tbuckley/cabot-search huggingface dataset:
Seven-year overall survival analysis from ECHELON-1 study of A+AVD versus ABVD in patients with previously untreated stage III/IV classical Hodgkin lymphoma.
Authors: Stephen M. Ansell, David J. Straus, Joseph M. Connors, Wojciech Jurczak, Won-Seog Kim, Andrea Gallamini, Radhakrishnan Ramchandren, Jonathan W. Friedberg, Ranjana H. Advani, Martin Hutchings, Andrew M. Evens, Kerry J. Savage, Hyeon-Seok Eom, Tatyana A Feldman, Jeremy S. Abramson, Cassie Dong, Bipin N. Savani, Athanasios Zomas, Keenan Fenton, John Radford
Journal: Journal of Clinical Oncology (2024)

7053 Background: In ECHELON-1 (NCT01712490), 6-year follow-up (FU) analyses demonstrated significant improvements in overall survival (OS) and progression-free survival (PFS) with A+AVD (brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine) versus ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), with a comparable safety profile. Here, we report data at 7-year median FU. Methods: Analyses of OS and PFS per investigator were conducted in the intent-to-treat (ITT) population (data cut-off March 11, 2023). Patients (pts) were randomized 1:1 to receive ≤6 cycles of A+AVD (n=664) or ABVD (n=670) on days 1 and 15, every 28 days. PET scan after cycle 2 (PET2) evaluation was mandatory. Long-term safety outcomes in the safety population included resolution or improvement of peripheral neuropathy (PN), second malignancies, and pregnancies. Results: At median FU of 89.3 months (95% CI 87.0–90.2), 7-year OS rates were 93.5% (95% CI 91.1–95.2) with A+AVD and 88.8% (95% CI 85.8–91.1) with ABVD; OS favored A+AVD over ABVD (HR 0.62; 95% CI 0.42–0.90; p=0.011). Subgroup analyses showed consistent OS benefit for A+AVD, including in the age &lt;40 years and Stage IV disease subgroups (Table). 7-year PFS rates with A+AVD vs ABVD were 82.3% (95% CI 79.1–85.0) vs 74.5% (95% CI 70.8–77.7; HR 0.68 [95% CI 0.53–0.86]; p=0.001). PN improved/resolved in most pts at last FU (A+AVD: 86%; ABVD: 87%). Median (range) time to complete resolution of PN (A+AVD vs ABVD) was 16 (0–373) vs 10 (0–343) weeks; median (range) time to improvement was 42 (2–182) vs 19 (15–142) weeks. PN was ongoing in 28% (4% grade ≥3) of A+AVD and 20% (1% grade ≥3) of ABVD pts. Second malignancies were reported in 5% of A+AVD and 6% of ABVD pts. Pts and their partners reported 84/92 livebirths/pregnancies with A+AVD and 59/73 with ABVD; no stillbirths were recorded. Conclusions: At 7-year median FU, pts with stage III/IV cHL who received A+AVD showed a sustained PFS and OS benefit vs ABVD, with PFS rates indicating potential curability. The safety profile in pts treated with A+AVD showed no new safety signals at 7 years. Clinical trial information: NCT01712490 . [Table: see text]
Secondary myeloid malignancy after CAR T cell therapy for non-Hodgkin lymphoma (NHL).
