bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel method for the detection of circulating tumor plasma cells in multiple myeloma.
Authors: Lee Jihyun , Kang Hoin , Kim Soee , Lee Ju Bi , Kim Hyo Yong , Kim Min Hyung , Kim Myeong-Jin , Kim Jungwon 
Published: June 2024

e19520 Background: Multiple Myeloma (MM) is characterized by the proliferation of abnormal plasma cells within the bone marrow. A bone marrow examination is essential for the diagnosis of multiple myeloma. This is a test that causes great pain to patients because it requires collecting and analyzing the bone marrow fluid inside the bone. In addition, there is a disadvantage that it cannot be carried out frequently due to cost issues. Therefore, the development of new diagnostic methods is absolutely necessary. The aim of this study is to access the potential of circulating tumor plasma cells (CTPC) for the diagnosis of MM using CytoGen's Smart Biopsy platform. Methods: Spiking tests using MM cell line (RPMI8226) was conducted with the purpose of making an environment similar to the MM patient's blood. RPMI8226 cells (200 cells) stained with CellTracker were spiked into human blood sample (5mL, healthy donor). Then, spiked cells were isolated by CytoGen’s Smart Biopsy isolator, subsequently recovery rate was accessed by counting of isolated RPMI8226 or immunofluorescence (IF) staining with multiple myeloma-specific marker, CD138. Then, clinical evaluation was performed with bone marrow (3mL) and peripheral blood (5mL) samples of MM patients (n=20). The presence of CTPC in patient samples was tested by IF staining with anti-CD138 antibody. Results: In in vitro experiments to test recovery rate of CTPC using CytoGen's Smart Biopsy isolator, MM cell line’s recovery rate was validated to over 80%. CD138 expression was clearly detected by IF staining of spiking samples of multiple myeloma cell line and was not detected at all in the negative controls. In clinical evaluation study, CTPC was successfully observed after the isolation from bone marrow and peripheral blood using CytoGen's Smart Biopsy isolator by IF staining with CD138. Conclusions: This study shows a novel method for the detection of MM with liquid biopsy. CTPC from liquid biopsy of MM could be isolated using CytoGen's Smart Biopsy isolator with high recovery rate and can clearly be detected with specific marker of MM, CD138 by IF staining. These results suggested that CytoGen's Smart Biopsy platform might be an effective diagnostic tool for the detection of MM. Expanded clinical study will be performed with more MM samples for clinical validation. Clinical trial information: 2013-09-009 .
Efficacy of low-dose direct oral anticoagulants (DOACs) for venous thromboembolism prophylaxis in newly diagnosed multiple myeloma.
Authors: Basali Diana , Zureigat Hadil , Nurse Daniel Paul , Elmaleh Hassan , Batah Heya , Adcock Bridget , Wei Wei , Dima Danai , Valent Jason Neil , Anwer Faiz , Samaras Christy Joy , Khouri Jack , Williams Louis , Raza Shahzad , van Heeckeren Willem Jan , Mazzoni Sandra Ann 
Published: June 2024

e19521 Background: The venous thromboembolism (VTE) risk is high in newly diagnosed multiple myeloma (NDMM) patients, especially within 6 months of beginning treatment and with the use of immunomodulatory-drug (IMiD)-based regimens. SAVED and IMPEDE VTE scores assess risk and NCCN guidelines recommend their use. Few studies have explored optimal thromboprophylaxis agent by risk category which has led to varied treatment strategies. We share our institutional experience using DOACs vs aspirin in NDMM patients and explore incidence of VTE, utility of SAVED and IMPEDE scores, and patient safety. Methods: We retrospectively analyzed outcomes of NDMM patients aged 18 and above from January 2018 to June 2022. Patients receiving anticoagulation for other indications or unable to safely take aspirin or DOACs were excluded. The primary outcome was incidence of VTE in the first 6 months of treatment. Secondary outcomes included patient and treatment factors contributing to VTE risk, comparison of VTE scoring calculators: SAVED vs IMPEDE VTE, and safety of low dose DOAC therapy. Fisher’s exact and Wilcoxon rank sum tests were used to compare patient characteristics between 6-month VTE status. Results: Of 347 