tbuckley/cabot-search huggingface dataset:
Combination of pirtobrutinib and lentiviral transduced bispecific anti-CD20/CD19 (LV20.19) CAR T-cell therapy to improve outcomes in patients with relapsed/refractory lymphoma.
Authors: Fateeha Furqan, Katie Palen, Bryon Johnson, Tyce Kearl, Peiman Hematti, Walter L. Longo, Mehdi Hamadani, Timothy S. Fenske, Nirav Niranjan Shah
Journal: Journal of Clinical Oncology (2024)

7043 Background: Combination trials of BTK inhibitors (BTKi) with CAR-T have suggested potential synergistic benefit by improving CAR-T immunophenotype and clinical outcomes but are limited by increased toxicity. We report immunophenotype, cytokine profile, and patient outcomes with the new non-covalent BTKi, pirtobrutinib (pirto) when given prior to LV20.19 CAR-T and compare the final CAR product to pts who did not receive pirtobrutinib prior to CAR. Methods: Pts received LV20.19 CAR-T as part of a phase 1/2 trial (NCT04186520). Only pts who received pirto £4 weeks prior to apheresis were included. To determine the impact of pirto on LV20.19 CAR-T, we calculated both polyfunctionality (PFA) and polyfunctional strength index (PSI) for each product using the Isoplexis. Descriptive statistics, t-tests and Kaplan-Meier method were used as appropriate. Results: 11 pts received pirto prior to LV20.19 CAR-T (Table). Median age was 65 (50-80) yrs and median prior lines of therapy were 4 (2-8). There were 4 MCL pts, 5 Richter’s (RT)/CLL, 1 MZL and 1 DLBCL. Median duration of pirto was 4 (1-20) mo. Pts were on pirto for a median of 12 (1-22) days prior to apheresis. All except 1 pts received target CAR-T dose. The day 28 ORR was 82% (CR=7, PR=2). After a median follow up of 13 mo, 3 pts died (PD, Covid, Guillain Barre). The median PFS and OS were both 30.8 mo while the 1-year PFS and OS rates were 9 and 15 mo respectively. 9 pts had CRS and 2 had ICANS, all grades 1-2, while 4 had IEC-HS. One pt had afib recurrence and 1 pt had CMV viremia within 30 days of CAR-T. Among the pts with immunophenotypic data (n=10), there were no differences in naïve or more differentiated T-cell percentages in apheresis and final CAR-T products when compared to pts who did not receive pirto before LV20.19 CAR-T (n=57). Although not statistically significant, both PFA (CD4=61.8 vs 59, CD8= 49.8 vs 46.9) and PSI (CD4= 1752 vs 1608, CD8=1299 vs 1079) were higher with pirto pre-treated pts, suggesting a potential trend towards improved CAR-T functionality. Conclusions: These data represent the largest experience of pirto prior to CAR-T apheresis and demonstrate that pirto can be safely used as a bridge to LV20.19 CAR-T without negatively impacting their immunophenotype and potentially improving functionality. These data support our planned phase 1 clinical trial to assess the safety of pirto as bridging and maintenance therapy with LV20.19 CAR-T (NCT05990465). [Table: see text]
POS0924 CLUSTER ANALYSIS FOR IDENTIFICATION OF CLINICAL PHENOTYPES IN BEHÇET’S DISEASE IN A COHORT FROM NORTHERN SPAIN
Authors: J. L. Martín-Varillas, L. Sanchez-Bilbao, R. Fernández Ramón, C. Álvarez-Reguera, A. Serrano-Combarro, R. Gálvez-Sánchez, E. Aurrecoechea, R. Blanco
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Behçet's disease (BD) is characterized by heterogeneity of clinical manifestations due to involvement of variable blood vessels. <h3>Objectives:</h3> to identify clinical phenotypes using cluster analysis. <h3>Methods:</h3> a model-based clustering relaying on 16 clinical variables was performed in a retrospective cohort of 120 BD patients, diagnosed and follow-up from January 1, 1980 to December 31, 2019 in 3 hospital at Northern Spain (Cantabria). Chi-square test and ANOVA were used to compare categorical and continuous variables among groups. Two-sample t-tests and the partition of Pearson's chi-square statistic were used in pairwise comparisons. <h3>Results:</h3> Four groups were identified in this study: C1 (n=47; 39.2%), C2 (n=33; 27.5%), C3 (n=33; 27.5%) and C4 (n=7; 5.8%). The clusters were defined as follows: C1 as mucosal involvement, C2 as joint involvement and pseudofolliculitis, C3 as neurological and vascular involvement and C4 as uveitis and erythema nodosum. No baseline demographic