofixation becomes negative. BM is still hypocellular at month 1, thus prognostic value of MRD negative (MRDneg) at this timepoint is unclear. We examined impact of Day 30 MRD status in patients (pts) who received CART at Mayo Clinic. Methods: Medical records were reviewed retrospectively for MM pts who received CART between 8/2016 and 6/2021. PFS and OS were plotted by Kaplan-Meier method. Results: Sixty MM pts received CART and had BM biopsy at month 1. Median age was 62 yrs, 53% were male, and 78% were BM MRDneg by flow cytometry. Baseline demographics were similar between MRDneg and MRD+ (Table). Overall, 85% (40/47) who were month 1 BM MRDneg had i/u FLC<normal. Patients who achieved CR/sCR had higher rates of BM MRDneg (100% vs 61%, p<0.001) and i/u FLC< normal (89% vs 58%, p<0.001). At month 1, 24/60 (40%) pts had hypocellular BM. Serial BM samples at month 3 (n=35), 6 (n=28) and 12 (n=23) showed MRDneg rate of 93% (25/27), 56% (9/16) 58% (7/12), respectively.. Rate of hypocellularity was 54% (19/35), 32% (9/28) and 30% (7/23), respectively. Among the MRDneg/hypocellular pts at month 1, hypocellular BM was seen in 8/11 (73%) pts at month 3 and 2/4 (50%) pts at month 6 and 12. Compared to MRD+, pts who had BM MRDneg at months1 had longer PFS (Table). PFS was not statistically significantly different between pts who had BM MRDneg and were either hypocellular or not. MRDneg pts with i/u FLC<normal at months1 had better median PFS compared to those who did not. (MRD+:2.9 months (1.2-NR). MRDneg/FLC>normal: 4.9 months (2.3-NR). vs MRDneg/FLC<normal:17.9 months (11.8-NR), p<0.0001). Conclusions: Hypocellular BM is common in the 3 months post CART. Regardless of BM cellularity, BM MRDneg at month 1 correlates with deep response and prolonged PFS. Majority of BM MRDneg pts at month 1 also had FLC<normal. BM MRDneg status and FLC normalization were associated with longer survival. Our data support the continued evaluation of BM early post CART infusion as a prognostic tool. [Table: see text]
Determinants of overall survival (OS) of primary plasma cell leukemia (pPCL): A National Cancer Database (NCDB) analysis of years 2004 to 2009.
Authors: Landau Kevin Scott , Mowery Kelsey Lynn , Liang Hong , Fu Chieh Lin , Chaulagain Chakra Pani 
Published: June 2022

8066 Background: Outcome data for pPCL is limited due to the rare & aggressive nature of the disease. In this retrospective analysis, we utilized NCDB to identify factors contributing to 1 & 5-year OS of pPCL patients treated at CoC-accredited facilities across USA. Methods: Using the NCDB, we identified N= 325 pPCL patients diagnosed between 2004-2009 after excluding entries missing relevant values. Univariate analysis was used to summarize & assess the potential survival factors individually & multivariate Cox regression analysis with backward elimination (using significance level of p<0.05) was utilized to identify the independent survival factors. Kaplan-Meier (KM) survival curves of patient cohort were also produced. SAS version 9.4 was used to analyze the data. Results: Multivariate Cox regression analysis with backward elimination method revealed that there were 4 significant independent survival factors including sex, Charlson-Deyo Comorbidity Index (CCI), facility type, and insurance, while age & year-of-diagnosis were not independent survival factors (Table). Male patients were more likely to die compared to female patients (HR=1.40, p=0.005); patients with CCI ≥1 had higher chance to suffer death compared to patients with CCI= 0 (HR=1.52, p=0.002); patients not treated at an academic center (AC) had lower survival compared to those treated at ACs (HR=1.35, p=0.001); and patients without private insurance (PI) were more likely to suffer death compared to those with PI (HR=1.54, p=0.001). The 1 & 5-year survival rates for whole cohort were 51.3% (95%CI: 45.8%-56.8%), and 18.9% (95%CI: 14.6%-23.2%) using KM estimate, respectively. Only 6/325 =1.8% patients underwent autologous hematopoietic stem cell transplant (HSCT). Detailed analysis will be presented. Conclusions: In this large analysis of pPCL patients, we identified that being female, having less comorbidities, getting treatment at ACs, and having PI had significantly greater OS. Overall, pPCL is associated with low survival rates both at 1 & 5-years and HSCT may be enormously under-utilized for pPCL patients in the real world setting. [Table: see text]
Monitoring PD-L1 expression on circulating stromal cells in blood predicts PFS and OS in patients with metastatic NSCLC treated with PD-L1/PD-1 immunotherapy.
Authors: Moran Jillian , Adams Daniel L , Lopez Bravo Pablo , He Jianzhong , Qiao Yawei , Xu Ting , Liao Zhongxing X. , Gardner Kirby P , Tang Cha-Mei , Lin Steven H. 
Published: June 2022