NDMM patients that were included, 21% experienced VTE within 6 months. Of those who took aspirin, 20.2% had 6-month VTE. For DOACs, 21.4% taking apixaban and 21.7% taking rivaroxaban had 6-month VTE. There was no significant difference in VTE rate between DOAC or ASA groups (p=0.90). Patients with SAVED score ≥2 (p<0.0006) or prior VTE history (p<0.0001) had significantly higher 6-month VTE rates . Characteristics including age>80, sex, race, BMI>25, IMPEDE score, presence of high-risk cytogenetics, existing use of aspirin or low molecular weight heparin, or transplant status showed no significant difference in VTE rate. Conclusions: This is one of the largest retrospective studies examining efficacy and safety of DOACs in NDMM. Initial analysis showed no significant difference in 6-month VTE rate between NDMM patients treated with aspirin or DOAC therapy. SAVED score appears to delineate high risk VTE patients vs IMPEDE. Follow-up will assess 12-month, 18-month, and overall VTE rates. Bleeding events and analysis for additional high-risk correlates, such as choice of induction regimen, will be presented. This highlights the need for ongoing trials evaluating risk-assigned thromboprophylaxis in patients with MM. [Table: see text]
Clinical outcomes and resource utilization in patients with multiple myeloma admitted with gastrointestinal bleeding.
Authors: Khan Fayaz , Rahima Kenan 
Published: June 2024

e19522 Background: In multiple myeloma (MM) patients, GIB can be due to factors such as abnormal proteins affecting the GI tract, coagulation issues, or secondary conditions like amyloidosis. There's limited scientific evidence examining outcomes among patients presenting with both GIB and MM. Thus, our objective was to assess clinical outcomes in this specific population. Methods: We accessed the National Inpatient Sample from 2017-2020 to identify adult patients with MM hospitalized due to GIB. The primary endpoint was inpatient mortality, with secondary endpoints including length of stay and total hospital charges. We utilized multivariable logistic regression analysis to estimate clinical outcomes, considering a significance threshold of P < 0.05. Results: We identified 4,067,364 hospitalizations with GIB, among which 22,000 (5.9%) presented with MM. Comparing MM and Non-MM cohorts, the mean age was 71.9 vs 67.8 years, males constituted 58% vs 52.2%, and White ethnicity accounted for 55.6% vs 66.1%. The prevalence of obesity was 10.6% vs 14.5%, diabetes mellitus was 32.1% vs 33.8%, chronic obstructive pulmonary disease was 16.9% vs 20.4%, dyslipidemia was 38.5% vs 40.7%, atrial fibrillation was 27.7% vs 25.6%, hypertension was 22.9% vs 34.7%, heart failure (HF) was 30.7% vs 26.4%, peripheral vascular disease (PVD) was 2.9% vs 4.1%, acute kidney injury was 45.6% vs 29.4%, anemia was 26.3% vs 27.7% and chronic kidney disease (CKD) was 51.9% vs 28.6%. Clinical outcomes revealed stark differences between MM and Non-MM cohorts: in-hospital mortality rates were 10.9% vs 6.3% with an odds ratio (OR) of 1.5 (CI 1.4-1.7); LOS was 9.6 days vs 6.7 days (IRR 1.26, CI 1.21-1.32); and hospital charges were $30,006 vs $20,172 (IRR 1.34, CI 1.26-1.42). All data demonstrated a p-value < 0.001 and were adjusted for various factors including age, sex, race, comorbidity indices, obesity, atrial fibrillation, diabetes mellitus, hypertension, peripheral vascular disease, acute kidney injury, chronic kidney disease, nicotine and alcohol use, stroke, acute respiratory failure, and inflation during 2017-2020. Conclusions: Patients hospitalized for GIB and MM were comparatively older, with a larger male population and fewer Caucasians. They exhibited higher Afib, HF, AKI, and CKD rates with lower occurrences of obesity, DM, COPD, dyslipidemia, HTN, anemia and PVD. This group showed a significantly worse mortality rate with prolonged hospital stays and resource utilization. This entails to have prompt medical attention, appropriate management of bleeding, and addressing the underlying causes are crucial in improving outcomes and reducing mortality rates. Treatment strategies often involve a multidisciplinary approach involving oncologists, hematologists, gastroenterologists, and other specialists to provide comprehensive care tailored to the individual's condition.
