bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of patients with a myeloproliferative neoplasm and atrial fibrillation.
Authors: Leiva Orly , How Chi-Joan , Brunner Andrew , Grevet Jeremy , Hobbs Gabriela 
Published: June 2023

7070 Background: Patients with myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), are associated with increased risk of cardiovascular (CV) disease including arterial thrombosis (AT). Atrial fibrillation (AF) is also associated with increased risk of AT and often co-exists with MPN. However, thrombotic and bleeding outcomes in patients with MPN compared with those without have not been thoroughly investigated. Methods: Patients aged ≥ 18 years with a hospital admission for AF with and without a history of MPN in 2017 and 2018 were identified using the National Readmission Database. Primary outcomes were 30-day (D) and 90-D any-cause, AT-related (including stroke, myocardial infarction, arterial thromboembolism), and bleeding-related readmissions. Propensity score weighting (PSW) was performed in order to adjust for imbalances between MPN and non-MPN patients. PSW Cox proportional hazards was performed to estimate risk of 90-D readmission in patients with MPN compared with patients without. Results: A total of 468,094 patients with AF were identified with 1,617 patients having a history of MPN. CHA2DS2-VASC (mean 3.8 vs 3.7) and HAS-BLED scores (mean 2.4 vs 2.3), risk scores for AT and bleeding in AF, were similar between MPN and non-MPN patients. After PSW Cox proportional hazards, patients with MPN had an increased risk of 30-D all-cause (HR 1.72, 95% CI 1.70 – 1.74), AT (HR 1.45, 95% CI 1.38 – 1.53), and bleeding (HR 2.21, 95% CI 2.01 – 2.44) re-admissions. MPN patients had an increased risk of 90-day any cause (HR 1.38, 95% CI 1.37 – 1.40) and bleeding (HR 1.76, 95% CI 1.65 – 1.88) but not AT (HR 1.03, 95% CI 0.99 – 1.08) readmissions. Conclusions: Among patients admitted for AF, MPN is associated with increased risk of 30-D and 90-D any-cause and bleeding readmissions and 30-D AT readmissions despite similar CHA2DS2-VASC and HAS-BLED risk scores. Further studies are needed to identify risk factors for bleeding and AT in patients with MPN and AF and improve on current risk scores, which do not include MPN status. [Table: see text]
Outcomes of individuals with clonal hematopoiesis evaluated at a cancer center.
Authors: Chien Kelly Sharon , Ong Faustine , Kim Kunhwa , Li Ziyi , Kanagal-Shamanna Rashmi , Dinardo Courtney Denton , Takahashi Koichi , Montalban-Bravo Guillermo , Hammond Danielle , Sasaki Koji , Pierce Sherry , Kantarjian Hagop M. , Garcia-Manero Guillermo 
Published: June 2023

7072 Background: Clonal hematopoiesis (CH) refers to the presence of somatic mutations in individuals without overt hematological disorders. CH, including CH of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS), is associated with hematologic malignancies and other systemic comorbidities. There are currently no established guidelines regarding the optimal monitoring and management of patients with CH, and the impact of CH in patients with concomitant underlying malignancies remains unknown. Methods: Patients seen at a tertiary cancer center with at least 1 somatic mutation detected by next generation sequencing on bone marrow aspirate or peripheral blood between January 2015 and March 2021 were included. Patients with donor-derived CH or any morphologic evidence of a myeloid neoplasm were excluded. Results: We evaluated 78 patients – 76% had a history of malignancy and 73% had other comorbidities. The mutations most frequently observed were DNMT3A (40%), TET2 (31%), TP53 (26%), and ASXL1 (18%). The median overall survival for all patients was not reached (2-year survival rate of 79%). Most deaths were related to primary malignancies (35%), comorbidities (20%), or myeloid neoplasms (20%). Due to concomitant use of antineoplastic therapy and other causes of cytopenia in 19 patients, we further categorized patients into 4 groups: CHIP on treatment (CHIP-T), other CHIP (CHIP-O), CCUS on treatment or with a non-myeloid hematologic malignancy (CCUS-T), and other CCUS (CCUS-O). Transformation to a myeloid neoplasm occurred in 12 patients (15%). The 3-year cumulative incidence of