bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anthracycline-related cardiotoxicity among patients with lymphoma: Systematic review and meta-analysis.
Authors: Abu Rmilah Anan Abdelmoti , Kailash Vidur , Farooqui Naba , Jang Sae , Ruddy Kathryn Jean , Armenian Saro , Lenihan Daniel John , Loprinzi Charles L. , Herrmann Joerg 
Published: June 2023

e19517 Background: Anthracycline-induced cardiotoxicity (AIC) is a well-known phenomenon, but event rates and predictors may not be as robust as commonly perceived. We performed a systematic review and meta-analysis to elucidate AIC definitions, incidence rates and predictors. Methods: 5323 reports were identified via searching Medline, Embase, and Scopus. Inclusion criteria for full text review included minimum of 100 lymphoma patients receiving ACs; median/mean follow up of at least 12 months; and specified evaluation of left ventricular ejection fraction. We investigated the definition, reported incidence, and predictors of AIC including subclinical AIC as detected by decrease in left ventricular systolic dysfunction. Meta-analysis was performed with Meta-analyst software with random effects model. Results: A total of 19 studies were included in the analysis. The overall incidence of AIC in 13926 patients was 13.8% (95% CI 4.8-22.8, I2 99.6% p < 0.001) at a mean/median follow-up ranging from 1 to 8 years. Subclinical AIC was seen in 8.2% of 5464 patients (95% CI 6.4 to 10%, I2 78.9%, p < 0.001) at a mean/median follow-up ranging from 1 to 20 years. Subclinical AIC is defined in most studies as asymptomatic decrease in LVEF by 10-15% from baseline of 50-55%. Older age, increasing AC dose or number of cycles, GLS (global longitudinal strain), and prior comorbidities such as CAD, HTN, DM and dyslipidemia were found to predict AIC. However, Heterogeneity was seen in definition of AIC, risk factor assessment and follow-up protocol, which limited the extent of correlative analyses for cardiotoxicity predictors. Conclusions: The overall incidence of clinical HF and subclinical AIC among lymphoma patients was 13.8% and 8.2% respectively. Older age, increasing AC dose or number of cycles, GLS, and prior comorbidities such as CAD, HTN, DM and dyslipidemia were found to predict AIC.
Feasibility of CAR-T in very old patients with relapsed/refractory diffuse large B-cell lymphoma.
Authors: Rozental Alon , Chavez Julio C. , Sehovic Marina , Locke Frederick L. , Lazaryan Aleksandr , Nishihori Taiga , Khimani Farhad , Jain Michael D. , Shah Bijal D. , Extermann Martine 
Published: June 2023

e19521 Background: Chimeric antigen receptor T-cell therapy (CAR-T) has shown great efficacy in older relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) patients (pts). Pivotal trials have shown similar progression free survival (PFS) and overall survival (OS) between older and younger pts, and no difference in the incidence of cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), or grade 3-4 hematologic and non-hematologic toxicities. Nevertheless, there are limited reports in the literature concerning very old pts (≥75 years) receiving CAR-T for R/R DLBCL, and especially real world data in correlation with co-morbidities. Methods: We conducted a retrospective, single center analysis, including R/R DLBCL pts who underwent apheresis for CAR-T at 75 and older. We assessed co-morbidities by Cumulative Illness Rating Scale (CIRS-G) tool which set a score of 0-4 on all organ systems according to severity, and polypharmacy at time of apheresis, defined as ≥5 medications per day. We analyzed baseline characteristics, response rates, toxicity, and survival outcomes (PFS and OS). Results: A total of 47 pts were referred for CAR-T treatment. Median age at apheresis was 76.6 (75-86) years. Most of these pts received first-line treatment with full or attenuated dose R-CHOP (89%). However, 20 pts (42.5%) had refractory disease, and those achieving PR/CR had a median time to relapse of 13 months. Thirty-two pts (68%) were referred for CAR-T with refractory disease. Six pts died before receiving the CAR-T infusion due to PD. Characteristics of 41 pts receiving CAR-T infusion divided into subgroups of pts with CIRS-G categories 3-4 and pts with polypharmacy are shown in the table. Conclusions: CAR-T in very old (≥ 75 years) R/R DLBCL is feasible with no increased toxicity. While efficacy is important, the preliminary survival analysis seems suboptimal. At 1-year follow-up only a third of pts are alive. Severe co-morbidities or polypharmacy did not impact response or survival. Most deaths were due to disease progression, these outcomes might be attributed to the high rate of refractory disease. [Table: see text]
Comparative efficacy of zanubrutinib (ZANU) versus rituximab (RTX) in relapsed marginal zone lymphoma (MZL): Matching-adjusted indirect comparison (MAIC).
Authors: Thieblemont Catherine , Wang Kaijun , Keeping Sam , Zhang Ina , Yang Keri , Tang Boxiong , Mohseninejad Leyla 
Published: June 2023

