bluuebunny/crossref_metadata_2025 huggingface dataset:
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]
Real-world Bruton tyrosine kinase inhibitor (BTKi) treatment patterns and outcomes among patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) in US community oncology practices.
Authors: Hou Jing-Zhou , Blanc Simon , Maglinte Gregory A. , Vasudevan Anupama , Rui Anna , Gart Mike , Pham Hoa , Aton Lindsay , Wang Brandon , Choksi Rushir J.
Published: June 2024

e19020

Background: BTKi therapies are standard of care for CLL/SLL, with acalabrutinib (acala) and zanubrutinib (zanu) having improved safety profiles vs ibrutinib (ibru). This study assessed real-world clinical characteristics, treatment patterns, and adverse events (AEs) among BTKi-treated patients with CLL/SLL. Methods: This is a retrospective observational study, updated with 5 months of additional data from a previous analysis. Adults in the US community oncology setting initiated BTKi treatment between Jan 1, 2020, and Jul 31, 2023, and were followed to Oct 31, 2023. De-identified structured electronic health records were analyzed from the Integra Connect-PrecisionQ real-world database. Cardiovascular (CV) AEs (based on ICD codes), time to treatment discontinuation (TTD), and time to next treatment (TTNT) were reported. Results: A total of 3064 patients initiated BTKi therapies during the index period (1L n=2815; 2L+ n=249). Median age (range) was 72 years (33-90) in 1L and 72 years (42-89) in 2L+. There were 63.1% and 65.5% males in 1L and 2L+, respectively. In 1L, 49.3% of patients were treated with ibru, 43.4% with acala, and 7.2% with zanu. Similar trends were observed for 2L+. More patients experienced CV AEs among those who received 1L ibru vs acala or zanu; 12.1%, 7.6%, and 7.3% at month 6 ( P<0.05) and 14.6%, 9.4%, and 8.5% at month 9 ( P<0.05). With longer follow-up, there was a trend for a more favorable CV safety profile for zanu. Of patients treated with 1L ibru, 12.7% discontinued ibru and switched to acala or zanu. Median TTD in 1L was shorter for ibru than acala or zanu (Table). The associated probability of remaining on treatment was higher with zanu vs ibru or acala at months 6 and 12 (Table). Median TTNT was not reached for zanu, while it was 30.2 months for ibru and 35.8 months for acala. Conclusions: While zanu had relatively smaller sample size and shorter follow-up, this study demonstrated better real-world safety and efficacy outcomes for acala and zanu vs ibru. Additional research is needed to explain and validate observed differences favoring zanu over acala. [Table: see text]
Clinical characteristics and independent prognostic factors of patients with mantle cell lymphoma over last two decades with a focus on the interaction between tumor stage and age.
Authors: Dey Shraboni , Fwelo Pierre , Nagesh Vignesh , Aguilar Izage Kianifar , Tran Hadrian , Wadhwani Nikita , Siddiqui Aman , Elias Daniel , Mansour Charlene , Gonzalez Marco , Harrison Jevon Lamar , Shoewu Oluwasegun , Weissman Simcha , Bangolo Ayrton
Published: June 2024