Phase 3 randomized double-blind study evaluating selinexor, an XPO1 inhibitor, plus ruxolitinib in JAKi-naïve myelofibrosis.
Authors: Mascarenhas John , Maher Keri Renee , Rampal Raajit , Bose Prithviraj , Podoltsev Nikolai Alexandrovich , Hong Junshik , Wang Xulong , Kye Steve , Harrison Claire 
Published: June 2024

TPS6594 Background: Myelofibrosis (MF) is a myeloproliferative neoplasm with common somatic gene driver mutations in JAK2, CALR, and MPL. Selinexor, an investigational oral XPO1 inhibitor, may inhibit MF-relevant JAK/STAT and non-JAK/STAT pathways. Preclinical studies have shown potential synergy with ruxolitinib treatment. In the phase 1 portion of XPORT-MF-034 evaluating selinexor plus ruxolitinib in JAKi-naïve patients with MF, the most common AEs in the 60 mg cohort were nausea (79%), anemia (64%), thrombocytopenia (64%), and fatigue (57%). Nausea was predominantly Grade 1 and transient in nature. Treatment-related AEs leading to treatment discontinuation were thrombocytopenia (n=1) and neuropathy (n=1). SVR35 and TSS50 was achieved by 79% and 58% of the 60 mg cohort intent-to-treat population at Week 24, respectively. Response rates were consistent across subgroups, including sex and regardless of ruxolitinib starting dose. These data provide strong support to further evaluate selinexor (60 mg) and ruxolitinib in patients with JAKi-naïve MF. Methods: The XPORT-MF-034 (NCT04562389) trial includes a global, Phase 3 randomized, double-blind, placebo-controlled study designed to evaluate selinexor and ruxolitinib. JAKi-naïve patients with MF will be randomized 2:1 to receive oral selinexor 60 mg or placebo once weekly (28-day cycle) and twice daily ruxolitinib. Randomization will be stratified by DIPSS risk category (int-1 vs int-2 or high-risk), spleen volume (<1800 cm3 vs >1800 cm3 by MRI/CT scan), and baseline platelet counts (100-200x109/L vs >200x109/L). Dual anti-emetics for nausea prophylaxis will be required for the first two cycles. Select eligibility criteria include ≥18 years of age, spleen volume ≥450 cm3 by MRI or CT, DIPSS intermediate-1, intermediate-2, or high-risk, active symptoms of MF (MFSAF v4.0), currently not eligible for stem cell transplantation, ECOG≤2, and platelet count ≥100 x 109/L. Select exclusion criteria include >10% blasts in peripheral blood or bone marrow; previous treatment with JAKi for MF, or previous treatment with selinexor or other XPO1 inhibitors. The co-primary study endpoints are SVR35 and TSS50 at Week 24 and will be tested hierarchically. The key secondary endpoint is anemia response at Week 24 per the IWG-MRT and ELN criteria. The XPORT-MF-034 Phase 3 trial is currently open for enrollment; a total of 306 JAKi-naïve MF patients will be enrolled and the study was initiated on June 28, 2023. Clinical trial information: NCT04562389 .