e19526 Background: ZANU is a Bruton tyrosine kinase inhibitor that has been evaluated for relapsed/refractory MZL in two phase 2, single-arm (MAGNOLIA, n=66, NCT03846427; BGB-3111-AU-003, n=20, NCT02343120). At 28 and 35 months of study follow-up in MAGNOLIA and BGB-3111-AU-003, respectively, median progression-free survival (PFS) and overall survival (OS) were not reached. Here, we conducted an unanchored MAIC to estimate relative treatment effects of ZANU vs RTX, a commonly used treatment for patients with relapsed MZL. Note the comparison was restricted to the relapsed population because RTX refractory patients would not be retreated with RTX. Methods: The MAIC was performed using pooled individual patient-level data from MAGNOLIA and BGB-3111-AU-003. Study level-data of RTX in relapsed patients were used from CHRONOS-3 (Özcan et al., Ann Oncol 2021) which was identified as the most suitable comparator study via a systematic literature review. A logistic propensity score model was used to estimate weights for patients in ZANU trials such that their weighted mean baseline characteristics matched those of CHRONOS-3. The following characteristics were identified as key prognostic factors and included in the base case propensity score model: prior lines of therapy, MZL subtype, relapse after prior therapy, and age. Sensitivity analyses incorporating additional characteristics were not possible owing to a lack of reporting from CHRONOS-3, but the impact of each covariate in the base model was explored via a leave-one-out analysis. Comparisons were conducted for OS, PFS, and objective response rate (ORR) by independent review committee using weighted statistical models, with relative treatment effects presented as hazard ratios (HRs), odds ratios (ORs), and 95% CIs. Results: After applying weights estimated from the base case propensity score model, the effective sample size (ESS) for ZANU was 39. ZANU reduced the risk of progression (HR 0.29; 95% CI 0.13–0.65) and had a higher probability of response (OR 5.09; 95% CI: 1.84–14.08) when compared with RTX (Table). OS was comparable for ZANU and RTX, which is consistent with the survival expectancy for indolent lymphomas. The leave-one-out analysis showed that removing any of the characteristics from the propensity score model yielded comparable results. Conclusions: MAIC results suggest ZANU is associated with improved PFS and ORR compared with RTX in relapsed MZL. [Table: see text]
Matching-adjusted indirect comparison (MAIC) of zanubrutinib (ZANU) versus ibrutinib (IBRU) in relapsed/refractory marginal zone lymphoma (R/R MZL).
Authors: Thieblemont Catherine , Wang Kaijun , Keeping Sam , Zhang Ina , Yang Keri , Tang Boxiong , Mohseninejad Leyla 
Published: June 2023

e19527 Background: ZANU is a Bruton tyrosine kinase inhibitor (BTKi) that has been evaluated for the treatment of R/R MZL in two phase 2, single-arm trials (MAGNOLIA, n=66, NCT03846427; BGB-3111-AU-003, n=20, NCT02343120). At 28 and 35 months of study follow-up in MAGNOLIA and BGB-3111-AU-003, respectively, median progression-free survival (PFS) and overall survival (OS) were not reached. IBRU, a first-generation BTKi, has also been evaluated for R/R MZL in a phase 2, single-arm trial (PCYC-1121, n=60 [Noy et al., Blood 2017; Noy et al., Blood Adv 2020]). Here, we conducted an unanchored MAIC to estimate the comparative efficacy of ZANU vs IBRU in R/R MZL. Methods: The MAIC utilized study-level data from PCYC-1121 and pooled individual patient-level data from MAGNOLIA and BGB-3111-AU-003. A logistic propensity score model was used to estimate weights for patients in the ZANU trials so that weighted mean baseline characteristics matched those in PCYC-1121. The following characteristics were identified as key prognostic factors and included in the base case propensity score model: number of prior lines of therapy, MZL subtype, response to prior therapy, and age. A sensitivity analysis was conducted including additional characteristics (B symptoms, time since last therapy, prior anti-CD20 therapy, bulky disease [>5cm], and lactate dehydrogenase above normal). Comparisons were conducted for OS, PFS, and objective response rate (ORR) by independent review committee using weighted statistical models with relative treatment effects presented as hazard ratios (HRs), odds ratios (ORs), and 95% CIs. Results: After applying weights estimated from the base case propensity score model, the effective sample size (ESS) for ZANU was 68 (Table). Compared with IBRU, ZANU reduced the risk of progression (HR 0.38; 95% CI 0.21–0.69) and was associated with a higher ORR (OR 2.37; 95% CI: 1.13–4.96). OS was comparable for ZANU and IBRU, which is consistent with expectations for indolent lymphomas. The sensitivity analysis accounting for additional prognostic factors suggested the two treatments were comparable across all outcomes, owing in part to the low ESS (24) for ZANU associated with the expanded model. A leave-one-out analysis showed improved PFS (HR 0.33–0.45) for ZANU when excluding B symptoms, time since last therapy, or bulky disease from the expanded model. Conclusions: This MAIC demonstrated ORR and PFS benefits for ZANU vs IBRU in R/R MZL. [Table: see text]
CAR-T cells targeting CD38 and LMP1 and anti-tumor activity against NK/T cell lymphoma.
Authors: Li Hongwen , Shi Zhuangzhuang , Gao Yuyang , Li Zhaoming , Zhang Mingzhi 
Published: June 2023

