bluuebunny/crossref_metadata_2025_split huggingface dataset:
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]