bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extended follow-up results beyond 2.5 years from the pivotal NHL-1 EPCORE trial: Subcutaneous epcoritamab monotherapy in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL).
Authors: Karimi Yasmin , Thieblemont Catherine , Ghesquieres Hervé , Cheah Chan Y , Clausen Michael Roost , Cunningham David , Jurczak Wojciech , Linton Kim M. , Hutchings Martin , Phillips Tycel Jovelle , Farooq Umar , Kim Won Seog , Dinh Minh H , Ghosh Jagannath , Pallai Rajash , Wielgos-Bonvallet Monica , Eskelund Christian , Lugtenburg Pieternella , Vose Julie 
Published: June 2024

7039 Background: Epcoritamab induces high complete response (CR) and MRD-negativity rates with manageable safety in patients (pts) with challenging-to-treat R/R LBCL as shown in the pivotal phase 2 study (NCT03625037). Here we present long-term data, an additional efficacy analysis from the expansion cohort, and data from the cycle 1 optimization (C1 OPT) part. Methods: Adults with R/R CD20+ LBCL and ≥2 prior systemic therapies received subcutaneous epcoritamab (2 step-up doses, then 48-mg full doses per label) in 28-d Cs. The primary endpoint of the expansion cohort was IRC-assessed overall response rate (ORR). A subgroup analysis evaluated efficacy outcomes by investigator assessment in complete responders with longer follow-up. C1 OPT assessed CRS incidence and severity with hydration and dexamethasone prophylaxis in C1; hospitalization was not required. Results: Overall, 157 LBCL pts were treated in the expansion cohort; 148 had diffuse LBCL (DLBCL) or high-grade B-cell lymphoma (HGBCL). Baseline characteristics were previously reported. As of April 21, 2023, the median follow-up for LBCL was 25.1 mo (range, 0.3+ to 32.7); ORR/CR rates were 63/40% (LBCL) and 61/39% (DLBCL + HGBCL) by IRC. In a subgroup analysis of complete responders with longer follow-up (median, 31.3 mo), median duration of CR was not reached; efficacy outcomes for complete responders are shown in the Table. Long-term safety was consistent with previous reports. CRS remained the most common AE (51% all grade [G]; 32% G1, 16% G2, 3% G3). In C1 OPT, 36 pts were evaluable for CRS with a median follow-up of 1.7 mo. Overall CRS incidence was 22% and events were low grade (14% G1, 8% G2), mostly occurring following the first full dose. All CRS events resolved; none led to treatment discontinuation. Among 60 total pts in C1 OPT, 1 pt experienced ICANS (G1). Additionally, IL-6 levels were lower with C1 OPT and consistent with the observed lower rate and severity of CRS. Preliminary C1 OPT efficacy data were comparable to data observed in the expansion cohort. Conclusions: Epcoritamab monotherapy continues to demonstrate deep and durable responses, with most complete responders remaining in CR and without new safety signals in these long-term follow-up analyses. Implementing simple measures of adequate hydration and prophylactic dexamethasone in C1 markedly reduced the overall incidence and severity of CRS with no impact on efficacy. The continued benefit beyond 2.5 y underlines the long-term efficacy and value of epcoritamab in R/R LBCL. Clinical trial information: NCT03625037 . [Table: see text]
Real-world risk of bleeding events in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) treated with BTKi.