transformation was higher in CCUS-O (24%) and CCUS-T (21%) compared to the CHIP group (6%, p = 0.48). On univariate analysis, increasing age, variant allele frequency (VAF) ≥ 0.2, hemoglobin < 10 g/dL, and any chromosomal abnormalities were associated with higher risk for transformation. By multivariate analysis, transformation was only significantly associated with VAF ≥ 0.2 (hazard ratio (HR) 18.25; 95% confidence interval (CI): 3.59, 92.73; p = 0.0005) and hemoglobin < 10 g/dL (HR 15.62; 95% CI: 3.29, 74.05; p = 0.0005). Conclusions: CH in predominantly cancer patients is associated with cardiovascular disease and transformation to myeloid neoplasms, especially in those with higher mutational burdens and anemia. However, patients die more frequently from their primary malignancy or comorbidities than from a myeloid neoplasm. Close monitoring of hematologic progression and extra-hematologic manifestations of CH is crucial. Further investigation into the identification of individuals at high risk of myeloid transformation and potential early therapeutic interventions for this population is warranted.
Lisocabtagene maraleucel (liso-cel) in R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Primary analysis of TRANSCEND CLL 004.
Authors: Siddiqi Tanya , Maloney David G. , Kenderian Saad , Brander Danielle M. , Dorritie Kathleen Anne , Soumerai Jacob , Riedell Peter A. , Shah Nirav Niranjan , Nath Rajneesh , Fakhri Bita , Stephens Deborah Marie , Ma Shuo , Feldman Tatyana A , Solomon Scott R. , Schuster Stephen J. , Perna Serena K. , Ou San-San , Papp Eniko , Chen Yizhe , Wierda William G. 
Published: June 2023

7501 Background: In patients (pts) with R/R CLL/SLL that progressed on BTKi and failed venetoclax (ven)-based regimens, achieving CR with current treatment is uncommon. New therapies that achieve deep and durable responses are needed. We report the primary analysis of the phase 1/2, single-arm, multicenter TRANSCEND CLL 004 (NCT03331198) study evaluating liso-cel in pts with R/R CLL/SLL. Methods: Pts must have received at least 2 prior lines of therapy, including a BTKi. Eligible pts received liso-cel at a target dose of either 50 (DL1) or 100 (DL2) × 106 CAR+ T cells. The primary endpoint was rate of CR and CR with incomplete marrow recovery (CRi) by IRC per 2018 iwCLL criteria in the prespecified subset of efficacy-evaluable pts with disease progression on BTKi and ven failure (primary efficacy analysis set [PEAS]) at DL2 (null hypothesis [H0]: ≤ 5%). Key secondary endpoints were ORR (H0: ≤ 40%) and rate of undetectable minimal residual disease (uMRD; 10−4) in blood (H0: ≤ 5%). Results: Of 137 leukapheresed pts, 117 received liso-cel (safety set), 96 (DL1 = 9; DL2 = 87) were efficacy evaluable, and 53 (DL1 = 4; DL2 = 49) were in the PEAS. In the safety set, median (range) age was 65 y (49–82), 83% had high-risk features, median (range) lines of prior therapy was 5 (2–12), and all pts had prior BTKi. Median (range) on-study follow-up was 21.1 mo (0.4–55.6) for the safety set. In the PEAS at DL2, the primary endpoint of CR/CRi rate was met at 18.4% (95% CI, 8.8–32.0; 1-sided P = 0.0006; Table). ORR was 42.9% and was not statistically significant (95% CI, 28.8–57.8; 1-sided P = 0.3931). The uMRD rate was 63.3% in blood and 59.2% in marrow. Median (95% CI) DOR was 35.3 mo (11.01–not reached [NR]) with a median follow-up of 19.7 mo. Median duration of CR/CRi was NR. In the safety set, rate of any-grade CRS was 84.6% (gr 3, 8.5%; no gr 4/5) and neurological events (NE) was 45.3% (gr 3, 17.9%; gr 4, 0.9%; no gr 5); 69.2% received tocilizumab and/or corticosteroids for CRS/NEs. Rate of gr ≥ 3 infections, hypogammaglobulinemia, and prolonged cytopenia was 17.1%, 15.4%, and 53.8%, respectively. One death related to liso-cel was due to hemophagocytic lymphohistiocytosis. Liso-cel exhibited rapid in vivo expansion and was detected by qPCR in blood up to 36 mo after infusion. Conclusions: Liso-cel demonstrated durable CR/CRi, high uMRD rates, and a manageable safety profile in pts with heavily pretreated, high-risk R/R CLL/SLL and high unmet need. Clinical trial information: NCT03331198 . [Table: see text]
Epcoritamab + R2 regimen and responses in high-risk follicular lymphoma, regardless of POD24 status.