e19065

Background: Mantle Cell Lymphoma (MCL) poses challenges in clinical management due to its rarity and aggressiveness. Understanding its epidemiology and outcomes is crucial. This study examines demographic and clinicopathologic profiles of 746 MCL patients in the USA from 2000-2015, focusing on the interplay between age and tumor stage. Methods: Using SEER data, this retrospective study analyzes demographic and clinical variables to assess mortality risks. Univariate and multivariate Cox regression models evaluate overall mortality (OM) and MCL-specific mortality (CSM), identifying independent prognostic factors (HR >1). The study explores age-tumor stage interaction. Results: Multivariate Cox proportional hazard regression analysis revealed age as pivotal, with those ≥80 facing higher risks for overall mortality (HR=3.93) and MCL-related mortality (HR=4.02) . Advanced Ann Arbor staging (II, III, IV) predicts heightened risks for both mortality types. Widowed status significantly influences outcomes ,with widowed individuals facing notably higher risks of overall mortality (HR=1.85) and MCL-related mortality (HR=1.81).Stage II and age groups 60-79 and ≥80 show substantial mortality risks, with similar trends in Stage IV combined with these age groups. Intriguingly, Stage III lacks significant age interactions, suggesting heterogeneous clinical profiles and treatment responses compared to patients in Stages II and IV. Therefore, the influence of age on mortality outcomes may be obscured by the complexities inherent in Stage III disease presentation and management. Conclusions: This study underscores age, staging, and marital status as key factors influencing MCL mortality. Widowed status emerges as notable, emphasizing social support's importance. Integrating these insights into clinical practice can enhance risk stratification and guide tailored interventions for improved outcomes. Our findings, particularly the lack of significant interactions between Stage III and age groups, highlight the intricate interplay between age and disease stage in MCL patients. This observation prompts us to advocate for further research aimed at elucidating the underlying mechanisms driving these complex interactions. Understanding the biological and clinical factors that influence the relationship between age and disease stage could provide valuable insights into MCL pathogenesis and progression. Further research in this area is warranted to inform personalized therapeutic approaches and ultimately enhance patient care and outcomes.
Second line immune targeted therapies in relapsed or refractory diffuse large B-cell lymphoma: A network meta-analysis.
Authors: Syed Mohamed Aneesha Fathima , Kandikatla Renuka , Yakkala Vinod Kumar , Solodokin Loriel , Doucette Joanne , Yunusa Ismaeel , Eguale Tewodros
Published: June 2024

e19071

Background: Relapsed or refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) patients undergo multiple lines of burdensome therapies. We conducted a network meta-analysis (NMA) of phase 3 randomized control trials (RCTs) to evaluate the effectiveness of second-line (2L) immune targeted treatments (ITTs), including chimeric antigen receptor (CAR)-T cell therapies in R/R DLBCL patients, focusing on overall survival (OS), event-free survival (EFS), progression-free survival (PFS), overall response rate (ORR) and complete response (CR). Methods: In a systematic review, we searched RCTs from PubMed, Embase and Cochrane Library spanning January 2016 to September 2023.We included studies reporting on adults (≥18 years) DLBCL patients experiencing R/R to first-line anti-CD20 antibody and anthracycline-containing regimen. RCTs comparing ITTs with SOC (2L salvage chemoimmunotherapy regimens followed by stem cell transplantation) were included. Frequentist fixed-effect model was utilized to estimate hazard ratios (HRs) for survival outcomes and odds ratios (ORs) for binary outcomes (ORR and CR) with corresponding 95% confidence intervals (CIs). We ranked treatment effectiveness based on the surface under the cumulative ranking curves (SUCRA). Results: Our search identified 539 records; four RCTs contributed to the NMA: three comparing CAR-Ts, axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel), tisagenlecleucel (tisa-cel) with SOC, and one comparing ofatumumab + cisplatin, cytarabine, dexamethasone (O-DHAP) with SOC. Axi-cel significantly improved OS compared to both tisa-cel (HR, 0.59; 95% CI, 0.36-0.96) and SOC (HR, 0.73; 95% CI, 0.55-0.98). For EFS, axi-cel (HR, 0.38; 95% CI, 0.27-0.53) and liso-cel (HR, 0.32; 95% CI, 0.21-0.51) showed significant improvement compared to ODHAP. Axi-cel and liso-cel improved EFS significantly when individually compared to tisa-cel, and SOC.Axi-cel (HR, 0.51; 95% CI, 0.39-0.67) and liso-cel (HR, 0.4; 95% CI, 0.26-0.61) improved PFS significantly when compared to SOC. Axi-cel and liso-cel also significantly improved PFS when individually compared to ODHAP. In terms of ORR, Axi-cel (OR, 5.93; 95% CI, 3.63- 9.68) and Liso-cel (OR, 6.96; 95% CI, 3.37- 14.37) produced significantly higher ORR compared to SOC. Axi-cel and liso-cel had higher CR significantly when individually compared to ODHAP, tisa-cel, and SOC.In the SUCRA rankings, axi-cel was the most effective for OS, liso-cel ranked the most effective for EFS and PFS. Conclusions: Axi-cel was consistently associated with improved OS and EFS when compared to tisa-cel and SOC while liso-cel improved EFS and PFS over ODHAP and SOC. ORR and CR were higher for axi-cel and liso-cel over tisa-cel, ODHAP and SOC. Results are constrained by lack of multiple studies for each treatment comparison.
Survival outcomes in primary orbital diffuse large B-cell lymphoma.
Authors: Baidoun Firas , Hoppe Bradford S. , Tun Han W. , Alhaj Moustafa Muhamad
Published: June 2024