Authors: Moslehi Javid J. , Wahlstrom Svea K , Teschemaker Anna , Mackey Rachel H , DeVincenzo Diana , Carabuena Leslie A , Thompson Samantha L , Gordon Brittaney , Rosenthal Ning A 
Published: June 2024

7052 Background: Bruton tyrosine kinase inhibitors (BTKis) are effective treatments for various B-cell malignancies including CLL/SLL but are known to be associated with increased bleeding risk. Current evidence indicating this association has largely been demonstrated in clinical trial research. However, bleeding risk in real-world CLL/SLL patients, who are often sicker with more comorbidities requiring anticoagulant (AC) or antiplatelet (AP) use is not well described. This study aimed to assess the prevalence of AC/AP use and explore risk factors for bleeding among real-world CLL/SLL patients receiving BTKi therapies. Methods: We conducted a retrospective cohort study using the claims-linked Premier PINC AI Healthcare Database of patients aged ≥18 years with a diagnosis of CLL/SLL from July 1, 2016 to March 31, 2022. Patients were followed from first BTKi prescription fill (index date) to earliest of BTKi discontinuation, death, or end of the study period. Patient comorbidities, treatments, and bleeding events were assessed using diagnosis and procedure codes and prescription claims. Multivariable-adjusted risk for bleeding events was assessed with Cox proportional-hazards regression. Results: Among 2091 patients with CLL/SLL receiving BTKi therapies, mean age was 65.7 years, 61.8% were men, and 77.7% were White. BTKi treatments included ibrutinib (86.3%), acalabrutinib (13.1%), and zanubrutinib (<1%). Overall, 4.3% of patients switched BTKis during follow-up; 615 (29.4%) had AC/AP use at any time during the study period, of whom 411 (66.8%) started after BTKi initiation. Bleeding events occurred in 526 (25.2%) patients during a mean BTKi exposure of 14.2 months, with an incidence of 26.6 per 100 person-years (PYs) overall, and 37.2 and 22.0 per 100 PYs in patients with and without any prescription AC/AP use, respectively. The proportion of patients with fatal bleeding was <0.3%. In adjusted models, risk of first bleeding event was higher for AC use (HR [95% CI] 2.33 [1.83–2.98]), age ≥65 years (1.32 [1.14–1.53]), women (1.28 [1.10–1.48]), and history (during 90 days prior to BTKi start) of bleeding (2.27 [1.87–2.76]), ulcers (2.21 [1.06–4.63]) or myocardial infarction (MI) (1.74 [1.31–2.33]) (all P≤0.05). Prescription AP use, race/ethnicity, and history of chronic kidney disease or thrombocytopenia were not statistically significant. Conclusions: In this large real-world study of bleeding risk in patients receiving BTKis, bleeding events occurred in 26.6 per 100 patients per year, with higher risk in AC users, women, and patients with history of bleeding, ulcers, or MI. However, the risk of fatal bleeding was low.
Frontline brentuximab vedotin and CHP (A+CHP) in patients (pts) with peripheral T-cell lymphoma with less than 10% CD30 expression: Results from the phase 2 SGN35-032 study.
Authors: Iyer Swaminathan Padmanabhan , Jagadeesh Deepa , Domingo-Domenech Eva , Benedetti Fabio , Rodriguez Izquierdo Antonia , Bouabdallah Krimo , Vitolo Umberto , Illidge Tim M. , Liu Jingmin , Shaikh Eeman , Horwitz Steven M. 