8535 Background: Cancer Associated Macrophage Like cells (CAMLs), a circulating stromal cell found in cancer patients (pts) blood, are phagocytic giant macrophages that appear to parallel the inflammatory PD-L1 state of the tumor microenvironment. Previously, we demonstrated in local non-small cell lung carcinoma (NSCLC), CAML PD-L1 expression is dynamic and predicts response to PD-L1/PD-1 immunotherapies (IMTs) following sequential sampling before and after chemotherapy (chemo) induction (̃30days) based on progression free (PFS) & overall survival (OS). However this has not been tested in metastatic NSCLC (mNSCLC). Here,we report the results of monitoring PD-L1 expression in CAMLs before and after chemo induction (̃30 days) to evaluate its predictive value in mNSCLC pts treated with or without IMT. Methods: A single blind multi-year prospective study was undertaken to test the relationship of PD-L1 expression in CAMLs to PFS & OS, pre & post chemo induction, in recurrent mNSCLC with (n = 41) or without (n = 41) additional anti-PD-L1/PD-1 IMTs. This included three IMTs: atezolizumab (n = 4), nivolumab (n = 8) or pembrolizumab (n = 29). We recruited 82 pts with pathologically confirmed recurrent mNSCLC prior to treatment for newly recurrent metastatic disease. Blood samples (15 mL) were taken at Baseline (BL), prior to chemo, and ̃30 days after chemotherapy (T1). Blood was filtered by CellSieve filtration & CAMLs’ expression scored as a binary high/low, to evaluate PFS & OS hazard ratios (HRs) by censored univariate & multivariate analysis at 18 months. Results: CAMLs were found in 97% of all tested samples, 94% at BL & 100% at T1. CAML PD-L1 at BL was found not to be associated with PFS or OS in pts treated with chemo alone (PFS p = 0.620 & OS p = 0.673) or chemo+IMT (PFS p = 0.353 & OS = 0.477) at 18 months. At T1, high CAML PD-L1 in pts treated with chemo alone had no significantly different PFS (HR = 1.3, p = 0.694) or OS (HR = 1.6 p = 0.503). However, high CAML PD-L1 at T1 in pts treated with chemo+IMT had significantly better PFS (HR = 3.1, 95%CI = 1.3-7.3, p = 0.019), and OS (HR = 3.4, 95%CI = 1.4-8.3, p = 0.014). Further subtyping & analysis is ongoing to evaluate PFS and OS at 24 months. Conclusions: Our data suggests that in mNSCLC, PD-L1 expression in circulating CAMLs dynamically upregulates after induction with chemotherapy and appears to predict patients with increased benefit to PD-L1/PD-1 IMTs, though additional studies are needed to validate these findings.
A phase II study of durvalumab (MEDI4736) immediately after completion of chemoradiotherapy in unresectable stage III non–small cell lung cancer: TORG1937 (DATE study).
Authors: Nakamichi Shinji , Kubota Kaoru , Misumi Toshihiro , Murakami Shuji , Kondo Tetsuro , Okamoto Isamu , Minato Koichi , Harada Daijiro , Isobe Kazutoshi , Itani Hidetoshi , Takata Saori , Wakui Hiroshi , Misumi Yuki , Ikeda Satoshi , Asao Tetsuhiko , Inoue Takeo , Hosokawa Shinobu , Kobayashi Yumiko , Takiguchi Yuichi , Okamoto Hiroaki 
Published: June 2022

8536 Background: Concurrent chemoradiotherapy followed by durvalumab maintenance for up to 12 months is the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). However, the best timing of starting durvalumab after completion of chemoradiation has not been identified. Progression-free survival (PFS) and overall survival (OS) were better in the subgroup of patients administered durvalumab within 14 days after last radiation to randomization according to the PACIFIC study (Antonia SJ, et al. 2017, 2018 NEJM). Methods: This study was a prospective, single-arm, multicenter, phase II clinical trial. Eligibility criteria included patients with unresectable stage III NSCLC, ECOG PS 0-1, age < 75 years old. Patients who did not have disease progression after definitive concurrent chemoradiotherapy (CCRT) (chemotherapy: 2 cycles of platinum-based doublet chemotherapy, radiotherapy: 60 Gy/30 Fr) received durvalumab (10 mg/kg, every 2 weeks for up to 12 months) from the next day (allowed up to 5 days) after last radiation. The primary endpoint was 1-year PFS rate from registration assessed by an independent review committee. The planned sample size was 47 with a threshold value of 50% based on results of the PACIFIC study, an expected value of 63%, one-sided alpha of 20% and power of 80% in 1-year PFS rate. Results: From January 2020 to August 2020, 50 patients were enrolled from 16 institutions and 47 patients were evaluable for efficacy and safety. Forty-two patients received durvalumab maintenance therapy. Patient characteristics were: male/female 41/6; median age 65 (range 42-75); ECOG PS 0/1 28/19; IIIA/IIIB/IIIC 19/21/7. The 1-year PFS rate from registration was 75.0% (60% CI: 69.0 to 80.0). The 1-year OS rate from registration was 97.7% (95%CI: 84.6 to 99.7). ORR, median PFS and median OS were 78.7%, 14.2 months (95%CI: 13.4 to not reached (NR)) and NR, respectively. Grade 3/4 adverse events were pneumonitis (4.3%), neutropenia (44.7%), febrile neutropenia (4.3%). There was no treatment-related death. Conclusions: Our study met the primary endpoint. Durvalumab can be safely administered immediately after completion of CCRT for patients with unresectable stage III NSCLC, no additional or unexpected toxicity occurred as a reference to the PACIFIC study. Clinical trial information: jRCTs031190117.