Authors: Alma Habib, Rina Welkie, Jacob Butman, Pedro C Silberman, Jose Vicente Forero, Yazeed Sawalha, Beth Christian, Kami J. Maddocks, Narendranath Epperla, Samantha Mary Jaglowski, David Alan Bond, Hannah Kyung Choe, Jonathan Edward Brammer, Adam Kittai, Evandro Bezerra, Timothy Voorhees, Sumithira Vasu, Sarah Allison Wall, Marcos J.G. De Lima, Nathan Denlinger
Journal: Journal of Clinical Oncology (2024)

7033 Background: Prior studies have described toxicities associated with chimeric antigen receptor T cell therapy (CART). Recently, myeloid malignancies were identified in myeloma patients (pt) after receipt of cilta-cel. In this study, we sought to describe the cumulative incidence and characteristics of secondary myeloid malignancies in pt treated with CART for NHL. Methods: We conducted a single institution retrospective study among pt ages ≥18 years (yr) who received commercial CART for NHL at Ohio State between December 2017 to April 2022. Descriptive statistics were used to summarize pt/disease characteristics. Cumulative incidence was calculated from date of infusion with death/relapse as competing risks. Results: For 190 pt treated with CART, median age was 63 yr (23-85 yr). Disease subtypes included diffuse large B-cell lymphoma (BCL)/high grade BCL, Richter transformation, and mantle cell lymphoma (79.5%, 8.4%, and 7.4%). Products included tisa-cel (47.9%), axi-cel (43.1%), brexu-cel (7.4%), and liso-cel (1.6%). Grade 3-4 neutropenia developed in 29% and 18% of pt at 30 days and 90 days post-CART. Median follow-up was 17 mo (0.5-63 mo). 48% were alive at time of analysis. Myeloid malignancy post-CART occurred in 7 pt with a median time to development of 29 mo (18-41 mo). Characteristics (Table) included complex karyotype, TP53 and chromosome 5/7 abnormalities. Cumulative incidence of secondary malignancy was 1%, 5%, and 6% at 2, 3, and 4 yr post-CART. Conclusions: We report on incidence of secondary myeloid malignancy in pt receiving CART for NHL. Mutational characteristics of secondary malignancies were those classically associated with therapy-related myeloid malignancy, thus presumed to be associated with prior exposure to chemotherapy (eg. alkylators/VP-16). Further investigation in larger cohorts with additional observation time, to allow for appropriate risk discussion, is required. [Table: see text]
AB1731 Efficacy and safety of intravenous Zolidronic acid in the treatment of pediatric osteogenesis imperfecta: a systematic review
Authors: S. Bouden, I. Mahmoud, L. Rouached, A. Ben Tekaya, R. Tekaya, O. Saidane, L. Abdelmoula
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Osteogenesis imperfecta (OI) is an inherited clinically heterogenous disorder of bone metabolism characterized by bone and skeletal fragility and an increased risk of fractures. Pamidronate infusion was the standard treatment, but zoledronic acid is increasingly used to treat children with OI. <h3>Objectives:</h3> We conducted a systematic literature review to evaluate the efficacy and safety of intravenous zoledronic acid in the treatment of OI in pediatric patients. <h3>Methods:</h3> A systematic review of the published literature was performed according to the PRISMA guidelines. Eligible articles were clinical trials and observational studies including pediatric patients (&lt; 16 years) with OI treated with zoledronic acid. We selected articles published during the 20 past years. The selected languages were english and french. We included articles with a minimum sample size of five patients. <h3>Results:</h3> Six articles fulfilled the selection criteria. Majority of patients were Chinese (58%).The predominant sex was male (65%), and the age of included patients ranged from 2.5 weeks to 16.8 years. For all patients, zoledronic infusions were administrated intravenously. The zoledronic treatment duration ranged from 1 to 3 years. Densitometry parameters before and after zoledronic treatment were evaluated and showed significant improvement both in LS-BMD Z-score and FN-BMD Z-scores. A significant decrease in fracture rate has also been noted both in vertebral and nonvertebral fracture incidence. The two most common side effects were fever and flu-like reactions. None of the patients presented severe adverse events. <h3>Conclusion:</h3> zoledronic acid appeared to be safe and effective in the treatment of pediatric OI. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
CODOX-M/IVAC-R versus DA-EPOCH-R in double/triple-hit large B cell lymphoma in patients ≤ 60 years.
Authors: Suheil Albert Atallah-Yunes, Matthew J. Rees, Thomas E. Witzig, Thomas Matthew Habermann, Ellen D McPhail, Javier Munoz, Madiha Iqbal, Grzegorz S. Nowakowski
Journal: Journal of Clinical Oncology (2024)