Published: June 2024

7069 Background: Brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, combined with cyclophosphamide, doxorubicin, and prednisone (A+CHP) was evaluated in the phase 3 ECHELON-2 trial in pts with anaplastic large cell lymphoma (ALCL) and other peripheral T-cell lymphoma (PTCL) types with ≥10% CD30 expression. Compared to conventional frontline therapy, pts treated with A+CHP had a 30% risk reduction in progression-free survival (PFS) (stratified HR=0.70 [95% CI: 0.53, 0.91], P=0.0077) and a survival benefit (HR=0.72 [95% CI: 0.53, 0.99], P=0.0424) (Horwitz 2022). Since no correlation between CD30 expression and duration of response (DOR) was found, it was hypothesized that frontline A+CHP may also be active in pts with non-sALCL PTCL with <10% CD30 expression. Methods: SGN35-032 (NCT04569032; EudraCT 2020-002336-74) is an ongoing phase 2 study. Pts with newly diagnosed non-sALCL PTCL with <10% CD30 expression (by local assessment) are enrolled. Pts are assigned to CD30 <1% or CD30 1% to <10% cohorts. All pts receive 21-day cycles of A+CHP (BV 1.8 mg/kg, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2 by IV infusion, and prednisone 100 mg po qd on Days 1-5) for up to 6-8 cycles. The primary endpoint, overall response rate (ORR), is assessed by blinded independent central review (BICR) per Cheson 2007. Secondary endpoints are complete response (CR) rate, PFS, overall survival (OS), DOR, ORR per BICR using modified Lugano, and safety. Results: Seventy pts received ≥1 dose of study drug as of June 30, 2023. Median age was 63.5 years, 57% were male, and 90% had ECOG ≤1. Most had stage IV disease (63%) and were in the CD30 1% to <10% cohort per local CD30 (55%). Median treatment duration was 18 weeks (range, 0-24 weeks). Per BICR, ORR was 77% (95% CI: 65.3%, 86.7%), including 65% (95% CI: 52.4%, 76.5%) with CR among the 66 efficacy evaluable (EE) pts. ORR and CR rate per BICR are listed by cohort in the Table. Grade ≥3 treatment-emergent adverse events (TEAEs) were experienced by 43 pts (61%), most commonly neutropenia (20%), febrile neutropenia (17%), and anemia (10%). Six pts (9%) discontinued treatment due to TEAEs. Nineteen pts (27%) had BV-related serious TEAEs. There were 2 (3%) treatment-related deaths: 1 pt died of decreased appetite and 1 pt died of general physical health deterioration. Conclusions: In pts with non-sALCL PTCL with <10% CD30 expression, A+CHP as frontline therapy appears effective and has a safety profile consistent with label. Clinical trial information: NCT04569032 . [Table: see text]
Impact of renal impairment (RI) on pharmacokinetics (PK) and clinical outcomes with mezigdomide plus dexamethasone (DEX) in relapsed/refractory multiple myeloma (RRMM).
Authors: Trudel Suzanne , Bahlis Nizar J. , Popat Rakesh , Mateos Maria-Victoria , Vangsted Annette J. , Ramasamy Karthik , Martínez-Lopez Joaquín , Quach Hang , Orlowski Robert Z , Burnett Joseph , Gaudy Allison , Chen Wencong , Gong Jing , Hadala Joseph T. , Donahue Cynthia , Koo Phillip , Zhu Yue , Katz Jessica , Richardson Paul G. 
Published: June 2024

7539 Background: RI is a common complication in MM and may alter drug elimination, leading to increased systemic exposures, risk of adverse events (AEs), and dosing adjustments. The novel CELMoD agent mezigdomide (MEZI) is being investigated alone or with DEX in the CC-92480-MM-001 (NCT03374085) phase 1/2 trial. MEZI has shown dose-dependent linear PK with rapid absorption and is mainly eliminated through hepatic metabolism, with renal elimination playing a smaller role. Here we investigate the impact of RI on the efficacy, safety, and PK of MEZI + DEX in RRMM. Methods: Eligible patients (pts) had RRMM, ≥ 3 prior lines of therapy, triple-class refractoriness, and disease progression ≤ 60 days of last therapy. Pts were stratified by creatinine clearance (CrCl), excluding those with CrCl < 45 mL/min or needing dialysis. Oral MEZI (1 mg) was given on days 1–21 per 28-day cycle + weekly DEX. MEZI doses were not adjusted based on RI. Responses, AEs, and PK were assessed descriptively over the full population and in pts with no RI (CrCl ≥ 90 mL/min), mild RI (CrCl 60–< 90 mL/min), and moderate RI (CrCl 30–< 60 mL/min) at baseline. MEZI clearance and PK exposure were estimated from an