e19075

Background: Orbital diffuse large B-cell lymphoma is a rare entity accounts for less than 1% of all non-Hodgkin lymphoma cases. Large-scale studies describing and evaluating the effect of different type of treatments on survival outcome are lacking. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with primary orbital DLBCL between 2004 and 2020. All patients aged ≥ 18 years diagnosed with primary orbital DLBLC were included. We excluded patients with unknown chemotherapy and radiation therapy status or lost to follow-up (unknown vital status of last contact). Kaplan-Meier and multivariate Cox regression were used in the analyses. Results: The total cohort consisted of 404 patients with primary orbital DLBCL. Out of whom 233 (58%) were females, 326 (81%) were White non-Hispanic, 29 (7%) were White Hispanic and 16 (4%) were African Americans. 113 (28%) received chemotherapy only, 76 (19%) received radiation only, 113 (28%) received chemoradiation, 79 (20%) did not receive any treatment and 23 (6%) had unknown treatment status. The median age at diagnosis was 71 years (range 28-90). The median follow-up time was 132 months (95%CI 117-147), the median overall survival (mOS) for the whole cohort was 110 months (95%CI 82-138). Among patients with known treatment status and vital status of last contact (N=381), patient who received chemoradiation had significantly better mOS compared to patients who received radiation only (169 vs 67 months, P=0.002), but there was no statistically significant difference in mOS between chemoradiation and chemotherapy only (169 vs 124 months, P=0.068) or between chemotherapy only and radiation only (124 vs 67 months, P=0.213). On multivariate analysis, older age and Charlson-Deyo score of 2 were associated with worse OS (HR 1.072 95%CI 1.055-1.089; P<0.001, HR 2.292 95%CI 1.099-4.778; P=0.027, respectively). Compared to no treatment, only chemoradiation was associated with better OS (HR 0.509 95%CI 0.332-0.778; P=0.002), whereas chemotherapy only and radiation only did not add a survival benefit (HR 0.909 95%CI 0.598-1.381; P=656 and HR 0.766 95%CI 0.496-1.185; P=0.231). Conclusions: This large real-world analysis shows a survival benefit with combined treatment of chemoradiation in primary orbital DLBCL compared to single treatment modality.
Impact of hyponatremia on multiple myeloma hospitalizations: A nationwide analysis.
Authors: Jayakumar Jayalekshmi , Ginjupalli Manasa , Gaddam Mrunanjali , Vachhani Bhavyakumar , Iqbal Rabia , Stein Daniel , Hotwani Priya , Sanghvi Ankushi , Nanavaty Dhairya , Kumar Vikash , Sinha Rishav , Singh Surbhi , Clement Jincy
Published: June 2024