EPCORE FL-2: Phase 3 trial of epcoritamab with rituximab and lenalidomide (R2) vs chemoimmunotherapy or R2 in previously untreated follicular lymphoma.
Authors: Linton Kim M. , Thompson Philip , Luminari Stefano , Casulo Carla , Patah Poliana , Zeng Lingmin , Mei JP , Dixit Neha , Hoehn Daniela , Bachy Emmanuel 
Published: June 2024

TPS7084 Background: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma. Most patients with advanced-stage FL in need of systemic therapy are treated with an anti-CD20 monoclonal antibody (eg, rituximab [R] or obinutuzumab [G]) with cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] or bendamustine [benda]). Recent studies have shown R plus lenalidomide (R2) is a potent FL treatment in the 1L and relapsed or refractory (R/R) settings and is a promising backbone for combination therapies. Epcoritamab, a subcutaneous CD3xCD20 bispecific antibody, received breakthrough therapy designation by the FDA for R/R FL after ≥2 lines of systemic therapy. In the phase 1/2 trial (NCT04663347), epcoritamab plus R2 demonstrated high complete response (CR) rates in the 1L and R/R settings. The objective of this trial is to evaluate the safety and efficacy of 1L epcoritamab plus R2 vs CIT in patients with FL. Methods: EPCORE FL-2 (NCT06191744) is a global, randomized, open-label phase 3 trial. Eligible adult patients must have CD20+ histologically confirmed classic FL (previously grade 1–3A), stage III or IV disease (or bulky stage II), and in need of systemic treatment by meeting GELF criteria. Approximately 1080 patients will be randomized to 3 treatment arms (Table). Patients achieving CR or PR upon 6 cycles will move to epcoritamab on day 1 of cycles 7–12 (28-day cycles) and 13–21 (56-day cycles). After 120 weeks of treatment, patients will be followed for progression and survival. Dual primary endpoints will be CR rate at 30 months and progression-free survival in arm A vs arm B. Key secondary efficacy endpoints include overall survival, minimal residual disease negativity, and changes in patient-reported outcomes on the physical functioning scale of the European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire from baseline to week 25. Safety endpoints include incidence and severity of adverse events (AEs), including AEs of special interest (cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, and clinical tumor lysis syndrome). The study is open for enrollment. Clinical trial information: NCT06191744 . [Table: see text]
CELESTIAL-TNCLL: An ongoing, open-label, multiregional, phase 3 study of sonrotoclax (BGB-11417) + zanubrutinib vs venetoclax + obinutuzumab for treatment-naïve (TN) CLL.
Authors: Shadman Mazyar , Kater Arnon P. , Woyach Jennifer Ann , Li Jianyong , Munir Talha , Salmi Tommi , Phuong Patrick , Tian Tian , Patten Piers 
Published: June 2024

TPS7087 Background: The combination of venetoclax (ven), the first-generation BCL2 inhibitor, and ibrutinib, a BTK inhibitor, has demonstrated efficacy in patients with CLL (Wierda et al. J Clin Oncol. 2021); however, the toxicity profile of this regimen suggests a need for a more tolerable BTK/BCL2 inhibitor combination. Sonrotoclax, a next generation BCL2 inhibitor, is a more selective and more pharmacologically potent inhibitor of BCL2 than venetoclax. In a phase 1 study in patients with TN CLL treated with sonrotoclax + zanubrutinib, efficacy data was promising with ORR and 1-year progression-free survival (PFS) rates of 100% and deep responses based on undetectable measurable residual disease at <10-4 sensitivity (uMRD4). The most common grade ≥3 TEAE was neutropenia, and no tumor lysis syndrome or cardiac toxicity was observed (Tam et al. Blood. 