integrated population PK model. PK exposure parameters were stratified by chronic kidney disease (CKD) staging. Results: 101 pts received MEZI + DEX in the dose-expansion cohort; 37 had no RI, 41 had mild RI, and 23 had moderate RI. Grade (Gr) 3/4 treatment-emergent AEs (TEAEs) were similar, occurring in 91.1% (overall), 89.2% (no RI), 90.2% (mild RI), and 95.7% (moderate RI) of pts. TEAEs were mostly hematologic, with neutropenia the most common Gr 3/4 TEAE; its occurrence did not differ in no RI (75.7%), mild RI (75.6%), and moderate RI (73.9%) cohorts. Non-hematologic Gr 3/4 TEAEs were low. Eighty-nine (88.1%) and 32 (31.7%) pts had MEZI dose interruptions and reductions, respectively. Overall response rate (ORR) was 40.6% in all pts, 56.8% in no-RI pts, 29.3% in mild-RI pts, and 34.8% in moderate-RI pts (Table). Evaluated as a continuous variable, CrCl showed no apparent relationship with MEZI oral clearance or systemic exposures. This was supported by subgroup evaluation of MEZI exposures by CKD stage. Results showed MEZI exposures in mild or moderate RI are consistent with no RI. Conclusions: Based on renal function, there was no adverse trend between efficacy, safety, and PK of MEZI + DEX. MEZI dose modifications are likely not required for pts with mild to moderate RI. Clinical trial information: NCT03374085 . [Table: see text]
Mortality trends (1999-2022) in patients with multiple myeloma with pneumonia, influenza, and COVID-19.
Authors: Zolotov Eli , Parmar Harsh , Anand Palka , Zenreich Josh , Aleman Adolfo , Phull Pooja , Vesole David H. , Siegel David Samuel DiCapua , Biran Noa 
Published: June 2024

7553 Background: Patients (pts) with multiple myeloma (MM) are immunosuppressed either due to the hypogammaglobulinemia and impaired plasma cell function or due to pharmacological management and stem cell transplantations. Consequently, they are at a higher risk of infections. This study aims to evaluate the changes in mortality from COVID-19 (CVD), influenza virus (FLU), and pneumonia (PNA) in MM pts in the era of CVD pandemic. Methods: Using the Wide-ranging Online Data for Epidemiologic Research (WONDER) database from the CDC, we collected mortality data for pts with CVD (U07.1 code), FLU and PNA (J09-J18 codes), and MM (C90.0 code). Using sex and ethnicity-specific stratification, the gathered data made it easier to calculate age-adjusted mortality rates (AAMRs) per 100,000 people. Using the collected data we were able to analyze mortality patterns over the years 1999-2022. Results: Overall, 25,271 MM pts died from CVD, FLU and PNA between 1999 to 2022. The mortality rate remained stable from 1999 to 2019 ranging between 0.4 AAMR per 100,000 to 0.3 AAMR, representing an annual percentage change (APC) of -0.5%. However, the mortality rate increased in 2019, rising from 0.3 AAMR per 100,000 to 0.5 in 2022, with APC of 7%. When evaluating the trends by gender, there was an increase in mortality among male pts, rising from 0.4 AAMR per 100,000 to 0.7 between 2019 and 2020, while the increase among females was minimal, from 0.3 AAMR per 100,000 to 0.4. While Hispanic, White, and African American ethnicities mortality increased in 2020-2022, Asian pts maintained a rate of 0.2 AAMR in 2019, 2020, and 2022 (Table). Conclusions: We showed an increase in mortality among pts with MM combined with CVD, FLU, or PNA between 2020 and 2021. It might be attributable to the CVD pandemic, announced by WHO in March 2020. Despite the FDA's approval of the first CVD vaccine in December 2020, the emergence of new CVD variants and limited vaccine availability could have contributed to a continued increase in mortality in 2021.In 2022, we noticed a drop in mortality. It might be explained by the wider accessibility to CVD vaccination or to diminished virulence. Additionally, increased awareness of the importance of CVD vaccinations in immunocompromised pts could also lead to increased FLU vaccination rates. It might explain the downtrending mortality of pts with MM, FLU and PNA only in 2021. This is the first study presenting the mortality trend of MM pts with FLU, PNA and CVD, and comes to highlight the importance of vaccination in immunocompromised MM pts. [Table: see text]
Smoking and pathogenic germline variants in patients with lung cancer.
