bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety outcomes in adult patients with AML who achieved their first complete remission with GO prior to HSCT.
Authors: Bejanyan Nelli , Ho Vincent , Perales Miguel-Angel , Kebriaei Partow , Kaur Manmeet , Zhang Mei-Jie , D'Amico Paul G. , Purcell Simon , Dorman Stephanie , Vandendries Erik , Asomaning Kofi , Saber Wael 
Published: June 2024

e18504 Background: Gemtuzumab ozogamicin (GO) is approved in the US for the treatment of newly diagnosed and relapsed/refractory (R/R) CD33-positive acute myeloid leukemia (AML) in adults and pediatric patients of 1 month and older and 2 years and older, respectively. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for most adult patients with AML in first complete remission (CR1). Clinical studies have linked GO with hepatotoxicity and hepatic veno-occlusive disease (VOD); the risk of these events may be further elevated in patients receiving HSCT. This study aimed to characterize the toxicity after HSCT in adult patients with AML who were treated with GO prior to HSCT. These analyses look at outcomes in patients who were in CR1 at the time of HSCT. Methods: This non-interventional post-authorization safety study used de-identified healthcare data from the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Data were collected from adult patients in the US with newly diagnosed AML treated with GO prior to proceeding with HSCT. Data collection began on 01 September 2017, data cutoff was 04 July 2023. Results: We present data of 84 patients receiving HSCT for AML in CR1 from 19 centers with a median follow-up of 23.9 months (range, 3.0-49.7). Median age was 54.2 y (range, 18.7-74.5); 55% male. Total cumulative GO dose was 1-3 mg/m2 in 15 (18%), 4-6 mg/m2 in 15 (18%), 7-9 mg/m2 in 28 (33%) and ≥10 mg/m2 in 8 (12%) patients. Measurable residual disease (MRD) was undetectable in 50% (n=42) of patients after GO and 51% (n=43) of patients at the time of HSCT. Most patients (58%; n=49) received myeloablative conditioning and 57% (n=48) received HLA matched unrelated donor HSCT. Non-fatal VOD was reported in 6 (7%) patients, most cases were mild (n=5; 83%). Cumulative incidences of transplant-related mortality (TRM) were: 6 months, 7% (95% CI, 3-14); 2 years, 15% (95% CI, 7-25). The 2-year relapse rate was 26% (95% CI, 16-36%). Kaplan-Meier probabilities of leukemia-free survival (LFS) outcomes at 1 and 2 years were, 68% (95% CI, 57-78) and 59% (95% CI, 47-71), respectively. There were 22 deaths during the study, 10 (46%) from relapse of AML, no VOD-related deaths were observed. Conclusions: The use of GO prior to allogeneic HSCT appears to be safe with low rates of posttransplant VOD observed in patients with AML in CR1. TRM and survival outcomes are similar to historically reported rates. Clinical trial information: B1767034.
Trends on treatment patterns in patients with newly diagnosed AML: Preliminary findings from a real-world analysis.
Authors: Alessandrini Ester Rita , Moreira Jeverson , Simon Virginie , Mallet Oscar , Gamaoun Rihab , Péan Romane , Hamkoung Gauvain , Zuo Yue , Reppelin Théophile , Kertous Mehdi , Templier Alexandre , Mounedji Nadjat 
Published: June 2024

e18506 Background: In the last two decades, new therapeutic options have emerged to complement traditional intensive chemotherapy (IC) regimens in the treatment of Acute myeloid leukemia (AML). Hypomethylating agents (HMAs), the B-cell lymphoma 2 (BCL-2) protein inhibitor Venetoclax, and other targeted therapies are examples. Guideline-based treatment decisions are intricate, considering both patient fitness to IC and disease characteristics. AML real-word studies on treatment patterns typically focus on specific subpopulations (e.g., elderly or unfit patients), and few studies analyze broader populations. We analyzed an US electronic health records (EHR) database to describe AML treatment patterns. Methods: Study was designed as retrospective, descriptive analysis of deidentified secondary data from COTA database in the US. Data was abstracted for AML patients diagnosed for the first time between January 2017 and September 2022. Follow-up period (FP) was defined as the period starting at the diagnosis until the last information available for: death, or last contact, or the emergence of other malignancies. To improve descriptive analysis, treatment categories were classified accordingly: IC and non-IC. We conducted descriptive statistics (expressed as counts, percentages or means and medians [with SD or IQR]) for the different assessed features. Results: From the 3,500 patients included on the database, 1,436 were eligible for the analysis with a newly diagnosed AML disease after January 2017. Individuals’ age at diagnosis falls between 60 and 74 years old for 41% of the cohort with mean age of 64[15] years and 60% were followed on community centers. Male patients slightly outnumber female patients (53% and 47%, respectively). Primary AML accounted for 41% of the population and secondary for 28%. Mean time to first treatment after diagnosis was 14[42] days for the overall cohort, the main reason for the end of follow-up was death for 58% of individuals and 47% of the patients had a follow-up inferior to one year. While analyzing treatment patterns according to line of therapies (LoT) sequences, IC only was predominant for 30% of the population, followed by non-IC only for 28%. Remaining counts (42%) correspond to association of both categories. Most prevalent regimen on IC only group was High-dose Cytarabine monotherapy (HIDAC) (12%), and HMA (Azacitidine)+Venetoclax (27%) for the non-IC only group. Conclusions: Our preliminary and recent findings demonstrate that incidence of AML remains high in elderly groups. Despite the introduction of novel therapies, IC remains the predominant treatment approach for newly diagnosed AML patients. Our ongoing real-world analysis aims to assess a more detailed description of LoT sequences in AML population.