7067 Background: High intensity induction with regimens such asDA-EPOCH-R, CODOX-M/IVAC-R and HyperCVAD are often used for young patients with DHL/THL despite no overall survival (OS) benefit compared to R-CHOP. Reports on the application of CODOX-M/IVAC-R are subject to selection bias as only young fit patients can tolerate it. We aimed to investigate outcomes difference between CODOX-M/IVAC-R and DA-EPOCH-R in patients ≤ 60 years with DHL/THL diagnosed via FISH. Methods: Retrospective review of DHL/THL patients from the Mayo Clinic diagnosed between July15 th 2010-October19th 2023 treated with CODOX-M/IVAC-R or DA-EPOCH-R at age of up to 60 years. Event free survival (EFS) was defined as time from diagnosis to progression, relapse, next line of treatment or death from any cause. Results: 113 patients were included; CODOX-M/IVAC-R (N=49) and DA-EPOCH-R (N=64). Patient and disease characteristics are in table. 80% (N=39) achieved CR on end of treatment (EOT) PET CT with CODOX-M/IVAC-R compared to only 58% (N=37) with DA-EPOCH-R. CODOX-M/IVAC-R was associated with superior EFS on univariate (HR=0.54, 95%CI=0.31-0.97) and multivariable analysis adjusted for age, BCL2 vs BCL6 translocation and receipt of consolidation ASCT (aHR=0.53, 95%CI=0.29-0.95), however, there was no significant influence on OS (aHR=0.97, 95%CI=0.50-1.91). At a median follow-up of 5.3 years and 3.3 years for the CODOX-M-IVAC and DA-R-EPOCH group respectively; EFS was superior in the CODOX-M/IVAC-R group having 1, 2 and 5 years EFS of 68.3%, 64.1 and 61.5% respectively compared to 52.4%, 48.9% and 39.5% respectively in the DA-EPOCH-R group (p=0.035). 33%(16/49) of the CODOX-M/IVAC-R patients had R/R disease (No CR on EOT PET CT or relapsed) with a median OS of 10.3 months compared to 33.7 months in the R/R DA EPOCH-R group (54%, 35/64). Number of patients who were able to receive salvage ASCT, CAR T and Allo-SCT were 5, 17 and 4 respectively in the DA EPOCH-R group compared to 1, 6 and 3 patients respectively in the CODOX-M/IVAC-R group. None died of regimen toxicity in both groups. 19% underwent ASCT consolidation after CR with initial induction (11 patients in each group); no OS was noticed however consolidation with ASCT was associated with increased EFS regardless of the induction regimen with best outcomes being in the CODOX-M/IVAC-R group (P=0.0072). Conclusions: Our study showed that young patients with DHL/THL who received CODOX-M/IVAC-R had superior EFS compared to DA-EPOCH-R with no OS benefit. CODOX-M/IVAC-R can spare patients receiving more subsequent therapies. Patients who have R/R disease following CODOX-M/IVAC-R have poor outcomes. [Table: see text]
AB1705 TIME AND TREATMENT AS KEY FACTORS IN THE DEVELOPMENT OF UVEITIS IN JUVENILE IDIOPATHIC ARTHRITIS
Authors: H. M. Amar Muñoz, D. Clemente, A. Boteanu, A. García Fernández, L. Ibares, I. Valls, J. C. Lopez Robledillo, I. Monteagudo, J. C. Nieto González
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Juvenile idiopathic arthritis (JIA) represents the most closely associated inflammatory disease with pediatric uveitis, being its most common extra-articular manifestation (10-30%). The majority of JIA patients will develop uveitis within the first four years from the onset of arthritis. Screening guidelines based on risk factors are recommended. Evidence supports the early introduction of systemic immunosuppressive drugs, such as methotrexate and adalimumab, to control intraocular inflammation and prevent associated complications. <h3>Objectives:</h3> The study objectives are to analyze factors associated with the development of uveitis. <h3>Methods:</h3> We conducted a retrospective, longitudinal, multicenter study. Patients with non-infectious uveitis associated with JIA were selected from a multicenter cohort. The time of onset of uveitis was analyzed, as well as the presence of associated complications. Known risk factors (age, gender, antinuclear antibodies (ANAs), JIA subgroup according to the ILAR classification) have been examined. Furthermore, the treatment (systemic immunosuppressive drugs) received by patients with JIA when they developed uveitis was evaluated, along with its duration. <h3>Results:</h3> Out of a total of 404 patients with JIA, we included 77 (19%) who had a diagnosis of uveitis (75% anterior chronic uveitis), of whom 18.2% experienced ophthalmological sequelae. 72 had arthritis preceding (54.5% persistent oligoarticular JIA), mostly girls (73%), with positive ANAs (61%). 37.5% developed uveitis within the first 12 months from diagnosis (Figure 1) with a median time to uveitis of 1.6 years. 74 patients received methotrexate, with a median duration of 3 years. In the first uveitis flare, 24 patients were being treated with methotrexate, and 6 with etanercept (Figure 2). Among patients who discontinued methotrexate before the onset of uveitis, the median time until its appearance was 1.7 years. <h3>Conclusion:</h3> Our study confirms that uveitis develops in the early years following the diagnosis of JIA, but the risk of occurrence persists throughout the course of the disease. More than half of the patients developed uveitis while not receiving systemic treatment. We observed that those receiving methotrexate as monotherapy had a higher frequency of uveitis compared to other treatments. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
Incidence of central nervous system relapse in primary mediastinal B-cell lymphoma: Implications for central nervous system prophylaxis.