differences between clusters and no differences in the application of classification criteria were observed (<b>Table 1</b>). Oral ulcers were predominant in all clusters, ranging from 85.7% (C4) to 95-97% (C1-C2), with no significant differences. However, a higher frequency of genital ulcers was observed in C1 compared to the other clusters. Similarly, a significantly higher frequency of erythema nodosum was observed in C4 (85.7%) and of pseudofolliculitis in C2 (93.9%) (p&lt;0.001). In addition, arterial involvement was more prevalent in C4 (100%, p&lt;0.001) but there were no differences in venous thrombotic involvement. Aneurysms were only observed in C4 (<b>Figure 1</b>). <h3>Conclusion:</h3> we have defined 4 BD phenotypes in our study. This cluster approach may be useful for better patient management due to early identification of clinical patterns. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1649-PARE BARRIERS TO DIAGNOSIS, TREATMENT, AND CARE FOR IgG4-RELATED DISEASE: DATA FROM A LARGE COHORT OF ITALIAN PATIENTS
Authors: K. Gavigan, M. Picone, I. Galetti, L. Dougherty, A. Cordova, E. Rivera, E. Stone, S. Venkatachalam, J. H. Stone, E. Della Torre
Journal: Annals of the Rheumatic Diseases (2024)
POS1203 PSORIATIC ARTHRITIS, SERONEGATIVE RHEUMATOID ARTHRITIS, AND SEROPOSITIVE RHEUMATOID ARTHRITIS: CIRCULATING IMMUNE CELL AND CYTOKINE PHENOTYPIC PROFILES
Authors: B. C. Li, Q. L. Guo, R. Su, C. Wang
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Immunological dysregulation constitutes the primary pathogenic mechanism in Psoriatic Arthritis (PsA) and Rheumatoid Arthritis (RA). However, these conditions exhibit distinct differences at the histopathological and clinical levels. A specific subset within RA, known as Seronegative Rheumatoid Arthritis (SnRA), shares similarities with PsA, posing challenges for clinical differentiation. <h3>Objectives:</h3> This study aims to investigate the peripheral blood lymphocyte subsets, CD4+ T cell distribution characteristics, and differential expression of cytokines in patients with PsA, SnRA, and SpRA. <h3>Methods:</h3> A total of 78 patients with PsA, 41 patients with SnRA, and 79 patients with SpRA who sought medical attention at the Rheumatology and Immunology Department of Shanxi Medical University Second Hospital from January 2020 to October 2020 were included in this study. General clinical data were collected, and peripheral blood lymphocyte subsets (T cells, B cells, CD4+ T cells, CD8+ T cells, NK cells), CD4+ T cell subsets (Th1 cells, Th2 cells, Th17 cells, Treg cells), and serum levels of cytokines (IL-2, IL-4, IL-6, IL-10, INF-γ, TNF-α) were measured using flow cytometry and CBA, respectively. <h3>Results:</h3> (1) PsA exhibited varying degrees of elevation in peripheral blood T cell count, B cell count, CD4+ T cell count, CD8+ T cell count, and Th2 cell count compared to SnRA and SpRA (Figure 1A); (2) SpRA patients showed significantly higher levels of various cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, INF-γ, TNF-α) compared to both SnRA and PsA, with no significant differences observed between PsA and SnRA in cytokine levels (Figure 1B); (3) SpRA patients exhibited elevated Th1/Th2 and Th17/Treg ratios compared to the other two groups (Figure 2A); (4) Principal Component Analysis (PCA) of lymphocyte subset ratios (CD4+ T/CD8+ T, Th1/Th2, Th17/Treg) and cytokine levels (IL-2, IL-4, IL-6, IL-10, IL-17, INF-γ, TNF-α) revealed strikingly similar overall distribution characteristics in lymphocyte subset ratios and cytokine levels between PsA and SnRA patients (Figure 2B). <h3>Conclusion:</h3> In comparison to PsA and SnRA, patients with SpRA exhibit more severe immunological dysregulation and higher levels of inflammatory cytokines. Additionally, the overall distribution characteristics of lymphocyte subset ratios and cytokine levels are similar between PsA and SnRA patients, providing immunological evidence for the clinical and pathological similarities between these two diseases. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
Evaluating CR as a surrogate endpoint for PFS in R/R chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): A meta-analysis of randomized controlled trials (RCT).