Predictors of mortality among adults with acute lymphocytic leukemia in relapse with tumor lysis syndrome during chemotherapy.
Authors: Adla Jala Saisree Reddy , Gadhiya Dhruvkumar , Sakthivel Hemamalini , Tummala Nayanika , Mal Madho , Dhaliwal Kanwar Bir Singh , Dandwani Mehndi , Ramphul Kamleshun , Chennapragada Suma Sri 
Published: June 2024

e18510 Background: Tumor lysis syndrome (TLS), a common complication of chemotherapy, can be an oncologic emergency involving various complications, such as electrolyte imbalance, triggering a higher risk of mortality. We aim to understand the predictors of death among Acute lymphocytic leukemia (ALL) patients in relapse who experienced TLS during their chemotherapy admission. Methods: Our study focussed on ALL adults in relapse, ages≥ 18 years, from the 2016-2020 National Inpatient Sample (NIS) undergoing chemotherapy who experienced TLS. Multivariate regression analyses helped evaluate the impact of several patient characteristics on all-cause mortality. Results: Initially, a total of 11710 patients with ALL in relapse were found who were undergoing chemotherapy. Among them, an estimated 930 (7.9%) experienced TLS. The mortality rate among TLS patients was 14.0%, as 130 deaths were reported. Higher odds of mortality were noted among Females (vs. Males, aOR 2.169, 95% CI 1.188-3.959, p=0.012), patients with events of acute kidney injury (AKI) (aOR 2.006, 95% CI 1.096-3.672, p=0.024), hypertension (aOR 5.582, 95% CI 2.969-10.494, p<0.01), cirrhosis (aOR 39.119, 95% CI 16.380-93.422, p<0.01), presence of hyperkalemia (aOR 3.366, 95% CI 1.605-7.063, p<0.01), or cardiac dysrhythmias (aOR4.630, 95% CI 2.063-10.391, p<0.01). Meanwhile, lower odds of mortality were seen among people with diabetes (aOR 0.386, 95% CI 0.157-0.951, p=0.039). No racial disparities were noted between Blacks (aOR 1.806, 95% CI 0.730-4.471,p=0.201) and Hispanics (aOR 1.870, 95% CI 0.900-3.887, p=0.094) compared to Whites. Similarly, smoking status (aOR 0.466, 95% CI 0.196-1.110, p=0.085), events of acidosis (aOR 1.012, 95% CI 0.494-2.074, p=0.974), and patients of ages ≥60 years(vs.<60 years, aOR 1.230, 95% CI 0.627-2.415, p=0.547) did not show any differences in mortality. Patients who died also had a more extended hospitalization (24.27 days vs. 20.15 days, p<0.01), with a more expensive stay (mean hospital charge $600779 vs. $418867, p<0.01). Conclusions: Our analysis confirms the burden of TLS in the prognosis of ALL patients undergoing chemotherapy. The mortality rate was higher for women and those with pre-existing comorbidities. However, people with diabetes have a lower risk, possibly due to close monitoring and prophylactic strategies. Notably, race, smoking status, acidosis, and age over 60 years did not show significant differences in mortality rates. Scaling the study to different healthcare organizations will help augment the sample size, assess the impact of treatment plans, and overcome limitations such as lack of disease duration, post-discharge follow-up, and potential diagnostic and coding errors.
