tbuckley/cabot-search huggingface dataset:
Bridging therapies used in trials testing CAR-T therapies.
Authors: Vinay Prasad, Victoria Kaestner, Alyson Haslam
Journal: Journal of Clinical Oncology (2024)

e19011 Background: Chimeric Antigen Receptor T-cell (CAR-T) therapy can induce durable remission in some patients but requires time for a patient’s own cells to be reengineered to produce CAR proteins that can bind to and destroy cancer cells. During this time, bridging therapy is often used in debulking to reduce treatment toxicities and to control the disease while waiting for the manufacturing of CAR-T cells. Because bridging therapy often involves systemic treatment, the bridging therapies can induce responses, in and of themselves, in clinical trials testing CAR-T therapies. As such, we sought to assess bridging therapies used in CAR-T trials. Methods: Using the FDA labels (labels.fda.gov) to identify the indications and the pivotal clinical trials that led to the approval of each CAR-T cell therapy, we looked at which bridging therapies were used, whether multiple therapies were combined, response rates, and the reported adverse events associated with bridging therapy. We took note of all relevant comments regarding bridging therapy in the main paper and supplemental results. Results: Of the 11 studies testing CAR-T therapies, 10 reported the bridging therapies that were used in the study. Notably, only three of 11 studies provided clear information about which combinations of bridging therapy treatments were used during the trials. Of those that reported the types of bridging therapies (n=10), the most commonly used bridging therapy was dexamethasone, which was used in every study (10/10). The next three most commonly used treatments include rituximab (6/10), gemcitabine (5/10), and etoposide (5/10). Of the trials, 2/11 clearly reported whether patients had a complete response (CR), partial response (PR), or very good partial response (VGPR) to bridging therapy. 5/11 vaguely reported responses, using terminology outside of CR, PR, VGPR. 4/11 trials did not report or mention any response information in regards to bridging therapy. Of all the trials, 1/11 clearly reported adverse events associated with bridging therapy in the supplement, while 10/11 of the trials listed adverse events associated with the treatment groups, without clarifying those associated with bridging. Conclusions: Although patients are often refractory to first-line therapies, which share considerable overlap with the bridging therapies used, these therapies may still induce responses. Despite this possibility, the reporting of bridging therapy combinations and their subsequent response rates and adverse event rates, is highly variable. Of 11 pivotal clinical trials that led to the approval of a CAR-T cell therapy, none clearly reported bridging therapy data that encompassed all three categories (combinations used, response rates, adverse events). What is more, these data were often omitted completely. These findings highlight the need for greater transparency in the reporting of bridging therapy in order to more reliably assess the efficacy of CAR-T therapies.
AB1658-PARE FEARS AND BELIEFS OF PATIENTS WITH RHEUMATOID ARTHRITIS AND SPONDYLOARTHRITIS UNDERGOING BIOTHERAPY: EVALUATION BY THE BMQ SCORE
Authors: F. E. Bennani, H. Bara, A. Mougui, I. El Bouchti
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are very common inflammatory rheumatisms. The advent of biological agents has significantly improved the prognosis of chronic inflammatory rheumatism (CIR). Furthermore, several beliefs regarding the risks associated with the use of these agents are expressed by patients. <h3>Objectives:</h3> The objective of this study was to evaluate the fears and beliefs of these patients undergoing biotherapy regarding their biological treatments. <h3>Methods:</h3> This is a cross-sectional and descriptive study, focusing on patients followed in our training for RA or severe AS, escaping traditional disease-modifying treatment or associated with a contraindication to it. The current treatment is biological (Anti TNF, Rituximab, Tocilizumab or Secukinumab). The questionnaire used to assess fears and beliefs: the specific BMQ (Belief in Medication Questionnaire). The specific BMQ questionnaire is made up of 2 parts: -The 1st part: 5 questions linked to the need for treatment -The 2nd part: 5 questions that assess concerns related to prescribing Each of the components is made up of 5 scales graduated from 1 (strong disagreement) to 5 (strong agreement). The specific BMQ is therefore rendered in the form of 