Authors: Esplin Ed , Nielsen Young Sarah M. , Russell Emily M. , Ellsworth Rachel , Heald Brandie , Watson Alexander S , Aisner Dara L. , Korn W. Michael 
Published: June 2024

8040 Background: Few studies have investigated the correlation of smoking history with pathogenic germline variants (PGVs) in patients diagnosed with lung cancer. With emerging opportunities for PGVs in DNA damage-repair (DDR) genes to inform precision therapies, we investigated the prevalence of PGVs in patients with lung cancer, stratified by smoking status. Methods: Germline genetic testing (GGT) (Invitae Corp.) and insurance claims (Komodo Healthcare MapTM) data were reviewed for 14,317 patients with an ICD code for lung cancer from 2015-2023 and hereditary cancer GGT of ≥ 10 genes. PGV rates were assessed overall, in DDR genes and in lung cancer related genes. Smoking history was defined by ICD codes. Number of genes tested varied per ordering clinician preference. Clinically actionable PGVs were defined as those associated with clinical management recommendations or trial eligibility per current standard of care guidelines. Chi-square tests were used with significance set to p < 0.05. Results: The cohort was predominantly female (70.9%), white (65.7%), and over half had a history of smoking (57.1%). PGVs in 73 known cancer-risk genes were identified in 1,804/14,317 (12.6%) patients. Frequencies of PGV were 12.6% (1,026/8,175) in patients with smoking history compared to 12.7% (778/6,142) in those with no reported smoking history. There was no statistically significant difference in DDR gene, TP53, or EGFR PGV rates for patients with or without smoking history (p > 0.05). Mean (SD) age of lung cancer diagnosis was significantly younger for patients with a history of smoking and DDR PGVs (61 (11)) compared to those with negative results (62 (12), p = 0.005). There was no significant difference in age of diagnosis between patients with no smoking history and DDR PGVs (60 (12)) and those with negative results (59 (13), p = 0.888). PGV rates by clinician-reported ancestry: Black/African-American, 9%; Asian or Pacific Islander, 11%; Hispanic, 12%; White, 13%. Among genes with > 1,000 patients tested, PGVs were most common in BRCA2 (2.2%), CHEK2 (2.0%), ATM (1.6%), SPINK1 (1.6%), and BRCA1 (1.2%). Conclusions: In 14,317 patients with lung cancer, 12.6% had PGVs. There was no significant difference in enrichment of PGVs in DDR genes when patients were stratified by reported smoking history, suggesting the enrichment of these genes is independently associated with lung cancer. The age of onset for patients with DDR gene PGVs varied with smoking history, suggesting that risk conferred by these PGVs could be additive to smoking risk. These data reinforce prior studies supporting consideration of GGT for all patients with lung cancer, independent of age or reported smoking history.
Long-term survival, toxicities, and the role of chrono-chemotherapy with different infusion rates in patients with locally advanced nasopharyngeal carcinoma treated with intensity-modulated radiation therapy: A retrospective study with a 5-year follow-up.