The role of MDSCs in the development of bone marrow fibrosis.
Authors: Feng Qiutian , Huang Jian 
Published: June 2024

e18532 Background: Myelofibrosis is a type of myeloproliferative disorder, and research indicates that the immunosuppressive tumor microenvironment plays a significant role in the pathogenesis of myelofibrosis, with myeloid-derived suppressor cells (MDSC) being the primary inhibitory cells involved in shaping the tumor immune microenvironment. In this study, we used flow cytometry to detect the number of MDSC in the bone marrow of myelofibrosis patients, and the concentration of CCL2 in the supernatant of bone marrow MDSC cells of patients with myelofibrosis was detected by Elisa technique. Methods: In this study, we utilized flow cytometry to identify the number of Lin-HLA-DR-CD33+ labeled MDSC in the bone marrow of 109 myelofibrosis patients and 20 healthy individuals. Subsequently, we detected the CCL2 concentration in the cell culture supernatant of bone marrow MDSC cells from 42 patients with bone marrow fibrosis after stable culture using ELISA technique. Results: The results of flow cytometry revealed a significant increase in the percentage of MDSC in the bone marrow of myelofibrosis patients (15.16±6.25%) compared to healthy individuals (1.72±0.88%) (p<0.0001). Among them, the MDSC counts were 20.86±6.17% in PMF patients, 18.10±4.77% in post-ET MF patients, and 15.58±3.65% in post-PV MF patients, with no significant statistical difference in MDSC counts among the three groups.And them, the CCL2 concentration in the supernatant was 13.67±1.68 pg/ml for patients with MDSC count <5% (n=6), 36.36±11.88 pg/ml for patients with MDSC count between 5% and 10% (n=16), 55.12±9.71 pg/ml for patients with MDSC count between 10% and 20% (n=14), and 83.19±14.01 pg/ml for patients with MDSC count >20% (n=6). Conclusions: Research has shown that the number of MDSCs is elevated in patients with myelofibrosis compared to healthy individuals. We also found that as the MDSC count increased, the CCL2 concentration in the cell culture supernatant increased accordingly, suggesting that CCL2 may be involved in the proliferation and activation of MDSCs.
Long-term survival outcomes in patients with relapsed/refractory large B-cell lymphoma after treatment of relma-cel: 4-year follow-up in RELIANCE study.
Authors: Yang Haiyan , Guo Ye , Li Wenyu , Zou Dehui , Zhou Daobin , Wang Zhao , Zhang Mingzhi , Wu Jianqiu , Liu Hui , Xia Zhen , Yang Su , Zhou Zisong , Qin Yun , Song Yuqin , Zhu Jun 
Published: June 2024

e19001 Background: RELIANCE study (NCT04089215) demonstrated the efficacy and safety of relma-cel, a CD19-targeted chimeric antigen receptor T-cell product, in patients with heavily pre-treated relapsed/refractory large B-cell lymphoma (r/r LBCL). We previously reported efficacy of relma-cel, noting objective response rate (ORR) in 77.59% of patients (CRR 53.45%), 2-year progression-free survival (PFS) rate and overall survival (OS) rate were 38.8% and 69.3%, respectively. Herein, we aimed to update the long-term survival results for 4-year follow-up (FU). Methods: Study design was previously published. Eligible patients were adults with histologically confirmed r/r LBCL and had failed at least two prior lines of therapy, including an anti-CD20 monoclonal antibody and an anthracycline-based regimen. Patients were enrolled at 10 clinical sites in China and underwent lymphodepletion prior to receiving relma-cel at a single dose of 100 × 106 (n=27) or 150 × 106 (n=32) CAR+ T cells. The primary endpoint was ORR at 3-month, as assessed by investigators. Secondary endpoints were duration of response (DOR), PFS, OS and safety profiles. For this abstract, we collected the survival status and updated the survival outcomes. Results: From Nov 2017 to Dec 2019, a total of 68 patients were enrolled, and 59 received relma-cel infusion. Among 58 evaluable efficacy patients with 2-year FU, 31 achieved CR (CR group), 14 achieved PR (PR group) and 13 had no response (Non-responder group). As of Dec 18, 2023, with 48.1 months (95% CI, 37.75 to 49.38) of median FU, 25 patients were still alive, 18 were died (5 deaths in CR group, 5 in PR group and 8 in Non-responder group), and 15 patients were censored due to lost to FU including 7 lost within 2 years and 8 after 2 years. The median OS were not reached (NR), and 1-year and 2-year OS rate were reported previously. The update estimated landmark OS rates were 69.3% at 3-year and 66.7% at 4-year. The OS rates of CR group at each year were numerically higher than those of PR group and Non-responder group (87.1% v.s. 59.3% v.s. 30.8% at 3-year and 82.5% v.s. 59.3% v.s. 30.8% at 4-year; Table). Conclusions: Four-year FU results in RELIANCE Study suggested that, although heavily pretreated, the patients who had response, especially who achieved CR, may experience greater survival benefits, from relma-cel therapy. Clinical trial information: NCT04089215 . [Table: see text]
Cardiovascular adverse events in patients with cancer treated with chimeric antigen receptor (CAR) T-cell therapy: A meta-analysis of both controlled and single-arm clinical trials.