2023). Zanubrutinib, a next-generation BTK inhibitor, significantly improved PFS and had a more tolerable safety profile, including fewer cardiac adverse events vs ibrutinib in a randomized, head-to-head study of patients with CLL/SLL (Brown et al. N Engl J Med. 2023). Presented here is the design of a phase 3 trial aimed at comparing the efficacy of sonrotoclax + zanubrutinib vs ven + obinutuzumab (obi) in patients with TN CLL. Methods: CELESTIAL-TNCLL (BGB-11417-301; NCT06073821) is a randomized, open-label, phase 3 study. Eligible patients must have previously untreated CLL that requires treatment per 2018 iwCLL criteria, measurable disease by CT/MRI, an ECOG performance score of 0-2, and adequate hematologic and organ function. Approximately 640 patients will be randomized 1:1 to receive either 3 cycles of zanubrutinib monotherapy (320 mg total daily dose, orally), followed by zanubrutinib + sonrotoclax for 12 cycles, or standard ven + obi treatment for 12 cycles. Randomization will be stratified by age (<65 vs ≥65 years) and IGHV and del(17p)/ TP53 mutation status. The primary endpoint is PFS as assessed by independent review committee (IRC) according to 2018 iwCLL guidelines with modifications for treatment-related lymphocytosis for patients with CLL (Cheson et al. 2012). Key secondary endpoints include complete response rate (CRR), defined as CR or CR with incomplete hematopoietic recovery, assessed by IRC; rates of uMRD4 in bone marrow and peripheral blood at the first post-treatment follow-up visit based on next-generation sequencing by clonoSEQ; and overall survival. Other secondary endpoints include PFS as assessed by investigator (INV); CRR by INV; rate of uMRD4 based on flow cytometry; overall response rate by IRC and INV; duration of response by IRC and INV; patient-reported outcomes; and safety and tolerability. Recruitment is ongoing. Clinical trial information: NCT06073821 .
First-line treatment of follicular lymphoma (FL) with golcadamide, rituximab +/- nivolumab: An umbrella randomised phase 2 investigator-led study.
Authors: Chong Geoffrey , Palmer Jodie , Barraclough Allison , Churilov Leonid , Keane Colm , Lee Sze Ting , Lee Denise , Ratnasingam Sumita , Smith Charmaine , Hawkes Eliza Anne 
Published: June 2024

TPS7092 Background: The most common therapy FL pts receive remains chemotherapy which yields high efficacy but also significant toxicity.(Marcus 2017, Rummel 2013). FL pts are largely aged over 65 and may require treatment multiple times over their disease course thus novel regimens which enhance efficacy and minimise toxicity are highly desirable. FL patient (pt) outcomes are influenced by tumor microenvironment composition and manipulation with immunotherapy. Ikaros and Aiolos, key cell development and homeostasis transcription factors are upregulated in FL. Cereblon-modulating compounds (CELMoDs) such as golcadomide (G) promote degradation of these with demonstrated efficacy alone or with rituximab (R) in FL (responses-ORR- upto 75% in heavily pre-treated FL pts) (Morschhauser 2018, Michot 2021). We reported favourable efficacy of nivolumab (N) a PD1 inhibitor plus R in 1L treatment of FL (ORR 92% complete response CR 54%). (Hawkes 2021).This study (‘TOP-FLOR’; NCT05788081) builds on these findings and potential immunomodulatory synergy to explore the efficacy and safety of R + G, a novel CELMoD +/- N in treatment-naïve advanced stage FL pts. Methods: This is an open label multicentre umbrella Bayesian Optimal randomised Phase 2 trial (n=40). Eligibility includes: age >18 years, treatment-naïve, stage II-IV, low grade FL, ECOG 0-2. Pts from 5 Australian sites are randomised 1:1 to receive 8 cycles of R-G +/-N 8 cycles of 28 days (D) each as follows: Arm A; R 375 mg/m2 IV D1 + G 0.4 mg orally D1- 14; Arm B; R-G as above +N 480mg IV D1. All pts in partial response (PR) or CR post cycle 8 receive 8 doses of 12-weekly R maintenance. The primary endpoint (EP) is CR rate post induction in the absence of prohibitive toxicity (CTCAE V5.0). Secondary EP are overall toxicity, ORR (as per Lugano criteria), time to treatment failure, progression free survival, overall survival. Exploratory EP include: pt reported outcomes, PET radiomics, laboratory biomarkers. Study assessments include safety assessments every cycle until D28 post final study drug delivery. Response assessments (PET/CT), pt reported outcomes & biomarker bloods are performed at baseline, post cycles 2, 5 & 8, then 6 monthly during R maintenance. Futility analysis occurs after 11 pts are recruited to each arm with < 7 pts achieve the primary EP. Treatment arms will not be formally compared. Kaplan-Meier analysis will be used to report survival probabilities. This trial received IRB approval on 14 July 2023 (HREC/88597/Austin-2023). To date 15 pts have been randomised. Clinical trial information: NCT05788081 .