Authors: Merryman Reid , Belada David , Sureda Anna , Leppä Sirpa , Vermaat Joost S.P. , Holte Harald , Hutchings Martin , Lugtenburg Pieternella , de Vos Sven , Abrisqueta Pau , Nijland Marcel , Christensen Jacob Haaber , Wahlin Björn E. , Linton Kim M. , Wang Liwei , Abbas Aqeel , Rana Ali , Quadri Syed , Falchi Lorenzo 
Published: June 2023

7506 Background: Follicular lymphoma (FL) is a heterogeneous disease. Early progression after initial treatment (tx) with chemoimmunotherapy (CIT), POD24, occurs in around 20% of patients (pts) and strongly predicts poor outcomes. There is no standard tx approach for high-risk, relapsed or refractory (R/R) FL (high-risk subgroups in Table). Novel options are needed to improve efficacy in pts with high unmet need. Epcoritamab, a subcutaneous (SC) T-cell–engaging bispecific antibody, demonstrated impressive single-agent antitumor activity and a manageable safety profile in R/R FL (Hutchings et al, Lancet 2021) and shows promise combined with standards of care. Here we present pooled analyses from cohorts 2a and 2b of the ongoing phase 1/2 EPCORE NHL-2 trial (NCT04663347) of epcoritamab with rituximab + lenalidomide (R2). Methods: Pts with R/R CD20+ FL received epcoritamab SC + R2 for 12 cycles (Cs; 28 d each). Epcoritamab was dosed QW in C1–3, Q2W in C4–9, and Q4W in C≥10 (2a) or QW in C1–2 and Q4W in C≥3 (2b) for ≤2 y. Results: As of Oct 31, 2022, 109 R/R FL pts had received epcoritamab 48 mg + R2 in 2a and 2b. Median age was 65 y, 56% of pts had FLIPI 3–5, 61% had stage IV disease, and 59% had only 1 prior tx. Most had received alkylating agents (92%) or anthracyclines (62%); 2 had prior CAR T. At a median follow-up of 8.8 mo (range, 1.2–18.5), 82% were still on tx. The most common tx-emergent AEs were: CRS and neutropenia, 48% each; injection-site reactions, 38%; and fatigue, 33%. CRS events were mostly low grade (G; 46% G1–2, 2% G3) and mostly occurred following the first full dose on C1D15; all resolved and none led to discontinuation. ICANS occurred in 2 pts (G1, G2) and resolved. In 101 efficacy-evaluable pts, overall response rate (ORR) was 97%, with complete metabolic response (CMR) in 86%. Notably, pts achieved higher ORR/CMR rates with epcoritamab + R2 vs their immediate prior tx line (ORR, 97% vs 85%; CMR, 86% vs 60%). Estimated 6-mo progression-free survival was 93%. In second-line (2L) pts with POD24, ORR/CMR rates were 95%/90% (additional high-risk subgroup data in Table). Additional data with longer follow-up will be presented. Conclusions: Epcoritamab + R2 showed potent antitumor activity and a manageable safety profile in a large R/R FL population. Encouraging responses were seen in pts with high-risk disease, suggesting epcoritamab SC may abrogate negative effects of high-risk features. A separate POD24 cohort is planned, and epcoritamab + R2 is being studied in the phase 3 EPCORE FL-1 trial (NCT05409066). Clinical trial information: NCT04663347 . [Table: see text]
Response-adapted therapy (tx) with nivolumab plus brentuximab vedotin (nivo + BV) without autologous hematopoietic cell transplantation (auto-HCT) in children, adolescents, and young adults (CAYA) with low-risk relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL): CheckMate 744.