e19529

Background: Pseudohyponatremia has been studied to be a common laboratory artifact associated with Multiple Myeloma[MM] due to the paraproteinemia and the fluid shift. But recent studies are emerging with evidence of true hyponatremia in patients with MM usually associated with reduced anion gap. Hyponatremia is also one of the adverse effects with chemotherapy and major comorbidity associated with MM. In this study, we tried to study the effect of hyponatremia on the outcomes of MM. Methods: A retrospective analysis was formulated using the National Inpatient Sample database from 2016-2020. ICD 10 codes were used to find correlation between MM and Hyponatremia. The effects on morbidity, mortality, and secondary outcomes were compared in MM patients with Hyponatremia and without Hyponatremia. Categorical variables were compared using chi-square test, and continuous variables were compared using t-test. Multivariable regression analyses were performed adjusting for demographics, hospital-level characteristics, and relevant comorbidities. These included: Age, gender, race, Charlson Comorbidity Index, chronic kidney disease, congestive heart failure, adrenal insufficiency, polydipsia, hypothyroidism, alcohol use disorder, and various patient and hospital characteristics. Results: A total of 576,869 adults with MM were identified, of which 13.3% were diagnosed with hyponatremia. Mean age was 69 years, and 44 % were females. Patients with hyponatremia had 7.2% in-hospital mortality compared to 4.6% for patients without hyponatremia with an OR 1.61 [p-value 0.00]. Multivariate regression analysis showed that among those with MM, presence of hyponatremia increased the chance of mortality with OR 1.54 [1.43 - 1.65, p- value 0.00]. Hyponatremia also had significant impact on secondary outcomes including cerebral edema with OR 2.28 [1.76 - 2.95, p - value 0.00], AKI with OR 2.02 [1.94 - 2.09, p-value 0.00], Need for ventilator 2.28 [1.76 - 2.95, p-value 0.00] and sepsis 1.74 [1.66-1.81, p-value 0.00]. However there was no statistically significant differences found in venous thromboembolism and altered mental status. Hyponatremia also had an increased length of stay and Total hospital source utilization (Table). Conclusions: Hyponatremia is associated with multiple complications in MM hospitalizations. They even tend to portend worse prognosis as per our results. Further prospective studies are required to prove this association and management strategies should be established to improve outcomes and prevent complications. [Table: see text]
Prognostic factors for progression of MGUS including immune phenotype.
Authors: Bawek Sawyer , Joseph Janine , Hutson Alan , Parker Sarah , Tario Joseph , Hillengass Jens
Published: June 2024

e19537

Background: Monoclonal Gammopathy of Undetermined Significance (MGUS) is a benign precursor of multiple myeloma (MM). Individuals with MGUS have an overall 1% risk per year of disease progression to active MM or other cancers, although risk varies depending on multiple factors. Natural killer (NK) cells, cytotoxic CD8+ T cells, and dendritic cells have been shown to be altered in MM. Immune profile analysis can help to understand the microenvironment for monoclonal plasma cells better and help identify early factors for progression of MGUS into MM. Methods: We conducted a retrospective review of individuals from 2007-2023 who had a confirmed MGUS diagnosis and available flow-cytometry based immunophenotyping of peripheral blood. Demographics, Charlson Comorbidity Index (CCI), immunoglobulin subtype, date of diagnosis and progression, CD4/CD8 T-cell ratio, CD19+ B-cells, memory B-cells, gamma delta T cells, NK cells, and exhausted/non-exhausted CD4+ and CD8+ T cells were characterized. Descriptive statistics were expressed as means and standard deviations for continuous variables and tabulated frequencies for categorical variables. Pearson’s chi-square test of independence was used to explore the relationship between categorical race and diagnosis across categorical variables. Analysis of variance was utilized to assess the variation in continuous variables by race and diagnosis. The investigation of overall survival (OS) and progression-free survival (PFS) involved using univariate and multivariate Cox models across all pertinent variables. Hazard ratios (HRs) were estimated. A stepwise regression model was incorporated into the Cox multivariate model for a comprehensive analysis. All statistical tests were tested at alpha=0.05. Results: This retrospective study analyzed 151 patients, 84 (55.6%) being male. Average age was 55-77.8 years. The primary sub-diagnosis included IgG kappa at 30.5%, followed by IgG lambda at 29.8%. No significant associations were observed between MGUS subtype and comorbidities, race and Immunoglobulin subtype, Mayo risk status, and free light chain ratio (FLCR). After median follow-up of 666 days, median PFS was 8.07 years with a 95% CI of (4.45, 14.68), and median OS exceeded 12.71 years. The Univariate model for PFS identified the CCI Score (p=0.003, HR=1.25), FLCR (p=0.012, HR=1.024), and NK T-cells (%gated) (p=0.0211, HR=1.033) as significant factors. Only the CCI score was retained in the multivariate stepwise model. Univariate model for OS revealed associations with CCI (p<0.001, HR=1.50), NK T-cells (%gated) (p=0.007, HR=1.05), monoclonal protein (p=0.008, HR=2.80), Non-exhausted T-cells-CD4 (% of CD4+) (p=0.013, HR=0.96), and age (p=0.023, HR=1.09). Conclusions: In this single-center retrospective review, only CCI remained prognostically significant in the multivariate model. CCI and NK T-cells were prognostically significant for OS in the univariate analysis.
Phase 3 trial evaluating the efficacy and safety of odronextamab versus investigator’s choice in previously untreated follicular lymphoma (OLYMPIA-1).
Authors: Birhiray Ruemu Ejedafeta , Luminari Stefano , Kim Tae Min , Yağcı Münci , Wassenaar Timothy Robert , Risal Ashish , Namuduri Manjusha , Cai Jingxian , Fearon-Chalet Bertha , Zhu Min , Mukherjee Sushmita , Brouwer-Visser Jurriaan , Chaudhry Aafia , Mohamed Hesham , Ambati Srikanth R , Vitolo Umberto
Published: June 2024