e19529 Background: Natural killer/T-cell lymphoma (NKTCL) is an aggressive lymphoma with poor prognosis. In the past decade, chimeric antigen receptor transduced T (CAR-T) cell therapy has been a promising strategy against hematologic malignancies. Researchers have evaluated the efficacy of CAR-T cell targeting CD38 in multiple myeloma and NKTCL. LMP1 may induce a malignant transformation in B cells and epithelial cells, making it a non-negligible molecule in NKTCL. These suggest the potential clinical administration of CD38 and LMP1 targeting therapy. Methods: Four second-generation CAR-T cells including two single-targeted CAR (CD38-CAR and LMP1-CAR) and two tandem CAR (CD38-LMP1 Tan CAR 1 and Tan CAR 2) were constructed. Then the effects of four CAR-T cells on NKTCL cells were evaluated both in vitro and in vivo. Results: Four CAR-T cells could effectively eliminate malignant target-positive NKTCL cells in vitro. They could be activated and produce inflammatory cytokines in a target-dependent manner. Stimulated by CD38+LMP1+ NKTCL cells, two Tan CAR-T cells produced more IL-13, Granzyme B, IFN-γ and TNF-α than LMP1-CAR-T cells. In vivo test showed that CAR-T cells also exhibit significant anti-tumor effects in a xenotransplant NKTCL mice models. Two Tan CAR-T cells showed higher cytolytic activity against CD38+LMP1+ NKTCL cells than single-targeted CAR-T cells both in vitro and in vivo. Conclusions: We explored the feasibility of CAR-T cell therapy targeting both CD38 and LMP1 molecule. Our results indicated a promising effective therapeutic strategy for NKTCL.
Synergistic anti-tumor activity of the mTOR inhibitor everolimus and gemcitabine for the treatment of peripheral T cell lymphoma.
Authors: Huang Ling , Zhang Fen , Pang Diwen , Teng Yan , Jiang Xinmiao , Pan Lu , Sun Yichen , Guo Hanguo , Wei Xiaojuan , Chen Feili , Liu Sichu , Lin Caidi , Wang Yali , Wang Ning , Liang Zhanli , Huang Yilan , Ong Choon Kiat , Zhang Qingling , Tan Jing , Li Wenyu 
Published: June 2023