Authors: Myint Phyo Thazin , Kulasekaran Monika , Yasir Muhammad , Saleh Mohammed , Verghese Cherian 
Published: June 2024

e19006 Background: Chimeric antigen receptor (CAR-T) Chimeric antigen receptor (CAR) T-cell therapy presents a promising avenue in the treatment of hematological malignancies. However, the application of CAR-T cell therapy comes with a range of adverse effects, some of which are not fully understood yet. While previous research has primarily focused on immune effector cell-associated neurotoxicity (ICANs) and cytokine release syndrome (CRS), the cardiovascular safety profile of CAR-T cell therapy remains less defined. This meta-analysis assesses the incidence of cardiovascular (CV) events associated with CAR-T therapy, thereby providing critical insights into these events and guiding clinical decision-making. Methods: We conducted a Pubmed search of clinical trials evaluating the effect of CAR-T cell therapy in cancer patients with cardiovascular adverse events. For phase III trials, a quantitative assessment of Grade 3 or higher CV events was performed using the Review Manager (Rev-Man) Version 5.4 (The Cochrane Collaboration, 2020) and the results were reported as Odd Ratio (OR) with 95% Confidence Interval (CI). A fixed effect model was used. For phase I/II trials, the event rates were calculated for all-grade as well as grade 3 and higher CV adverse events. Results: A total of four Phase III clinical trials with 1345 patients were included for the comparison analysis. Among those trials, two involved multiple myeloma patients, and two involved large B cell lymphoma patients. The age range across trials was 20-83 years with a male-to-female ratio of 1.5:1. The analysis revealed that there was no statistically significant difference in Grade 3 or higher CV events between the CAR-T cell therapy and control (standard of care) groups: OR with 95% CI was 1.44 (0.73,2.82) (p=0.29). Grade 3 and above CV adverse event rates were 3.4% for the CAR-T and 2.1% for the control groups. Notably, there were two CV deaths in the CAR-T group and one CV death in the control group. Additionally, a total of 41 single-arm, Phase I/II clinical trials with 1479 participants were analyzed. Seven studies included solid cancers such as metastatic pancreatic cancer, biliary tract cancer and melanoma. The age range was 17-86 yr and male/female ratio was 1.5:1. Total all-grade CV adverse event rate was 21.83% and total grade 3 and above CV adverse event rate was 8.82%. There were eight CV deaths. Conclusions: There were significantly more CV adverse events reported in Phase I/II trials when compared to those reported in Phase III trials. This indicates that CV adverse events are important consequences of CAR-T cell therapy but are likely underreported in the Phase III clinical trials. Increased awareness and more standardized evaluation of CV adverse events of CAR-T is needed in the future clinical trials.
Efficacy and safety of mosunetuzumab-based regimens as first-line therapy in non-Hodgkin lymphomas: A systematic review of clinical trials.