A phase 1/2, open-label, multicenter trial investigating the safety, tolerability, and preliminary antineoplastic activity of IPH6501, a first-in-class NK cell engager, in patients with relapsed and/or refractory CD20-expressing non-Hodgkin lymphoma.
Authors: Falchi Lorenzo , Walker Patricia , Presgrave Peter , Gregory Gareth P. , Marie Delphine , Leyco A.J. , Demaria Olivier , Le Floch François , Hanekom Wouter , Bonin Cecile , Paturel Carine , Quaratino Sonia 
Published: June 2024

TPS7095 Background: The therapeutic landscape for relapsed and/or refractory B-cell non-Hodgkin lymphoma (B-NHL) is evolving to include targeted T-cell based immunotherapies. However, there remains an unmet medical need for patients who are refractory to, relapsing from, or are ineligible for these therapies. Leveraging natural killer (NK) cells emerges as a promising strategy, as demonstrated in a Phase 1 study with IPH6101/SAR’579 in R/R AML (Stein, ASCO 2023; Bajel, ASH 2023), and offers a novel approach that could complement or provide an alternative to T-cell therapies. IPH6501 is a first-in-class tetraspecific antibody-based NK cell engager that simultaneously targets the CD16a and NKp46 receptors on NK cells and CD20 on B-NHL cells. It also includes an engineered IL-2 variant designed with mutations to avoid binding to CD25 (IL-2Rα), limiting Treg activation and potential IL-2 related side effects, whilst inducing NK proliferation. In preclinical animal models, IPH6501 boosted NK cell proliferation and activation, and CD20+ target cell elimination in peripheral blood and tissues, at well-tolerated doses. In samples obtained from R/R B-NHL patients, IPH6501 demonstrated greater killing efficacy compared to a CD3xCD20 T-cell engager, and yet lower cytokine secretion, suggesting a potentially safer profile. Methods: This is a global first-in-human, multicenter, open-label Phase 1/2 study to evaluate the safety profile (DLTs and MTD), tolerability according to NCI-CTCAE v5.0 and to determine the RP2D of IPH6501 for patients with B-NHL (NCT06088654). Secondary objectives are to characterize the pharmacokinetic profile and evaluate the immunogenicity of IPH6501. Eligible subjects are aged ≥18 years with advanced, histologically confirmed, CD20+ B-NHL with an ECOG PS ≤2, and without established alternative therapy. Subjects must have received ≥2 prior systemic therapies which may have included astem cell transplant or CAR-T cell therapy. The Phase 1 part of the study will consist of a dose escalation part which will follow a3+3 design to determine the MTD or the highest dose to be tested as defined in protocol if the MTD has not been reached, and a dose assessment part to randomize ≥2 dose levels to determine the RP2D. The Phase 2 part will enroll one or more cohorts of selected B-cell NHL subtypes to be determined at a later stage. Up to 184 subjects will be enrolled, and the study is open in the United States, Australia and Europe. Clinical trial information: NCT06088654 .