e19538 Background: Patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) have dismal prognosis and limited treatment options. The mTOR inhibitor everolimus or gemcitabine as a single agent regimen had limited clinical efficacy in patients with R/R PTCL. Therefore, investigation of active combination therapies with everolimus for T cell lymphoma needs to be investigated. Methods: A retrospective analysis of 24 R/R PTCL patients were treated with everolimus and gemcitabine from December 2017 to March 2021. The primary endpoint was objective response rate (ORR). CellTiter Glo and AnnexinV FITC/PI were utilized to determine cell viability and apoptosis, respectively. Results: Here we demonstrated that combination treatment of everolimus and gemcitabine is effective in treating R/R PTCL patients, achieving an ORR of 70.8%, with 45.8% complete response rate. The median time to response was 1.7 months. With a median follow-up time of 22.3 months (95% confidence interval[CI], 5.7-39.0), the median PFS of all patients was 9.9 months (95%CI, 0-20.81), the median DOR was 16.8 months for responders. Patients with best response of CR and PR achieved superior PFS (18.7 vs. 1.2 months, P = 0.0007) and OS (30.9 vs. 5.8 months, P = 0.021) than that with SD and PD. Grade 3 or 4 neutropenia, thrombocytopenia and anaemia occurred in 13 (29.2% grade 3 and 25.0% grade 4), 11 (8.3% grade 3 and 37.5% grade 4) and 7 (16.6% grade 3 and 12.5% grade 4) patients, respectively. Functional in vitro studies showed that combination treatment synergistically inhibited cell viability and induced apoptosis in PTCL cell lines. Mechanistically, transcriptomic profiling indicated that the synergistic effect was induced through the abrogation of MYC pathway. Conclusions: Collectively, our study sheds light on synergistic antitumor effect of combinatorial therapy, providing a potential therapeutic strategy for patients with R/R PTCL.
Outcomes with bendamustine lymphodepletion prior to brexucabtagene autoleucel for mantle cell lymphoma.
Authors: Chong Elise A. , Gerson James N. , Nasta Sunita Dwivedy , Landsburg Daniel J , Barta Stefan K. , Svoboda Jakub , Weber Elizabeth , Chong Emeline R. , Schuster Stephen J. 
Published: June 2023

e19540 Background: Brexucabtagene autoleucel (brexu-cel) is approved for relapsed/refractory mantle cell lymphoma (MCL). Cyclophosphamide/fludarabine for lymphodepletion (LD) is standard LD prior to brexu-cel. Due to a recent fludarabine shortage as well as institutional practice, we have utilized alternatives to fludarabine-based LD prior to brexu-cel, predominantly bendamustine. Bendamustine is an attractive option because it is included in the label for another anti-CD19 CAR T cell product. We report our institutional experience with bendamustine LD followed by brexu-cel. Methods: We retrospectively examined our institutional records for all patients with MCL who were treated with bendamustine LD followed by brexu-cel from 2020-2022. Progression-free survival (PFS) was analyzed with Kapalan-Meier survival analysis. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT criteria. Results: 16 patients received bendamustine followed by brexu-cel. Median age was 65 years (range: 54-76). Median number of prior therapies was 3 (range: 3-8). All patients (100%) had received a BTK inhibitor prior to brexu-cel. 14/16 (88%) received bridging therapy. 14/16 (88%) patients had CRS; 11/14 (79%) had grade 1-2 CRS and 3 (21%) had grade 3 or greater CRS. 5 (31%) patients had ICANS; 2 (40%) had grade 1-2 ICANS, and 3 (60%) had grade 3 or greater ICANS. 10 (63%) patients received tocilizumab, 8 (50%) received dexamethasone, and 3 (19%) received anakinra for management of CRS and/or ICANS. Best objective response rate (ORR) was 81% with 11 (69%) patients achieving CR. Median follow-up was 13.4 months. Estimated 6-month progression-free survival was 86% (95%CI: 54-96%) and 12-month progression-free survival was 63% (95%CI: 32-82). Conclusions: Bendamustine LD prior to brexu-cel for MCL is feasible, and, although these numbers are small, appears to have comparable outcomes to that reported in real world brexu-cel data (best ORR 90% with 82% CR rate, 6 month PFS estimate 69%, 12 month PFS estimate 59%; Y Wang et al. J Clin Oncol 2023) and ZUMA-2 outcomes (93% ORR with 67% CR rate, 12 month PFS estimate 61%; M Wang et al. NEJM 2020).
What differences in outcomes exist in Hispanic patients being treated for lymphoplasmacytic lymphoma and waldenstrom macroglobulinemia?
Authors: Huston-Cravens Jacob , Fierro Maria Elena , Liu Qianqian , Michalek Joel , Diaz Duque Adolfo Enrique 
Published: June 2023

