tbuckley/cabot-search huggingface dataset:
Flat dose intravenous immunoglobulin (IVIG) for primary infection prophylaxis after CAR-T for B-cell non-Hodgkin lymphoma (B-NHL).
Authors: Spencer Lessans, Morgan Zenner, Bhagirathbhai R. Dholaria, Adetola Kassim, Reena Jayani, Eden Biltibo, Shakthi Bhaskar, David S. Morgan, Bipin N. Savani, Olalekan O. Oluwole, Muhamed Baljevic, Vivek Patel
Journal: Journal of Clinical Oncology (2024)

e19004 Background: Prolonged hypogammaglobulinemia is a common side effect of CD19 chimeric antigen receptor (CAR) T-cell therapy for B-NHL. Average infection rates 1 year (yr) post CAR-T are 44-53% (Kampouri, Tran Infect Dis 2023). Prophylactic IVIG is typically dosed by weight; however, optimal dosing strategy remains unknown. We explored the efficacy of reduced flat IVIG dose on infection rates and non-relapse mortality (NRM) post CAR-T. Methods: B-NHL pts who received commercial CD19 CAR-T therapy from Nov 2017 to Mar 2023 at Vanderbilt Medical Center were included. All pts were on trimethoprim-sulfamethoxazole and valacyclovir for prophylaxis. IVIG at a flat dose of 10 grams was given for IgG &lt; 400 mg/dL. Relevant clinical variables were collected from day 30 to 1 yr. Infections were defined as mild (treated outpatient), moderate (required admission), or severe (required intensive care unit) and by CTCAE v5 criteria. Severe neutropenia was defined as ANC&lt;500 and severe lymphopenia was ALC&lt;500. NRM was defined by death without progression or relapse. Estimated cost of therapy was $140/gram of IVIG based on previously published data. Results: A total of 43 pts (35 large cell lymphoma, 7 mantle cell lymphoma, and 1 follicular lymphoma) with median follow up of 445 days (range 134-2141) were included. Axicabtagene ciloleucel was given to 34 pts (79%), tisagenlecleucel to 2 pts (5%), and brexucabtagene autoleucel to 7 pts (16%). Median age was 58 (range 22-81). Median number of pre CAR-T therapies was 3 (range 1-7). There were 52 total infections with median time to first infection of 165 days (range 31-365). Of all infections, 21 (40%) were viral, 29 (56%) bacterial, and 2 (4%) fungal. There were 31 (60%) mild infections, 19 (36%) moderate, and 2 (4%) severe. Multiple G≥3 infections occurred in 14 pts (33%). At first infection, 4 pts (10%) had severeneutropenia and 13 pts (31%) had severelymphopenia. IVIG was given to 27 pts (63%). Median IgG at D30 was 438 mg/dL (range 143–1099) and 414 mg/dL (range 133–842) at D60. Prolonged IgG≤400 at 6 months occurred in 15 pts (35%). Median IVIG cost using flat dosing was $2800 (range $0-12,600) compared to a median cost of $8,075 (range $0-76,642) if weight-based dosing was utilized. NRM was 9% (4 pts). Of those pts, only 1 had a G≥3 infection during the first-year post CAR-T. Conclusions: We demonstrate comparable infection rates 1 yr post CD19 CAR-T and low NRM with the use of 10g flat IVIG dosing for consecutively treated pts. In addition, only 1 of 4 pts with NRM had severe infection within 1 yr. Notably, 35% of pts had persistent hypogammaglobulinemia at 6 mo and use of a flat dosing schedule provided substantial cost reduction. These findings should be validated in a prospective randomized trial.
Frontline treatment with zanubrutinib plus rituximab (ZR) followed by short course R-DHAOx in patients with mantle cell lymphoma (MCL): Results of the phase II CHESS clinical trial.
Authors: Qingqing Cai, Yi Xia, Huiqiang Huang, Zhiming Li, He Huang, Guowei Li, Yuchen Zhang, Yi Cao, Yan Gao, PanPan Liu, Xiaojie Fang, Man Mie, Xiaopeng Tian, Xiuhua Sun, Xueyi Pan
Journal: Journal of Clinical Oncology (2024)