TPS7096

Background: Follicular lymphoma (FL) is an incurable disease in which patients will relapse despite the effectiveness of first-line (1L) rituximab-based chemoimmunotherapy (CIT), indicating the need for alternative 1L treatments that can deepen and prolong response. Odronextamab, an off-the-shelf, CD20×CD3 bispecific antibody, showed compelling efficacy and generally manageable safety as a monotherapy at 3L+ for patients with relapsed/refractory (R/R) FL in the Phase 2 ELM-2 study (Villasboas, et al. ASH 2023). Objective and complete response (CR) rates were 80% and 73%, respectively, median duration of response was 22.6 months, median progression-free survival (PFS) was 20.7 months, and median overall survival was not reached. The rate of treatment-related adverse events leading to treatment discontinuation was 7.8%. The activity of odronextamab monotherapy in this heavily pretreated R/R FL population, including among patients with rituximab-refractory disease, provides a strong rationale for developing odronextamab as a chemotherapy-free option that can improve long-term outcomes in 1L. Methods: OLYMPIA-1 (NCT06091254) is a Phase 3, randomized, open-label, multicenter study of odronextamab versus investigator’s choice of CIT (R-CHOP, R-CVP, or R-bendamustine) in patients with previously untreated FL. The study consists of Part 1 (safety run-in), followed by Part 2 (randomization). In Part 1, patients will receive six 21-day cycles (induction) of intravenous odronextamab, administered in a step-up regimen during Cycle (C) 1 to mitigate the risk of cytokine release syndrome, followed by full dose starting from C2. Patients with CR or partial response at the end of induction will receive 12 doses of odronextamab maintenance given Q8W. In Part 2, patients will be randomized 1:1 to receive induction of six cycles of odronextamab followed by odronextamab maintenance, or CIT followed by rituximab maintenance. Key inclusion criteria: aged ≥18 years; CD20+ FL Grade 1–3a, stage II bulky or stage III/IV; measurable disease; and ECOG performance status 0–2. Patients with central nervous system lymphoma or histological Grade 3b are excluded. The Part 2 primary endpoint is CR at 30 months (CR30) as assessed by independent central review. Key secondary endpoints include PFS, event-free survival, investigator-assessed CR30, and patient-reported outcomes. Biomarkers (including minimal residual disease by ctDNA) will be evaluated as exploratory endpoints. This trial is currently recruiting and is expected to enroll ~12–32 patients in Part 1 and ~446 patients in Part 2 at ~200 global sites. Clinical trial information: NCT06091254 .
A phase III, randomized study of daratumumab, cyclophosphamide, bortezomib and dexamethasone (DARA-VCD) induction followed by autologous stem cell transplant or DARA-VCD consolidation and daratumumab maintenance in patients with newly diagnosed AL amyloidosis.
Authors: Hagen Patrick , Sidana Surbhi , Parker Terri L. , Walker Brian Keith , Hoering Antje , Sanchorawala Vaishali , Zonder Jeffrey A. , Kourelis Taxiarchis , D'Souza Anita , Landau Heather Jolie , Rosenthal Adam , Ailawadhi Sikander , Orlowski Robert Z
Published: June 2024