Authors: Liu Lina , Luo Xunyan , Wu Weili , Li Yuanyuan , Long Jinhua , Luo Xiuling , Chen Xiaoxiao , Gong Xiuyun , Zhao Chaofen , LI Zhuoling , Shang Kai , Xu Xinyu , Jin Feng 
Published: June 2024

e18003 Background: This study aimed to evaluate 5-year outcomes and the late toxicity profile of chrono-chemotherapy with different infusion rates in patients with locally advanced nasopharyngeal carcinoma (NPC). Methods: Our retrospective analysis included 70 patients with locally advanced NPC stages III and IVB (according to the 2010 American Joint Committee on Cancer staging system). Patients were treated with two cycles of induction chemotherapy (IC) before concurrent chemoradiotherapy (CCRT) at the affiliated cancer hospital of Guizhou medical university. The IC with docetaxel, cisplatin (DDP) and fluorouracil regimen. Patients were divided into two groups during CCRT. Using a “MELODIE” multi-channel programmed pump, DDP (100 mg/m2) was administered for 12 hours from 10:00 am to 10:00 pm and repeated every 3 weeks for 2-3 cycles. DDP was administered at the peak period of 4:00 pm in the sinusoidal chrono-modulated infusion group (Arm A, n = 35). The patients in Arm B received a constant rate of infusion. Both arms received radiotherapy through the same technique and dose fraction. The long-term survival and disease progression were observed. Results: After a median follow-up of 82.8 months, the 5-year progression-free survival rate was 81.3% in Arm A and 79.6% in Arm B (P = 0.85). The 5-year overall survival rate was not significantly different between Arm A and Arm B (79.6% vs 85.3%, P = 0.79). The 5-year distant metastasis-free survival rate was 83.6% in Arm A and 84.6% in Arm B (P = 0.75). The 5-year local recurrence-free survival rate was 88.2% in Arm A and 85.3% in Arm B (P = 0.16). There were no late toxicities of grade 3-4 in either group. Both groups had grade 1-2 late toxicities. Dry mouth was the most common late toxic side effect, followed by hearing loss and difficulty in swallowing. There was no statistically significant difference between Arm A and Arm B in terms of side effects. Conclusions: Long-term analysis confirmed that in CCRT, cisplatin administration with sinusoidal chrono-modulated infusion was not superior to the constant infusion rate in terms of long-term toxicity and prognosis.
Screening failure in clinical trials for patients with head and neck squamous cell carcinoma: A retrospective analysis.
Authors: Jiménez Labaig Pablo , Llop Sandra , Rullan Antonio , O'Leary Ben , Newbold Kate , Wong Kee Howe , Bhide Shreerang , Nutting Christopher , Harrington Kevin Joseph 
Published: June 2024

e18009 Background: Clinical trials drive improvements in patient care with head and neck squamous cell carcinoma (HNSCC), presenting opportunities for optimizing clinical outcomes. However, a significant number of patients (pts) miss out on new therapeutic opportunities due to screen failure (SF) after signing the informed consent form. Understanding the circumstances leading to SF might improve enrollment processes. Methods: Retrospective cohort analysis of pts with HNSCC intended for treatment within a clinical trial at the Royal Marsden Cancer Centre but who experienced SF between Jan 2016 and Jan 2024. Demographic and cancer-related characteristics, comorbidities, consent and SF dates, SF causes, and subsequent outcomes after SF were analyzed. Results: 76 pts who experienced SF were identified across 33 different trials. Cohort characteristics and type of trials offered are described in the table. The largest number of SFs was due to exclusion criteria being met in screening tests in 37 pts (49%): Pathology sample did not meet the quality standards in 11 pts (14%); abnormal laboratory tests in 5pts (6%); abnormal echocardiogram/reduced ejection fraction in 5 pts (6%); vessel invasion/ encasement in 4 pts (5%); non-measurable disease in 2 pts (3%); abnormal audiometry in 1pt (1%) among other reasons. The next commonest cause of SF was rapid progression during screening in 28 pts (37%): 11% compromised airway; 11% active bleeding; 5% central nervous system progression and 7% other rapid progression causes. Other causes of SF included: withdrawn consent in 7 pts (9%), comorbidity-related complication in 3 pts (5%) and study termination by sponsor in 2 pts (3%). The median time between consenting and SF was 20 days (range 4-42). After SF, 8% reconsented for the same trial, 56% received standard therapy, and 36% received best supportive care. Conclusions: This study reveals abnormal screening tests and rapid progression as primary causes for SF in patients with HNSCC. Timely referral , airway assessments and improved tissue acquisition could improve enrollment and minimize SF. [Table: see text]