Authors: Harker-Murray Paul David , Cole Peter D. , Hoppe Bradford S. , Hodgson David C. , Beishuizen Auke , Garnier Nathalie , Buffardi Salvatore , Mascarin Maurizio , Lissat Andrej , Akyol Alev , Crowe Russell , Li Ju , Drachtman Richard A. , Kelly Kara M , Leblanc Thierry , Daw Stephen 
Published: June 2023

7515 Background: Outcomes are poor for patients (pts) with cHL who develop R/R disease after first-line (1L) chemotherapy ± radiotherapy (RT). Salvage tx that attain high event-free survival (EFS) rates and minimize late toxicity by omitting high-dose chemotherapy (HDCT)/auto-HCT are needed. CheckMate 744 (NCT02927769) is the first multicenter phase 2 study evaluating a risk-stratified, response-adapted salvage tx with nivo + BV in CAYA with R/R cHL. In the standard-risk cohort, complete molecular response (CMR) rate before consolidation with HDCT/auto-HCT was 94% (Harker-Murray et al. Blood 2022). With highly active salvage tx, pts in low-risk cohort could achieve high EFS without HDCT/auto-HCT; we report data from this cohort. Methods: Pts were aged 5–30 y and had ≤ 3 cycles (C) of 1L anthracycline-based systemic tx. Risk stratification was described in Harker-Murray et al. Pts received 4C of nivo + BV induction. Pts with CMR received additional 2C nivo + BV before involved-site radiation therapy (ISRT) consolidation (dose, 30–30.6 Gy). Pts with suboptimal response received 2C BV + bendamustine intensification; pts with CMR proceeded to ISRT consolidation. Primary endpoints: CMR rate (Lugano 2014) any time before ISRT and 3-y EFS rate, both per blinded independent central review (BICR). For CMR and overall response rate (ORR), a 90% confidence interval (CI) was used per statistical plan. Results: Among 28 pts treated with nivo + BV, median (range) age was 17 (6–27) y; 64% of pts were aged < 18 y. Most (64%) pts had stage II disease at relapse; 82% had relapse ≥ 12 mo after 1L tx, 2 pts had prior RT. Median (range) follow-up was 31.9 (2.2–55.3) mo. CMR, ORR, 3-y EFS and PFS rates are shown in Table. Median duration of response was not reached; 87% of pts had sustained response at 36 mo’ follow-up. Efficacy outcomes were comparable in the pediatric population (CMR per BICR before ISRT, 88.9%; 3-y EFS rate, 78.3%). During induction, 22 (78.6%) pts had treatment-related adverse events (TRAEs; grade 3/4, 25.0% pts; hematologic, < 10% pts; immune-mediated, 21.4%). Serious AEs leading to discontinuation included rash, pyrexia, and acute kidney injury (1 pt each). Conclusions: The findings demonstrate that most CAYA with low-risk R/R cHL can be salvaged with chemoimmunotherapy with a favorable toxicity profile, and do not require HDCT/auto-HCT. Clinical trial information: NCT02927769 . [Table: see text]
Subgroup analyses of primary refractory (refr) vs early relapsed (rel) large B-cell lymphoma (LBCL) from the TRANSFORM study of lisocabtagene maraleucel (liso-cel) vs standard of care (SOC) as second-line (2L) therapy.