Authors: Izel Okcu, Jihao Zhou, Yucai Wang, Allison Marie Bock, Muhamad Alhaj Moustafa, Firas Baidoun, Han W. Tun, Allison Claire Rosenthal, Patrick B. Johnston, Brian Kabat, Lisa M. Rimsza, Thomas Matthew Habermann, Grzegorz S. Nowakowski
Journal: Journal of Clinical Oncology (2024)

7080 Background: Primary mediastinal large B-cell lymphoma (PMBCL) is an uncommon type of aggressive B-cell non-Hodgkin lymphoma. PMBCL has distinct clinicopathologic features compared to diffuse large B-cell lymphoma but shares some clinical and biologic features with nodular sclerosis classic Hodgkin lymphoma (cHL). Central nervous system (CNS) relapse is exceedingly rare in cHL, therefore one may expect that CNS relapse in PMBCL is also uncommon. Herein, we examined the incidence of CNS relapse in patients with PMBCL. Methods: Patients with newly diagnosed PMBCL seen at Mayo Clinic between 1/2002 and 4/2023 were identified from the Mayo Clinic Lymphoma Database. Clinical features, treatment details and outcomes were abstracted from medical records. The CNS relapse rate was calculated using a competing risk model, with death considered as a competing risk. Results: A total of 154 PMBCL cases were identified. The median age at diagnosis was 38 years (range 18-77) and 60.4% were female. The distribution of CNS-IPI was low-risk in 80 (51.9%) patients, intermediate-risk in 43 (27.9%), and high-risk in 3 (1.9%), and data were missing for 28 patients (18.2%). 78 patients (50.6%) received R-CHOP and 76 patients (49.4%) received R-DA-EPOCH as frontline therapy. High-dose methotrexate (HD-MTX) for CNS prophylaxis was administered to 5 patients (all treated with R-CHOP). 20 patients received intrathecal (IT) chemotherapy (methotrexate and/or cytarabine) for CNS prophylaxis (4 with R-CHOP [1 received HD-MTX too],16 with R-DA-EPOCH). The median follow-up was 39 months (95% CI 28.2-49.8). Only 3 patients had CNS relapse, all associated with systemic relapse (1 concurrent, 1 had CNS relapse 8.8 months after systemic relapse, 1 had CNS relapse 2 months before systemic relapse). The cumulative incidence of CNS relapse for the entire cohort was 1.43% (95% CI 0.3%-4.6%) at 1 year and 2.21% (95% CI 0.6%-5.8%) at both 2 and 5 years. For those who did not receive CNS prophylaxis (n=130), the incidence was 0.86% (95% CI 0.1%-4.3%) at 1 year and 1.82% (95% CI 0.4%-5.8%) at both 2 and 5 years. All 3 patients who experienced CNS relapse had R-CHOP as frontline therapy; two patients did not receive any CNS prophylaxis, while 1 patient received IT CNS prophylaxis. Conclusions: The risk of isolated CNS relapse in PMBCL appears to be very low, even in patients who did not receive CNS prophylaxis. While some patients may experience CNS relapse associated with systemic relapse, the overall incidence was low (1.43% at 1 year and 2.21% at 2 and 5 years). The rarity of isolated CNS relapse in PMBCL suggests that routine CNS prophylaxis may not be necessary as part of initial therapy.