2 scores ranging from 5 to 25. <h3>Results:</h3> In total, 61 patients were included (29 RA and 32 SPA), with an average age of 46.42 [18-72] years and a sex ratio of 1.03. Biotherapy was administered on average for 6.72 [1-14] years;24.59% were on Rituximab, 16.39% on Secukinumab, 6.56% on Tocilizumab and 52.46% on Anti-TNF.78% of patients consider biological treatment necessary while 22% report concerns.The median necessity score was 18.93 in patients followed for RA versus 18.5 in patients followed for SpA. The average concern score was 12 in RA patients versus 13.65 in SpA patients. Beliefs about the necessity of using biological treatment were more important than fear of this treatment among patients with a statistically significant difference (p=0.046). The statistical analysis of factors linked to beliefs under biological treatment showed greater beliefs about the necessity of treatment in very active RIC (p=0.024) and greater fear in the presence of adverse effects of biotherapy (p= 0.015). <h3>Conclusion:</h3> The majority of our patients had strong beliefs in their prescribed biological treatment, and few concerns about its long-term adverse effects. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1654-PARE DOES THE PERSPECTIVE OF SLE PATIENTS MATCH THE EXPERT OPINION AND DEFINITIONS OF REMISSION AND LOW DISEASE ACTIVITY STATE? PROSPECTIVE ANALYSIS OF 500 PATIENTS FROM A SPANISH MULTICENTER COHORT
Authors: C. Mouriño Rodríguez, J. M. Pego-Reigosa, Í. Rúa-Figueroa, F. Rubiño, I. Hernández-Rodríguez, R. Menor-Almagro, E. Uriarte Isacelaya, E. Tomero Muriel, T. C. Salman-Monte, I. Carrión Barberà, M. Galindo, E. Rodríguez Almaraz, N. Jiménez, L. Inês, A. Hernández, I. Altabás González
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> No data on agreement between patient perception, DORIS 2021 remission, LLDAS, or physician assessment is currently available. <h3>Objectives:</h3> The aim is to compare the SLE activity perceived by the patient using the Patient Acceptable Symptom State (PASS) question with the global assessment of activity by the physician, and the definitions of LLDAS/DORIS2021. <h3>Methods:</h3> A cross-sectional multicenter study involving SLE patients from seven Spanish Rheumatology Departments was conducted. The study applied DORIS 2021 remission criteria and LLDAS. Rheumatologists classified disease activity into five categories: remission, SACQ, low, moderate, or high. The patients were asked about their clinical SLE condition through the PASS question: "Considering all the different ways your disease is affecting you, if you were to stay in this state for the next few months, do you consider your current state satisfactory?": PASS yes/PASS no. Statistical analysis included descriptive cross-sectional analysis and Cohen's kappa for agreement analysis. <h3>Results:</h3> Among the 503 patients in the study (Table 1), 386 (77.4%) reported an acceptable symptom state according to the PASS question. Mean patient global assessment (PtGA) was 29.62 (±24.38) on a scale of 0-100, while mean physician global assessment (PGA) was 0.46 (±0.59) on a scale of 0-3. A total of 236 (47.6%) patients met DORIS 2021 remission criteria, and 289 (59%) met LLDAS. According to the rheumatologists' categorical classification, 435 (86.8%) patients were in remission or low disease activity (Table 2). Among PASS-affirmative patients, 65.5% met LLDAS and 57.9% met DORIS 2021 remission criteria, with lower PtGA (19.7) and PGA (0.29) scores. In the non-PASS group, 62.8% were not in LLDAS, and 87.6% did not meet DORIS 2021 remission criteria, with higher PtGA (58) and PGA (1) scores (Table 3). The overall agreement between PASS and categorical classification was 82% with a Cohen's kappa of 0.43. <h3>Conclusion:</h3> The majority of SLE patients reported an acceptable symptom state according to the PASS question, which aligns with the PtGA scale. Physicians' assessments also showed similarities with patient perspectives. However, notable differences were observed regarding remission/LLDAS criteria, indicating that while patient and physician perspectives align on subjective classification, variations exist concerning LLDAS and DORIS. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0935 AR882, A SELECTIVE URAT1 INHIBITOR, EXHIBITS NO DRUG-DRUG INTERACTIONS WITH KEY RENAL, HEPATIC, AND GI TRANSPORTERS
Authors: Z. Shen, R. Yan, E. Polvent, V. Hingorani, S. Yan, R. Keenan, L. T. Yeh
Journal: Annals of the Rheumatic Diseases (2024)
Efficacy and safety of mosunetuzumab-based regimens as first-line therapy in non-Hodgkin lymphomas: A systematic review of clinical trials.