TPS7575

Background: Light chain (AL) amyloidosis is a plasma cell malignancy characterized by the production of amyloidgenic clonal light chains that deposit in various tissues. The addition of daratumumab to bortezomib, cyclophosphamide and dexamethasone (Dara-VCD) has improved depth of hematologic and organ responses. However, this approach has not yet demonstrated an overall survival (OS) benefit with short follow-up. Autologous stem cell transplant (ASCT) consolidation remains safe and is associated with deep and durable hematologic responses with an 83% 2-year progression free survival (PFS) and up to 72% of patients achieving a VGPR or better, comparable to Dara-VCD (79%). In multiple myeloma, ASCT improved PFS even in patients who are MRD negative at the end of standard induction therapy. It is thus reasonable to consider that ASCT might provide similar benefits in AL patients. No randomized data exist to inform the optimal use of ASCT in the era of Dara-VCD. Methods: This randomized phase 3 SWOG led intergroup trial will accrue a total of 143 participants per arm and compare MOD-PFS (major organ deterioration progression free survival: defined as time from randomization to death, cardiac/renal progression, or hematologic progression) between participants receiving an ASCT with those receiving Dara-VCD consolidation following uniform Dara-VCD induction. A median MOD-PFS of 31 months is anticipated in the non-ASCT arm. This study has 90% power and a two-sided significance level of 0.05 to detect a hazard ratio of 0.62 corresponding to a MOD-PFS of 50 months in the ASCT arm. Important additional endpoints include OS, hematological PFS, cardiac and renal responses and progression, MRD negativity both by peripheral blood mass spectrometry and bone marrow next generation flow cytometry, delayed utilization of ASCT, and quality of life. This trial was activated on 12/1/2023. Funding: NIH/NCI/NCTN grants and in part by Janssen Pharmaceuticals. Clinical trial information: NCT06022939 . [Table: see text]
Self-Trephination in Cranial Excoriation Disorder
Authors: Riordan Coleman P. , Owusu-Adjei Brittany , Daci Rrita , Phelan Alannah , Mietus Constance J. , Kosarchuk Jacob , Lambert William , Qureshi Hanya M. , Lim Jeewoo Chelsea , Mihalek Olivia , Li Danielle , Sorour Omar , Homsy Christopher , Kryzanski James , Aulet Ricardo , Johnson Mark D.
Published: June 2024

BACKGROUND AND IMPORTANCE:

Trephination is a procedure in which a small hole is made in the skull. Rare cases of self-trephination by individuals seeking medical benefit have been reported. Excoriation disorder is a compulsive skin-picking condition in which an individual self-inflicts cutaneous lesions. Left untreated, severe excoriation disorder can pose significant health risks.

CLINICAL PRESENTATION:

Here, we describe 5 patients who presented with self-trephination due to a severe form of compulsive cranial excoriation at 2 neighboring academic medical centers over a 4-year period. We review the clinical presentation of self-trephination in cranial excoriation disorder and associated risk factors, surgical and nonsurgical interventions, complications of the disease, treatments, and mortality. Defining clinical characteristics include repetitive self-induced destruction of the scalp and skull with entry into the intracranial compartment, frequent psychiatric comorbidities, infection or injury of the brain with consequent neurological morbidity or mortality, and frequent treatment failures because of poor adherence.