AB1621-HPR PREDICTORS OF KINESIOPHOBIA IN INDIVIDUALS WITH OSTEOARTHRITIS FOLLOWING UNILATERAL KNEE ARTHROPLASTY
Authors: G. I. Kinikli, D. Demirtunc Sevim, S. N. Aslan, B. Atilla
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> It is known that kinesiophobia develops in individuals with OA after Total Knee Arthroplasty (TKA). In the existing literature, there is a notable absence of studies examining both preoperative and postoperative functional assessments, as well as perioperative factors triggering kinesiophobia in individuals undergoing total knee arthroplasty. <h3>Objectives:</h3> This study aims to determine the factors that trigger kinesiophobia in individuals with osteoarthritis following unilateral knee arthroplasty. <h3>Methods:</h3> The Brief Fear of Movement Scale (BFoM), Oxford Knee Score (ODS) and 2 Minute Walk Test (2-MWT) were administered to 45 patients who will undergo total knee arthroplasty on preoperative day 1 and postoperative month 3. Range of motion were recorded with a Universal Goniometer and physical characteristics and sociodemographic data were noted. <h3>Results:</h3> A moderate positive correlation (r=0.336, p=0.024; r=0.418, p=0.004) was found between postoperative kinesiophobia and postoperative fear of falling and postoperative extension limitation in 45 volunteers (33 females, 12 males) with a mean age of 64.16±7.50 years. There was a moderate positive correlation between postoperative kinesiophobia and preoperative and postoperative ODS scores (r=0,300; p=0,045; r=0,529; p&lt;0,001). There was a moderate negative correlation (r=-0.384, p=0.009) between postoperative kinesiophobia and postoperative active flexion range of motion. No significant correlation was found between the BFoM and age, weight, BMI (body mass index), degree of passive knee flexion after surgery, degree of active and passive knee extension after surgery and 2-MWT. Low degree of active knee flexion was found to be one of the most effective factors explaining %70 of postoperative kinesiophobia (R<sup>2</sup>=0.70; p&lt;0.001). <h3>Conclusion:</h3> In conclusion of our study, it was found that the most influential factors contributing to postoperative kinesiophobia were the presence of knee extension limitation before surgery, low 2-MWT distances in the postoperative period and low degree of active knee flexion in the postoperative period. As a result of our study, it is conceivable that the evaluation of joint range of motion and functional performance of individuals with osteoarthritis undergoing total knee arthroplasty, which we have emphasized as crucial, can inform the design of rehabilitation programs. Hence, the revelation of a positive impact on postoperative kinesiophobia levels among patients is anticipated. <h3>REFERENCES:</h3> [1] Doury-Panchout F, Metivier JC, Fouquet B. Kinesiophobia negatively influences recovery of joint function following total knee arthroplasty. Eur J Phys Rehabil Med. 2015;51(2):155-61. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
Long-term survival outcomes in patients with relapsed/refractory large B-cell lymphoma after treatment of relma-cel: 4-year follow-up in RELIANCE study.
Authors: Haiyan Yang, Ye Guo, Wenyu Li, Dehui Zou, Daobin Zhou, Zhao Wang, Mingzhi Zhang, Jianqiu Wu, Hui Liu, Zhen Xia, Su Yang, Zisong Zhou, Yun Qin, Yuqin Song, Jun Zhu
Journal: Journal of Clinical Oncology (2024)

e19001 Background: RELIANCE study (NCT04089215) demonstrated the efficacy and safety of relma-cel, a CD19-targeted chimeric antigen receptor T-cell product, in patients with heavily pre-treated relapsed/refractory large B-cell lymphoma (r/r LBCL). We previously reported efficacy of relma-cel, noting objective response rate (ORR) in 77.59% of patients (CRR 53.45%), 2-year progression-free survival (PFS) rate and overall survival (OS) rate were 38.8% and 69.3%, respectively. Herein, we aimed to update the long-term survival results for 4-year follow-up (FU). Methods: Study design was previously published. Eligible patients were adults with histologically confirmed r/r LBCL and had failed at least two prior lines of therapy, including an anti-CD20 monoclonal antibody and an anthracycline-based regimen. Patients were enrolled at 10 clinical sites in China and underwent lymphodepletion prior to receiving relma-cel at a single dose of 100 × 10 6 (n=27) or 150 × 10 6 (n=32) CAR+ T cells. The primary endpoint was ORR at 3-month, as assessed by investigators. Secondary endpoints were duration of response (DOR), PFS, OS and safety profiles. For this abstract, we collected the survival status and updated the survival outcomes. Results: From Nov 2017 to Dec 2019, a total of 68 patients were enrolled, and 59 received relma-cel infusion. Among 58 evaluable efficacy patients with 2-year FU, 31 achieved CR (CR group), 14 achieved PR (PR group) and 13 had no response (Non-responder group). As of Dec 18, 2023, with 48.1 months (95% CI, 37.75 to 49.38) of median FU, 25 patients were still alive, 18 were died (5 deaths in CR group, 5 in PR group and 8 in Non-responder group), and 15 patients were censored due to lost to FU including 7 lost within 2 years and 8 after 2 years. The median OS were not reached (NR), and 1-year and 2-year OS rate were reported previously. The update estimated landmark OS rates were 69.3% at 3-year and 66.7% at 4-year. The OS rates of CR group at each year were numerically higher than those of PR group and Non-responder group (87.1% v.s. 59.3% v.s. 30.8% at 3-year and 82.5% v.s. 59.3% v.s. 30.8% at 4-year; Table). Conclusions: Four-year FU results in RELIANCE Study suggested that, although heavily pretreated, the patients who had response, especially who achieved CR, may experience greater survival benefits, from relma-cel therapy. Clinical trial information: NCT04089215 . [Table: see text]