Authors: Samer Jumean, Shatha Elemian, Wajeeha Aiman, Muhammad Ashar Ali, Amr Ramahi, Bader Al Omour, Hamid Salim Shaaban, Gunwant K. Guron, Munther Hammad, Michael Maroules
Journal: Journal of Clinical Oncology (2024)

e19013 Background: Bispecific antibodies (BsAbs) are emerging as a promising new immunotherapy modality in patients with lymphoma. Mosunetuzumab is a CD20xCD3 T-cell engaging bispecific monoclonal antibody that redirects T cells to eliminate malignant B cells, was first to receive approval for relapsed or refractory follicular lymphoma. Here, we report the safety and efficacy of Mosunetuzumab as a first line therapy in combination or monotherapy regimen in non-hodgkin lymphoma. Methods: A literature search was performed on PubMed with keywords for “Mosunetuzumab” AND “lymphoma”. The search was performed from the inception of data till 1/1/2024. A total of 237 articles were screened and three non-randomized clinical trials (nRCTs, N=124) were included. PRISMA guidelines were followed while conducting this systematic review. Results: In 3 clinical trials, 54 patients were treated with mosunetuzumab monotherapy, 40 with mosunetuzumab + cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and 30 with subcutaneous mosunetuzumab. 94 patients had diffuse large B-cell lymphoma (DLBCL), and 30 patients had follicular lymphoma. ORR, CR, and PR were reported in 56%, 43%, and 13% patients, respectively, treated with mosunetuzumab monotherapy in DLBCL. ORR, CR, and PR were reported in 87.5%, 85%, and 2.5% patients, respectively, treated with mosunetuzumab + CHOP in DLBCL. ORR, CR, and PR were reported in 96%, 83%, and 12.5% patients, respectively, treated with subcutaneous mosunetuzumab in follicular lymphoma. Neutropenia, thrombocytopenia, infections, and fatigue were common adverse effects given in the table. Conclusions: Mosunetuzumab with CHOP showed higher efficacy results and was well tolerated by most of the patients and can be an option to achieve high response rates in DLBCL. Subcutaneous mosunetuzumab was active in follicular lymphoma with manageable toxicity in follicular lymphoma. However, long-term results are needed to determine the durability of responses and long-term safety and survival rates with these regimens. [Table: see text]
A first-in-human phase 1, multicenter, open-label study of CB-012, a next-generation CRISPR-edited allogeneic anti-CLL-1 CAR-T cell therapy for adults with relapsed/refractory acute myeloid leukemia (AMpLify).
Authors: Naval Guastad Daver, Abhishek Maiti, David Andrew Sallman, Gail J. Roboz, Melhem M. Solh, Filippo Milano, Stephen Anthony Strickland, Alireza Eghtedar, Steven Brian Kanner, Guy Ledergor, Donna Marcy, Elizabeth Garner, Brian J. Francica, McKay Shaw, Kalin Bird, Jennifer Rattan, Enrique Zudaire, Socorro Portella, Pankit Vachhani, Jae H. Park
Journal: Journal of Clinical Oncology (2024)

TPS6586 Background: CAR-T cell therapies have shown significant clinical benefit in treating adults with many hematologic malignancies. In acute myeloid leukemia (AML), a challenge in the development of CAR-T cell therapies has been the limitation of suitable target antigens since many are also expressed on hematopoietic stem cells (HSCs). The target antigen C-type lectin-like molecule-1 (CLL-1) has emerged as an attractive therapeutic target due to its expression on AML mature blasts and leukemic stem cells and its absence on HSCs. CB-012 is an allogeneic CAR-T cell therapy that targets CLL-1. CB-012 is derived from healthy donor T cells by using Cas12a CRISPR hybrid RNA-DNA (chRDNA) technology to introduce 5 genome edits: (1) TRAC gene knockout (KO), which eliminates T cell receptor expression to reduce the risk of graft-versus-host disease, (2) site-directed insertion of a fully human anti-CLL-1 CAR into the TRAC locus, (3) KO of PD-1 to enhance antitumor activity by reducing T cell exhaustion, (4) β2-microgobulin ( B 2M) gene KO, which eliminates HLA class I presentation to mitigate host T cell-mediated rejection, and (5) site-directed insertion of a B2M–HLA-E-peptide fusion into the B 2M locus to reduce NK cell-mediated rejection. In murine xenograft models of AML, CB-012 significantly reduced the tumor burden and increased the survival of mice bearing CLL-1 + PD-L1 + tumors. Methods: CB-012 is being evaluated in a multicenter, Phase 1 clinical trial in patients with relapsed/refractory (r/r) AML. A 3+3 dose escalation design is being utilized with the primary objectives to determine the safety and tolerability of CB-012 and the recommended Phase 2 dose (RP2D). An expansion phase will follow dose escalation at the recommended dose(s) for expansion. Additional objectives include preliminary antitumor activity and pharmacokinetics. Key inclusion criteria include nonproliferative disease defined as ≤25% blasts in the bone marrow and peripheral blood, ECOG performance status ≤1, and adequate organ function. After receiving lymphodepletion therapy with cyclophosphamide (750 mg/m 2 /d) and fludarabine (30 mg/m 2 /d) administered concurrently for 3 days followed by a 2-day break, patients receive a single-dose infusion of CB-012 and are followed for safety and efficacy. The dose escalation portion of the study is actively enrolling patients. The AMpLify trial is registered at clinicaltrials.gov (NCT06128044). Clinical trial information: NCT06128044 .