Authors: Lin Wang, Tim Disher, Fei Fei Liu, Murat Kurt, Serena K. Perna, Elise Aronitz, Toby A. Eyre, Matthew Steven Davids
Journal: Journal of Clinical Oncology (2024)

7046 Background: CLL/SLL is the most common leukemia in adults. Achieving a CR by International Workshop on CLL 2018 criteria indicates complete eradication of CLL/SLL in all disease compartments. Patients with R/R CLL/SLL who achieved CR tend to have delayed disease progression/death compared with patients who did not achieve CR. This is the first report to evaluate CR as a surrogate endpoint for PFS in R/R CLL/SLL using aggregate RCT data. Methods: A systematic literature review (SLR) identified published RCTs in R/R CLL/SLL from inception to 10/2023, reporting nonzero CR rates (CRR) and PFS. Association between treatment effects on CR and PFS across RCTs was estimated using a weighted linear model (WLM) in the primary analysis, and Daniels and Hughes (D&amp;H) and Riley bivariate random-effects meta-analysis (BRMA) in sensitivity analyses. Strength of association was assessed based on surrogacy criteria described by D&amp;H. Predictive performance of models was evaluated using leave-one-out cross-validation. Results: The SLR identified 13 RCTs with a total of 4388 patients with R/R CLL/SLL treated with a variety of therapies, including but not limited to BTKi, BCL2i, PI3Ki, CAR T cell therapy, anti-CD20 mAb, and chemotherapy. Across the evidence base, CRR ranged from 0.48% to 38.10% and median PFS was between 1 and 35.9 months (excluding unreached medians). Across RCTs, contrasting treatment and control arms, higher odds of CR resulted in lower hazards of disease progression/death (CRR improvement translated to PFS benefit). D&amp;H surrogacy criteria were met for WLM: 1) a near-zero, statistically nonsignificant intercept, indicating that no treatment effect on CRR implies no effect on PFS; 2) a negative, statistically significant slope, suggesting that improved CRR correlates with longer PFS; and 3) a near-zero conditional variance, meaning that PFS HR variation was primarily explained by CR odds ratio. During cross-validation, treatment effects on CR were predictive of PFS benefits, as the 95% predictive interval of PFS HR contained the observed HR in all RCTs for WLM. Results were largely consistent across all 3 models(Table). Conclusions: Improved CRR corresponds to prolonged PFS across RCTs and treatment comparisons. The results support CRR as an important treatment goal for R/R CLL/SLL and a valid surrogate endpoint. Consistent results and predictive performance across different models indicate the robustness of the results. [Table: see text]
Factors associated with manufacturing failure of commercial CD19 CAR-T cell products for large b cell lymphoma (LBCL).
Authors: Romil Patel, Ashwath Gurumurthi, Lei Feng, Jason Westin, Loretta J. Nastoupil, Ranjit Nair, Swaminathan P Iyer, Janet M. Torres, Yago Nieto, Partow Kebriaei, Misha Hawkins, Dai Chihara, Luis Malpica, Sherry Adkins, Elizabeth J. Shpall, Jeremy L Ramdial, Paolo Strati, Chitra M. Hosing, Sattva Swarup Neelapu, Sairah Ahmed
Journal: Journal of Clinical Oncology (2024)

7044 Background: As CD19 chimeric antigen receptor T-cell (CAR-T) therapy has shown curative potential in patients (pts) with relapsed/refractory (R/R) LBCL, indications for treatment are expanding. The reported manufacturing failure rate was 1-13% in clinical trials, but there is poor understanding of out-of-specification (OOS) products and CAR-T products on 2nd apheresis. This study aims to characterize factors associated with successful manufacturing. Methods: This study includes pts with R/R LBCL who underwent apheresis for CAR-T product between 12/2017 and 2/2023. Baseline variables were obtained at time of apheresis. OOS product is defined as not meeting eligibility for a commercial product but suitable for infusion on expanded access protocol. 