e19541 Background: Lymphoplasmacytic Lymphoma (LPL) and Waldenstrom Macroglobulinemia (WM) are both rare diseases with little known about their longterm outcomes in ethnic minorities. Overall, the 5- and 10-year survival of this disease has improved over the last 60 years (Blood, PMID: 24948623), but few studies have explored outcomes in Hispanic (HI) patients. We analyzed demographics, treatment patterns and outcomes in patients diagnosed with LPL and WM comparing HI and Non-Hispanics (NH) in the US. Methods: Data was analyzed on LPL and WM patients in the US reported to the Surveillance, Epidemiology, and End Results (SEER) analyzing patient characteristics, age-adjusted incidence rate, and survival rate among HI and NH patients. Results: HI were diagnosed at a younger median age on both LPL and WM cohorts compared to NH (p <0.001). There was a higher percentage of HI patients diagnosed with LPL and WM before the age of 60 compared to that of NH (p <0.001). Regarding race of patients with LPL, most of both HI and NH patients identified as whites (94% vs 86%), followed by blacks (2% vs 6%). Regarding stage, a majority of both HI (50%) and NH (60%) patients diagnosed with LPL were Stage IV. In terms of radiation, 7% of HI patients with LPL received it, compared to 4% of NH patients (p=0.027). On survival analysis for LPL patients, the survival probability at 2, 5 and 10 years (y) of HI vs NH were similar. There was not an OS difference favoring HI/NH (p=0.49). On survival analysis for WM patients, the survival probability at 2, 5 and 10 y of HI vs NH were similar. The median survival time for patients with WM was similar between HI and NH patients and there was not OS difference favoring HI vs NH (p=0.16). On multivariate analysis for LPL and WM, those diagnosed over the age of 80 had worse OS compared to those younger than 60 (95% CI; 4.8-8.1 and 2-3.4, respectively). No OS benefit when adjusting for stage was observed for either LPL or WM. Conclusions: In LPL and WM patients HI patients were diagnosed at younger ages compared to NH for both LPL and WM, and more likely to be diagnosed before the age of 60. The median survival rates were similar between HI and NH patients diagnosed with both LPL and WM. These findings may be confounded by earlier diagnosis in HI patients; however, further studies are needed exploring biological ethnic differences to explain early diagnosis in LPL and WM among HI.
COVID-19 infection in patients on anti-CD20 monoclonal antibodies: Changes in clinical outcomes and management over time.
Authors: Ali Mohammad , Abdullah Hafez M , Ahmed Mamoon , Chaudhry Hammad , Khan Dawlat , Khalil Fouad , Wachira David , Bleeker Jonathan 
Published: June 2023

e19542 Background: As the COVID-19 pandemic progressed, survival of patients in the general population with COVID-19 improved over time. It is less clear based on current data whether patients on anti-CD20 therapy experienced similar improvement in outcomes over time. Methods: We performed a retrospective study of all patients aged ≥ 18 years diagnosed with COVID-19 while receiving anti-CD20 therapy for hematologic malignancy and/or rheumatologic indications at our center from January 2020-January 2022. Our primary endpoint was median overall survival (OS) and clinical outcomes stratified by date of diagnosis (“early cohort” = 03/01/20 to 12/31/20, “later cohort” = 01/01/21 to 10/15/21, and “latest cohort” = 10/16/21 to 01/16/22”). Secondary endpoints were to describe changes in the management of patients receiving anti-CD20 agents as the pandemic progressed and to assess independent predictors of OS in this population. Results: The median OS of 186 patients in the entire group was 13 months and the case fatality rate (CFR) was 23%. The CFR of admitted patients was 84%, whereas it was 16% for those who were not admitted. To examine trends over time, we compared 71 patients in the early cohort to 69 in the later cohort, and 42 patients in the latest cohort. The median OS of patients in the early cohort was 18 months (0.1-27) compared to 9 months (0-22) in the later cohort, and 8 months (0-20) in the latest cohort (P = 0.1884). The proportion of patients who received steroids was relatively consistent as the pandemic progressed with 45% in the early vs. 41% in the latest cohort. Fewer patients received remdesivir (31% for early cohort vs 21% for latest cohort) and convalescent plasma (13% for early cohort vs 2% for latest cohort) over time. The only baseline or treatment characteristics associated with adverse outcomes were receipt of steroids and anticoagulation, both of which were associated with an increased risk of death ((HR = 5.5, p = 0.002) and (HR = 2, p = 0.043 respectively)). Conclusions: Patients receiving monoclonal anti-CD20 antibody therapy had worse clinical outcomes than previously reported outcomes for the general population. OS did not significantly improve as the pandemic progressed; the phase of the pandemic with the shortest median OS was from 01/01/21 to 10/15/21 during the Delta SARS-COV-2 wave. Our data demonstrates an increased risk of death in patients on monoclonal anti-CD20 who experienced a COVID-19 infection and were treated with steroids, consistent with other reports.