Authors: Jumean Samer , Elemian Shatha , Aiman Wajeeha , Ali Muhammad Ashar , Ramahi Amr , Al Omour Bader , Shaaban Hamid Salim , Guron Gunwant K. , Hammad Munther , Maroules Michael 
Published: June 2024

e19013 Background: Bispecific antibodies (BsAbs) are emerging as a promising new immunotherapy modality in patients with lymphoma. Mosunetuzumab is a CD20xCD3 T-cell engaging bispecific monoclonal antibody that redirects T cells to eliminate malignant B cells, was first to receive approval for relapsed or refractory follicular lymphoma. Here, we report the safety and efficacy of Mosunetuzumab as a first line therapy in combination or monotherapy regimen in non-hodgkin lymphoma. Methods: A literature search was performed on PubMed with keywords for “Mosunetuzumab” AND “lymphoma”. The search was performed from the inception of data till 1/1/2024. A total of 237 articles were screened and three non-randomized clinical trials (nRCTs, N=124) were included. PRISMA guidelines were followed while conducting this systematic review. Results: In 3 clinical trials, 54 patients were treated with mosunetuzumab monotherapy, 40 with mosunetuzumab + cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and 30 with subcutaneous mosunetuzumab. 94 patients had diffuse large B-cell lymphoma (DLBCL), and 30 patients had follicular lymphoma. ORR, CR, and PR were reported in 56%, 43%, and 13% patients, respectively, treated with mosunetuzumab monotherapy in DLBCL. ORR, CR, and PR were reported in 87.5%, 85%, and 2.5% patients, respectively, treated with mosunetuzumab + CHOP in DLBCL. ORR, CR, and PR were reported in 96%, 83%, and 12.5% patients, respectively, treated with subcutaneous mosunetuzumab in follicular lymphoma. Neutropenia, thrombocytopenia, infections, and fatigue were common adverse effects given in the table. Conclusions: Mosunetuzumab with CHOP showed higher efficacy results and was well tolerated by most of the patients and can be an option to achieve high response rates in DLBCL. Subcutaneous mosunetuzumab was active in follicular lymphoma with manageable toxicity in follicular lymphoma. However, long-term results are needed to determine the durability of responses and long-term safety and survival rates with these regimens. [Table: see text]
A retrospective observational study of rapid titration of venetoclax (VEN) in patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).
Authors: Babalola Tijesuni , Ayers Emily C. , Douvas Michael G. , Foster Laahn , Densmore John , Williams Michael E. , Portell Craig Anthony 
Published: June 2024

e19018 Background: CLL and MCL can present with rapid disease progression that requires quick control. VEN is an oral, small-molecule inhibitor of BCL-2 that requires careful dose titration to avoid TLS. However, standard outpatient titration of VEN takes 29 days to reach max dose, with the low doses achieving little disease control. A common practice at our site is to rapidly titrate VEN to 100mg within 1 week with hospitalization for careful TLS monitoring and management. We present the safety and outcomes of 39 identified patients treated as such. Methods: The rapid VEN titration plan was: VEN 20mg x 2 days, 50mg x 2 days, then 100mg daily with q6-q8 hour monitoring of TLS labs plus ongoing IV hydration and allopurinol with or without rasburicase per clinical judgment. Most patients were treated in such manner if TLS did not occur. Clinically stable patients were typically discharged after 2 days of VEN 100mg, then continued weekly outpatient dose escalation to the 200mg and then the 400mg dose levels. If a patient was progressing on a Bruton's Tyrosine Kinase inhibitor, the inhibitor was often given concurrently with the early doses of VEN. Results: Patient characteristics are listed in the table. 23% (5 of 22) of patients with CLL and 35% (6 of 17) of patients with MCL had laboratory TLS (Howard SC, NEJM2011). In the patients with CLL, 2/5 were low risk for TLS, and in the patients with MCL, 3/6 were low risk for TLS. Only 4.5% (1 of 22) of CLL patients and no MCL patients had clinical TLS (Grade 2 creatinine elevation). In that specific patient, considered low risk for TLS, the elevated creatinine did not recover but was subsequently deemed secondary to Richter’s transformation involving the kidneys. No unexpected toxicity was observed outside of those typically associated with VEN and anti-CD20 antibody, when used. The mean number of days to reach 100mg was 6.5 days (quartile [Q] 1:5d; Q3: 10d), and the mean number of days to reach the planned VEN target dose was 18.8 with range (Q1:14d; Q3: 25d). Sixty-four percent of patients achieved the 400mg dose level. Conclusions: This single-institution retrospective analysis highlights the low rate of clinical TLS when using VEN with rapid titration in a controlled environment for high-risk patients needing rapid disease control. However, lab TLS occurred in low-risk patients treated in this manner, necessitating hospitalization despite low risk. No unexpected or additional toxicity was observed. [Table: see text]