2nd apheresis was performed due to initial manufacture failure. Progression-free survival (PFS) is the time from CAR-T conditioning to disease progression or death, whichever occurs first. Overall survival (OS) is defined as time from conditioning to death or last follow-up. A chi-square test or Fisher’s exact test was used for comparison of 2 categorical variables. Results: 319 pts underwent apheresis; 261(78%) were axicabtagene ciloleucel, 26(8%) were tisagenlecleucel and 47(14%) were lisocabtagene maraleucel 284(85%); products were in-specification (in-spec) on 1st apheresis, 8(2%) in-spec on 2nd apheresis, 27(8%) OOS, and 15(4%) manufacturing failures. Comparison of variables are in the table. OOS rates were 10/250(4%) for axicabtagene, 4/23(17.4%) for tisagenlecleucel and 13/46(28.3%) for lisocabtagene. Reason for OOS product were low viability:14, high interferon:4, internal manufacturing issue:2, CD4 lineage purity:2, high transduction:1, low transduction:2, and low vector copies:2. No association was found with clinical factors and OOS. Factors associated with OOS were advanced stage (P=0.012), IPI score &gt;3 (p=0.001), extranodal involvement (P=0.012) and older age (p= 0.002). In-spec product on 1st apheresis had greater OS (p= 0.011) and PFS (p=0.043) than 2nd apheresis. Conclusions: Factors predictive of OOS product include older age, advanced disease, extranodal involvement and high IPI. Pts requiring 2nd apheresis had worse survival. Lisocabtagene had higher likelihood for OOS product. Outcomes for OOS products are not well described. Failure to manufacture an eligible product is a barrier for LBCL pts to receive CAR-T therapy. [Table: see text]
AB1651-PARE EFFECT OF THERAPEUTIC PATIENT EDUCATION ON COMPLIANCE WITH BIPHOSPHONATES IN OSTEOPOROSIS
Authors: A. Mghiouach, K. Nassar, N. Tamir, F. A. Aznag, J. Daoudim, S. Sboul, N. E. H. Amine, S. Zaher, A. Ajerouassi, S. Janani
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Therapeutic education plays an important role in improving the management of osteoporosis (OP). The main targets of therapeutic education in osteoporosis are understanding of the disease, adherence to treatment, optimal calcium intake, physical activity and prevention of the risk of falls. <h3>Objectives:</h3> evaluate the therapeutic adherence of patients followed in bone consultation for osteoporosis after therapeutic education <h3>Methods:</h3> A survey after 12 therapeutic education sessions carried out over a 3-month period (from August 2023 to November 2023) at the CHU IBN ROCHD rheumatology department; each session included 10 patients receiving therapeutic education. Inclusion criteria: patients followed at the fragile osteopathy unit for osteoporosis or osteopenia. The questionnaire included a section on patients' satisfaction with their reception, the explanations and messages delivered by the educational team, the contribution of new knowledge on osteoporosis and osteopenia, and the application of the recommendations explained by the educational team in daily life. <h3>Results:</h3> 120 patients completed the questionnaire, with a sex ratio of 0.09 (91.6% women and 8.3% men). The average duration of the disease was 3 years. All patients were very satisfied with the welcome, explanations and messages delivered by the educational team. The methods used were judged to be very clear by 95% of patients. A one hour session is estimated sufficient for all patients. All patients felt that the recommendations on the importance of treatment compliance were important; all our patients felt that they had received new messages on osteoporosis. 90% of patients changed the idea that treatment should provide a momentary benefit and should relieve pain, and 40% learned that the duration of treatment is prolonged and should not stop after 3 or 6 months. <h3>Conclusion:</h3> therapeutic education seems to have very good results, improving knowledge of osteoporosis and increasing adherence to treatment. In our study, we observed a very good improvement in our patients' compliance with treatment. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1708 LONG-TERM EFFICACY OF ETANERCEPT AND ADALIMUMAB IN A COHORT OF PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS
Authors: A. Amati, S. Germinario, S. Costi, C. Iannone, M. R. Pellico, M. Pandolfi, A. Marino, C. Chighizola, R. F. Caporali
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Biologic drugs (bDMARDs) have dramatically changed the disease course in juvenile idiopathic arthritis (JIA). However, scarce evidence about their long-term efficacy and safety is available. <h3>Objectives:</h3> The aim of this study is to illustrate the long-term efficacy and safety of etanercept (ETN) and adalimumab (ADA) as first-line therapy in a monocentric cohort of JIA patients. <h3>Methods:</h3> Clinical data of patients with long-term AIG treated with ETN or ADA were retrospectively collected. The retention rate of the two bDMARDs was estimated by the Kaplan-Meier method. <h3>Results:</h3> Of the 118 patients included (72% female), 58 were treated with ETN and 60 with ADA. The most common diagnosis was oligoarticular JIA (55%), followed by polyarticular JIA (30%). The median age at disease onset was 3 years (1-7), with a median follow-up of 14 years. The median time to referral was 2 months (1-5 months). The median duration of treatment was 61.5 months for ETN and 49.5 months for ADA. At 1 year of treatment, the retention rate was 85% in patients treated with ADA and 91% in case of ETN therapy, at 2 years it was 70% in ADA and 73% in ETN, at 5 years it was 31% in ADA and 50% in ETN. In 62 cases (52%), bDMARD treatment was discontinued due to: sustained remission (17%; 4 in ADA group and 7 in ETN group), secondary non-response (19%; 4 in ADA and 8 in ETN), active uveitis (27%; 9 in ADA group and 8 in ETN group), while 19% of patients discontinued first-line bDMARD due to occurrence of adverse events (3 in ADA group and 9 in ETN), such as gastro-intestinal side effects (n=1 ADA, n=2 ETN) and development of anxious-depressive symptoms (n=2 ADA, n=1 ETN). Recurrent infectious events (n 3), occurrence of allergic reactions (n 2) and elevation of liver function tests (n 1) appeared more frequently in the ETN population. At the last follow-up, 44% of patients in ADA and 39% of patients in ETN were on methotrexate or leflunomide in combination with bDMARD. 85.9% of patients had achieved sustained clinical remission. <h3>Conclusion:</h3> Long-term treatment with ETN and ADA has been shown to be effective and safe for patients with JIA, as evidenced by the high retention rate recorded in our cohort. Most patients maintain current therapy for years to preserve remission status. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS0546 SAFETY AND EFFICACY OF ANIFROLUMAB IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) WITH MINOR FLARES AFTER ACHIEVING THE LUPUS LOW DISEASE ACTIVITY STATE (LLDAS) IN REAL-WORLD CLINICAL PRACTICE:LOOPS REGISTRY
Authors: Y. Miyazaki, S. Nakayamada, S. Kubo, S. Matsunaga, H. Tanaka, K. Hanami, S. Fukuyo, Y. Satoh-Kanda, Y. Inoue, Y. Todoroki, M. Ueno, Y. Tanaka
Journal: Annals of the Rheumatic Diseases (2024)
Survival outcomes after autologous stem cell transplantation in T follicular helper type lymphoma.
Authors: Anath Christopher Lionel, Alexandra Elias, Rishab Prakash, Francisco Vega, Keyur P. Patel, Chitra M. Hosing, Luis Malpica, Ranjit Nair, Samer Ali Srour, Swaminathan Padmanabhan Iyer
Journal: Journal of Clinical Oncology (2024)

7073 Background: T follicular helper (TfH)-type lymphoma is the most common subtype of peripheral T-cell lymphoma (PTCL). TfH lymphoma consists of angioimmunoblastic T-cell lymphoma (AITL), PTCL-TfH and Follicular T cell lymphoma. Most patients receive first-line treatment with anthracycline-based chemotherapy regimens with a potential role for consolidation with autologous stem cell transplantation (ASCT). In this study we analyzed survival outcomes in TfH lymphoma. Methods: This is an IRB approved retrospective analysis of patients with TfH lymphoma followed between 1997–2023 at the MD Anderson Cancer Center. Demographics, treatment history, response and survival outcomes were collected and analyzed. Next-generation sequencing (NGS) data was collected from a panel of 162 cancer-related genes. Survival analysis was performed with Kaplan Meier curves and comparisons were made with log-rank tests. Results: Of the 218 patients with TfH lymphoma for whom information was known about prior history of ASCT, 84 (39%) underwent ASCT (Table). At the time of diagnosis, the majority of patients had advanced stage disease (92% with stage III or IV) and elevated LDH (89%). NGS testing was available from 31 patients and the genes with recurrent somatic mutations identified were TET2 (65% patients), DNMT3A (29%), RHOA (13%), IDH2 (10%), PLCG1 (10%), TP53 (10%), ATM (6%), CCR7 (6%), JAK3 (6%) and STAT3 (6%). The three most common first-line treatments were CHOP (37%) followed by CHOEP (14%) and combination of brentuximab with either CHP or CHEP (13%). Patients who received ASCT were significantly younger (Table). The median overall survival (OS) for the cohort was 40.3 months with median progression-free survival (PFS) after first treatment of 12.5 months. Patients who received ASCT had a significantly higher overall survival (log-rank test p-value &lt; 0.01) compared to those who did not receive ASCT. Conclusions: This retrospective analysis of a large single institution cohort of patients with TfH lymphoma found significantly improved OS in those who underwent ASCT compared to those who did not. Given the sizeable proportion of patients who are transplant-ineligible due to age or comorbidities, there is a need for newer consolidation approaches for TfH lymphoma. [Table: see text]