Authors: Nastoupil Loretta J. , Kamdar Manali K. , Chavez Julio C. , Ghesquieres Herve , Ghosh Monalisa , Holmes Houston , López Guillermo Armando , Martinez-Lopez Joaquin , Novak Urban , Ribrag Vincent , Roddie Claire , Waller Edmund K. , Feldman Tatyana A , Rosenthal Allison Claire , Sauter Craig , Von Bonin Malte , Karmali Reem , Montheard Sandrine , Previtali Alessandro , Abramson Jeremy S. 
Published: June 2023

7526 Background: The TRANSFORM primary analysis (PA; NCT03575351) confirmed the superior efficacy of liso-cel vs SOC as 2L therapy in patients (pts) with primary refr or early rel LBCL (Abramson et al. Blood 2022). Response to first-line (1L) therapy (refr vs rel), which was a study randomization stratification factor, may influence future treatment response. Here, we present results for refr and rel LBCL subgroups from the TRANSFORM PA. Methods: TRANSFORM is a randomized phase 3 study of liso-cel vs SOC (salvage chemotherapy [CT] followed by high-dose CT [HDCT]/autologous SCT [ASCT]) in adults ≤ 75 y with LBCL primary refr to or rel ≤ 12 mo after 1L therapy and eligible for HDCT/ASCT. The primary endpoint was event-free survival (EFS); key secondary endpoints were CR rate, PFS, and OS. In this predefined subgroup analysis, refr was SD, PD, PR, or CR with rel < 3 mo after 1L therapy; rel was CR with rel ≥ 3 mo and ≤ 12 mo after 1L therapy. Results: 92 pts were randomized to each arm. Most pts in the liso-cel and SOC arms had refr disease (73% and 76%, respectively; rel disease, 27% and 24%). Baseline characteristics in the refr and rel subgroups, respectively, were generally balanced: median LDH (U/L; liso-cel, 228.5 and 225; SOC, 259 and 259); median SPD (cm2; liso-cel, 11 and 12; SOC, 15.5 and 18); high-grade B-cell lymphoma (liso-cel, 27% and 16%; SOC, 27% and 9%); diffuse LBCL not otherwise specified (liso-cel, 58% and 56%; SOC, 49% and 73%). Consistent with the overall study population, EFS, CR rate, and PFS favored liso-cel vs SOC in both subgroups (Table). Safety was also consistent. Grade ≥ 3 cytokine release syndrome (CRS) and neurological events (NE) were low in refr (1% and 4%) and rel (0 and 4%) subgroups, respectively, with no grade 4/5 CRS or NEs. Conclusions: In TRANSFORM, liso-cel showed benefits in EFS, PFS, and CR rate vs SOC irrespective of prior response to 1L therapy. As refr LBCL is historically difficult to treat, outcomes for liso-cel in this subgroup are encouraging. Clinical trial information: NCT03575351 . [Table: see text]
Patient perspectives on CLL treatment side effects: A sub-analysis of the VOICE survey.