CONCLUSION:

Self-trephination in cranial excoriation disorder is a severe neuropsychological disorder and neurosurgical emergency that exposes the brain and is often life-threatening. Appropriate therapy requires antibiotics, surgical debridement and repair of the wound, and concomitant effective psychiatric management of the underlying compulsion, including the use of antidepressants and behavioral therapy.
Σύγχρονες μέθοδοι λήψης αποφάσεων για την ορθολογική κατανομή των δημοσίων και ιδιωτικών πόρων
Authors: Πετρόπουλος Θεοφάνης
Published: June 2024

Η εξέλιξη της διαδικασίας λήψης αποφάσεων τα τελευταία χρόνια έχει ραγδαία ανάπτυξη συνεργατικά με τις μεθόδους επίλυσης προβλημάτων της επιχειρησιακής έρευνας, προσπαθώντας να βοηθήσουν στην ποιοτική λήψη αποφάσεων από τα στελέχη επιχειρήσεων και οργανισμών, με σκοπό την ορθολογική κατανομή των περιορισμένων πόρων τόσο στον ιδιωτικό όσο και στο δημόσιο τομέα αξιοποιώντας παράλληλα τη διαθέσιμη χρηματοοικονομική πληροφορία που έχει καταγραφεί. Στην Ελλάδα κυρίως στο Δημόσιο αλλά ως ένα βαθμό και στον ιδιωτικό τομέα, δεν έχουν αναπτυχθεί επαρκείς εφαρμογές για την επίλυση προβλημάτων που αντιμετωπίζονται συνεχώς όσον αφορά την ορθή κατανομή και αξιοποίηση των πόρων. Αυτό συμβαίνει λόγω μεγάλου χρόνου που χρειάζεται τις περισσότερες φορές για τον υπολογισμό των μεθόδων με σκοπό την εξαγωγή ορθολογικών αποφάσεων εξαιτίας των συνεχών αλλαγών και της αβεβαιότητας που επικρατεί στην πραγματική ζωή (ελληνική οικονομική και επιχειρηματική πραγματικότητα), για αυτό το λόγο οι επιχειρήσεις στηρίζονται κυρίως στην εμπειρία των καταρτισμένων στελεχών που διαθέτουν. Ξεχωριστά έχουν αναπτυχθεί διάφορες θεωρίες που βοηθούν στην διαδικασία λήψης αποφάσεων βασιζόμενες σε παραδοσιακές κυρίως μεθοδολογίες που έχουν δημιουργηθεί, ένας συνδυασμός όμως δύο ή περισσότερων για την επίλυση ενός προβλήματος θα μπορούσε να δώσει μια καλύτερη απάντηση στα ερωτήματα που προκύπτουν. Η παρούσα ερευνητική πρόταση αποσκοπεί κυρίως στην ανάπτυξη ειδικών τρόπων επίλυσης εφαρμογών όπως πχ. πρόβλημα σακιδίου οι οποίοι θα είναι πιο αποδοτικοί από τις παραδοσιακές μεθόδους όπως πχ. simplex (Dantzig, 1963) πάνω σε πρωτότυπα προβλήματα της οικονομικής δραστηριότητας της ελληνικής οικονομίας. Συνδυάζοντας διάφορες είδη γνωστές μεθόδους μαθηματικής μοντελοποίησης πχ. γραμμικός, δυναμικός προγραμματισμός (Bellman, 1957; Dantzig, 1963), και νέων ευρετικών και μεταευρετικών μεθόδων όπως οι γενετικοί αλγόριθμοι Holland, (1975) η στόχευση είναι στη δημιουργία υβριδικών μοντέλων τα οποία θα είναι πιο αποτελεσματικά καλύπτοντας και τον απαιτούμενο βαθμό αβεβαιότητας. Επίσης η αξιοποίηση της καταγραφής της χρηματοοικονομικής πληροφορίας και η αξιοποίηση των πηγών – χρήσεων κεφαλαίου έτσι ώστε να μπορούν να εφαρμοστούν σύγχρονοι μέθοδοι λήψης αποφάσεων. Η έρευνα αναμένεται να βοηθήσει τόσο τους ερευνητές όσο και τους επαγγελματίες στη λήψη αποφάσεων για την αποτελεσματικότερη διαχείριση του προϋπολογισμού και την ορθολογική κατανομή των περιορισμένων – διαθέσιμων πόρων.