Association between treatment (tx) response and PFS and OS in R/R chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL): A 12-month landmark (LM) meta-analysis.
Authors: Jennifer Ann Woyach, Xin Wang, Revathi Ananthakrishnan, San-San Ou, Serena K. Perna, Jacob Aptekar, Rahul Jain, Weixi Chen, Kayleen Ports, Paolo Ghia
Journal: Journal of Clinical Oncology (2024)

7047 Background: Despite advances in tx for CLL/SLL, CRs are rarely observed after tx in the R/R setting, thus impacting long-term outcomes. We evaluated the association between response after tx and survival outcomes in patients (pt) with R/R CLL/SLL. Methods: Adults with R/R CLL/SLL and ≥ 1 prior line of therapy (LOT) from 6 clinical trials (initiated after 01/01/2012 and completed before 12/31/2022) were sourced from the Medidata Enterprise Data Store. Cox models adjusted for potential prognostic factors were used to assess pt-level associations between achieving and maintaining a CR or CR with incomplete bone marrow recovery (CRi) by 12 mo after start of tx (LM date) and PFS and OS. In separate LM analyses (LMA), associations between achieving and maintaining CR/CRi, PR/nodular PR (nPR) by LM, or non-CR/non-PR (ie, those not achieving or maintaining CR/CRi or PR/nPR or not evaluated by LM), and PFS and OS were assessed. Results: Of 1604 pts (CLL, 97.7%; SLL, 2.3%; age ≥ 65 y, 61.8%; male, 66.6%; ECOG PS 0–1/2, 93.2%/6.8%; median [IQR] follow-up, 3.4 y [2.2–4.1]; median [IQR] LOT, 2 [1–3]; study tx, BTKi [40.4%], BCL2i [40.1%], anti-CD20 mAb [12.5%], and PI3Ki [9.9%]), 15.1% and 61.7% achieved a best overall response of CR/CRi and PR/nPR, respectively (ORR, 76.8%); 6.8% of pts had no response recorded in follow-up. A total of 1178 pts without progression, death, or censoring before LM were included in PFS LMA. Median (95% CI) PFS from LM was 64.4 mo (61.7–not reached [NR]) for CR/CRi, 43.3 mo (38.8–54.7) for PR/nPR, and 23.9 mo (18.3–50.6) for non-CR/non-PR. Pts who achieved and maintained CR/CRi had significantly longer PFS versus both non-CR/CRi and PR/nPR pts, with adjusted HR of 0.62 ( P = 0.01) and 0.64 ( P = 0.02), respectively (Table). For OS LMA, 1404 pts without death or censoring before LM were included. Median (95% CI) OS from LM was NR for CR/CRi and PR/nPR groups and 62.9 mo (51.2–NR) for non-CR/non-PR. At 24 mo from LM, 90% (85%–95%) CR/CRi, 87% (84%–89%) PR/nPR, and 72% (67%–77%) non-CR/non-PR pts were still alive. CR/CRi pts or PR/nPR pts had significantly longer PFS and OS versus non-CR/non-PR pts. Conclusions: We demonstrated that achieving and maintaining CR/CRi by 12 mo after start of tx was associated with significantly improved PFS versus achieving and maintaining PR/nPR, which was also better than not achieving/maintaining any response. These findings support the potential utility of durable CR/CRi as an informative early endpoint for assessing the value of tx in pts with R/R CLL/SLL. Adjusted HR (95% CI) [Table: see text]
AB1726 EFFICACY AND SAFETY OF RITUXIMAB IN ADULT PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS: A MONOCENTRIC COHORT STUDY
Authors: M. R. Pellico, M. Pandolfi, A. Amati, S. Germinario, C. Iannone, M. Cornalba, I. Pontikaki, A. Marino, S. Costi, M. Gattinara, R. F. Caporali, C. Chighizola
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Rituximab, a pharmacological agent targeting B cells, is commonly employed in the treatment of rheumatoid arthritis, while its efficacy and safety in juvenile idiopathic arthritis (JIA) patients remain scarcely documented. <h3>Objectives:</h3> This study aims at assessing the efficacy and safety of rituximab within a single-center cohort of adult JIA patients <h3>Methods:</h3> Patients were retrospectively recruited at the Rheumatology Transition Clinic of our institution in case of: i) a JIA diagnosis according to the International League of Associations for Rheumatology (ILAR) criteria [1], ii) age of at least 18 years, and iii) a minimum of 6 months of rituximab therapy Each course included two 1000 mg intravenous rituximab infusions 2 weeks apart, to be repeated based on clinical judgment every 24 weeks. <h3>Results:</h3> This study included 22 subjects (7 with oligoarticular (O-) JIA, 13 with polyarticular (P-) JIA, 2 with enthesitis-related arthritis [ERA]), whose demographics and clinical details are summarized