Authors: Tam Constantine Si Lun , Pinilla-Ibarz Javier , Karakus Volkan , Pavlovsky Miguel , Šimkovič Martin , Stilgenbauer Stephan , Fenili Ana Cristina , Miroli Miguel Augusto , Castillo Carolina Garcia , Huntley Kathryn , Moura Catherine , Piotrowski Fernando , Mattar Mervat 
Published: June 2023

7534 Background: Treatment for chronic lymphocytic leukemia (CLL), including chemoimmunotherapy and targeted drugs, is associated with various adverse events. We surveyed patients with CLL about their knowledge and attitudes regarding treatments and “side effects” (SEs), a more widely understood term for adverse events. Methods: Clinicians and patient advocacy group representatives developed and distributed a survey from March through December 2022 in 12 countries to patients with CLL who underwent ≥1 line of treatment. The anonymous survey was available via an electronic platform, digital questionnaires (.pdf), or paper forms. This sub-analysis includes items regarding SEs during treatment intervals, although the SEs queried were not comprehensive. Results: Treatment SEs had a moderate or high impact on 27%–43% of patients in every domain queried (Table). Most patients (300/370; 81%) discussed SEs with their physicians “always” or “sometimes”, but (117/277) were seeking more information about the benefits and SEs associated with their treatment, primarily via the internet. When asked how they would respond to common SEs, most patients would consult their physician first . Notably, >10% of them would continue treatment normally if they experienced arrhythmias or cardiac problems, and 21% would continue if they developed hypertension (Table). A similar proportion (11%) would continue treatment if they had an infection, while 23% of them would consider stopping treatment without medical advice if they developed skin cancer. Conclusions: These results show the impacts of SEs from CLL treatment affect substantial numbers of patients in multiple life areas. The responses suggest that despite patient-physician communication about SEs, there is a need to help patients find reliable information about their treatments online as well. Finally, patients’ willingness to stop or continue treatment in the event of various SEs, including cardiovascular or oncologic events, indicates a critical knowledge gap regarding the risk associated with these events. The real-world data presented herein highlights areas in which improved patient education initiatives could directly improve patient outcomes. [Table: see text]
Real-world (RW) dosing patterns and outcomes among chronic lymphocytic leukemia (CLL) patients (pts) with or without an ibrutinib (IBR) dose adjustment (DA) in first-line (1L).
Authors: Rogers Kerry Anne , Lu Xiaoxiao , Emond Bruno , Ding Zhijie , Lefebvre Patrick , Lafeuille Marie-Hélène , Mavani Heena , Qureshi Zaina P. , Ghosh Nilanjan 
Published: June 2023

7537 Background: Pts treated for CLL with IBR, a once-daily Bruton’s tyrosine kinase inhibitor with dosing flexibility options, may adjust their daily dose to help prevent recurrence or worsening of adverse events, while preserving efficacy. This RW study describes outcomes for CLL pts treated with 1L IBR who did or did not have a DA. Methods: Electronic medical records from the Acentrus database (1/1/2016-4/30/2022) were used to identify CLL pts initiated on 1L IBR (index date). The first 6 months post-index were used to identify pts who remained on a starting dose of 420mg/day or with a DA (reducing to a dose lower than 420mg/day; reasons for DA not available). Treatment adherence (measured by proportion of days covered [PDC] and medication possession ratio [MPR]) and time to next treatment (TTNT) were described for patients with and without a DA. Descriptive analyses are reported for all pts and among a subgroup of pts with high cardiovascular (CV) risk, defined as having a pre-existing CV comorbidity or a high CV risk score (CV subgroup). Results: 1,171 CLL patients were initiated on 1L IBR at the recommended dose of 420mg/day (Table). Of those, 1,038 (88.6%) remained on 420 mg for ≥6 months (mean age=70.2 years, 33.6% female, median follow-up: 30.5 months); 229 (19.6%) had a DA at any time post-index (median time to DA: 5.5 months) and 126 had the DA during the first 6 months (mean age=72.2 years, 42.9% female, median follow-up: 35.1 months). Mean PDC and MPR were descriptively higher in pts with a DA (overall: PDC=0.81, MPR=0.84; CV subgroup: PDC=0.78, MPR=0.81) relative to pts with no DA (overall: PDC=0.70, MPR=0.73; CV subgroup: PDC=0.69, MPR=0.72). Median TTNT was not reached for pts with or without a DA; 12-month Kaplan-Meier (KM) rates were similar for pts with a DA (overall: 89.1%; CV subgroup: 92.7%) and with no DA (overall: 92.5%; CV subgroup: 92.0%). Conclusions: Among CLL pts initiating 1L with standard-of-care IBR, 19.6% had a DA. Those with a DA had descriptively higher treatment adherence with no detriment to TTNT, relative to those who maintained 420mg/day starting dose, regardless of baseline CV risk. These findings are consistent with other RW studies and suggest that IBR DA can be an effective treatment strategy that does not negatively affect efficacy while being well-tolerated outside of clinical trials. [Table: see text]