in Table 1. All recruited patients had a recalcitrant disease, with a median of two failed biologics before starting rituximab. In 45% of cases, patients received rituximab in association with methotrexate. With rituximab, a similar improvement in DAS28 scores was observed across all JIA categories. In particular, after 12 months of rituximab therapy, remission was achieved by 86% of the patients, with a 100% remission rate in the O-JIA subgroup, 84% in patients with P-JIA and 50% in those with ERA. No significant differences in disease duration, age at JIA onset, age at start of rituximab, positivity for rheumatoid factor and/or antibodies against cyclic citrullinated peptides were observed between responders and non-responders. The overall median duration of treatment was 7.1 years, with a longer median retention in treatment in the O-JIA subgroup (9.71 years). Treatment with rituximab was complicated by seven major infections in the whole cohort, with only two patients requiring hospitalization because of lobar pneumonia and osteomyelitis due to Haemophilus influenzae. <h3>Conclusion:</h3> Rituximab allows controlling disease activity across different JIA categories, even in patients who have not responded to prior biological treatments. Rituximab demonstrates a tolerable safety profile. <h3>REFERENCES:</h3> [1] Petty RE, International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004;31:390–2. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1664-PARE THE SLEEP DISORDERS IN PSORIATIC ARTHRITIS
Authors: I. Elaroussi, S. Zniber, A. Mougui, E. B. Imane
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Psoriatic Arthritis (PsA) is classified in the group of spondyloarthritides, which can involve axial involvement, peripheral arthritis, enthesitis, psoriatic lesions, and, like all spondyloarthritides, uveitis or chronic inflammatory bowel diseases. It is a chronic inflammatory disease with highly variable presentation, leading to functional and psychological impairments, with a significant negative impact on the quality of life of patients, notably a marked deterioration in sleep quality. Therefore, understanding the patient's perception of their health is of fundamental importance to grasp the real impact of Psoriatic Arthritis. In this context, the European League Against Rheumatism (EULAR) has recently developed an instrument specifically assessing the impact of PsA on the patient (PsAID), comprising 12 items, including anxiety, sleep disturbances, and pain. <h3>Objectives:</h3> Our study aimed to assess the frequency of sleep disorders and explore their determinants in patients with psoriatic arthritis. <h3>Methods:</h3> A descriptive cross-sectional retrospective study including 90 patients meeting the Classification Criteria for Psoriatic Arthritis (CASPAR). Sleep was self-assessed using the numerical scale (0–10) 'sleep' from the PSAID-12 questionnaire. Sleep disorders were defined by a numerical scale ≥ 4. Demographic and clinical variables associated with sleep disorders were assessed through univariate analysis and Poisson regression to estimate the prevalence ratio (PR). <h3>Results:</h3> We included 90 patients with confirmed Psoriatic Arthritis (PsA). The mean age was 44.6 years [17-85], with a female predominance of 58.4%. The average disease duration was 5.42 years. Among our patients, 4.4% were on biologic therapy, 36.7% had psoriasis covering less than 5% of body surface area, and 2.2% had a family history of psoriasis. The median self-reported sleep quality score was 6 (2–9), with 88.9% of our patients experiencing sleep disorders. In the Poisson regression model, patient-reported anxiety (PR: 1.11 [1.03–1.20], p &lt; 0.001) was significantly associated with sleep disorders. <h3>Conclusion:</h3> Sleep quality is a domain often overlooked despite significant degradation observed in patients with Psoriatic Arthritis (PsA). Sleep disorders were present in 88% of patients in our study. Unlike inflammation, pain, and anxiety were associated with sleep difficulties. We believe it is important to establish a systematic assessment of sleep quality, and further studies will be necessary to identify therapeutic strategies capable of improving the sleep of patients with Psoriatic Arthritis. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>