7062 Background: Combining Bruton’s tyrosine kinase (BTK) inhibitor and rituximab showed favourable efficacy as first-line therapy for mantle cell lymphoma (MCL). Zanubrutinib, a next-generation, highly-selective BTK inhibitor, achieved promising antitumor activity in MCL. In this multicenter phase II trial (CHESS - chemo-less), we aimed to investigate the efficacy and toxicity of zanubrutinib plus rituximab (ZR) combination, followed by short course cytarabine-based chemotherapy, then zanubrutinib maintenance as frontline therapy for MCL (NCT04624958). Methods: Previously untreated MCL patients enrolled and received induction therapy of ZR until complete response (CR) or to a maximum of 12 cycles, and followed by 4 cycles of R-DHAOx regimen (rituximab, dexamethasone, cytarabine and oxaliplatin). Patients achieving CR after chemotherapy would receive maintenance therapy with zanubrutinib for a maximum of 1 year. The primary endpoint was CR rate after induction therapy with ZR regimen. Minimal residual disease (MRD) of bone marrow and peripheral blood were evaluated by flow cytometry. Results: From Oct 2020 to Nov 2023, a total of 42 patients were enrolled and the enrollment was finished. The median age was 57 years (IQR, 51-64). Stage III-IV accounted for 92.8%, and 42.8% were intermediate or high risk simplified MIPI. Thirty-four patients (81.0%) were classic histological subtype. The median cycle of ZR was 4 (range, 2-6). As of Jan 2024, among 37/42 patients with post-treatment PET evaluation, the best CR rate of ZR regimen was 91.9% (34/37), and 94.1% (32/34) obtained CR after 2-4 cycles. The bone marrow MRD negative CR rate was 92.0% (23/25). The other 5/42 patients were still receiving ZR treatment, and PET evaluation would be performed subsequently. Among 27 patients who finished chemotherapy and were evaluable for response, only one patient experienced disease progression. With a median follow up of 11.6 months, the 1-year progression-free survival and overall survival was 90.1% and 96.7%, respectively. Two patients died due to lymphoma (n=1) and COVID-19 (n=1). Grade 3-4 adverse events on ZR regimen were neutropenia (n=3), fatigue (n=2), and aminotransferase (n=1). During chemotherapy, grade 3-4 thrombocytopenia was observed in 75.8% of patients. Conclusions: Induction treatment with ZR followed by short-course R-DHAOx chemotherapy yielded promising antitumor efficacy. This strategy might reduce the toxicity of cytarabine-based chemotherapy without weakening the therapeutic efficacy. Clinical trial information: NCT04624958 . [Table: see text]
POS0575 COVID-19 IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH TOFACITINIB: A RETROSPECTIVE CLINICAL STUDY
Authors: Y. Liu, D. Huang
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> While tofacitinib are important for controlling rheumatoid arthritis (RA) disease activity, their influence on SARS-CoV-2 infected in people with RA remains unclear. This uncertainty has led to anxiety, social isolation due to shielding practices and tofacitinib discontinuation, which may contribute to RA flares. The goal of this study is to assess the safety of tofacitinib in patients with RA who also have concurrent coronavirus disease-19(COVID-19) infection. <h3>Objectives:</h3> To characterize the clinical outcomes of tofacitinib with the COVID-19 severity in rheumatoid arthritis, and to investigate the safety of using tofacitinib in patients with RA)during the COVID-19 pandemic. <h3>Methods:</h3> We designed a retrospective monocentric prevalence study, recording the personal and clinical data of RA patients who received Tofacitinib and their cohabitants, with focus on the presentation of signs and symptoms related to COVID-19. The statistical methods were used for comparative analysis. <h3>Results:</h3> The study enrolled a total of 115 RA patients and 236 cohabitants, 83(72.2%) RA patients and 179(75.8%) cohabiters had been infected or high suspicion infected with SARS-COV-2, and the difference was not statistically significant. Compared with their cohabitating, Tofacitinib users had a lower incidence of fever(p=0.002) and cough(p=0.015), and lower maximum body temperatures(p&lt;0.001). In COVID-19 cases, RA patients tend to stop Tofacitinib from the first day of symptom onset, but withdraw of Tofacitinib does not affect the RA progressive and COVID-19 hospital admission rate. <h3>Conclusion:</h3> RA patients using Tofacitinib did not increase the susceptibility to COVID-19, and could partly reduce the COVID-19 symptoms. Continued use of tofacitinib during COVID-19 infection does not increase the incidence of COVID-19 symptoms or hospitalization rates, and may even alleviate them to some extent. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
A novel and selective oral PI3Kα/δ inhibitor, TQ-B3525, in patients with relapsed and/or refractory follicular lymphoma: A phase II, single-arm, open-label study.
Authors: Huaqing Wang, Aibin Liang, Jifeng Feng, YANYAN LIU, Zhengzi Qian, Da Gao, Xuehong Ran, Hui Zhou, Lihong Liu, Binghua Wang, Meiyun Fang, Hebing Zhou, Zhenqian Huang, Shi Tao, Zhuowen Chen, Liping Su, Hang Su, Yu Yang, Xiaobao Xie, Zhiming Li
Journal: Journal of Clinical Oncology (2024)

7057 Background: TQ-B3525 is a novel and selective oral PI3K α/δ inhibitor. In an earlier Phase I trial, TQ-B3525 achieved outstanding efficacy in subjects with refractory/relapsed follicular lymphoma (R/R FL) (2020 ASCO Abstract #8058). Here, we report the result from a single-arm, open-label, phase II registration study evaluating the safety and efficacy of TQ-B3525 in R/R FL patients. Methods: This phase II study included exploratory stage 1 and confirmatory stage 2. Patients with R/R FL after ≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until disease progression or intolerable toxicity. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR). Secondary endpoints were ORR by investigator assessment; the IRC- and investigator-assessed disease control rate (DCR), time to response (TTR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: Based on results (ORR, 88.0%; DOR, 11.8 months; PFS, 12.0 months) in 25 patients at stage 1, second stage study was initiated and included 82 patients for efficacy/safety analysis.Patients received a median of 3 prior lines, with 56.1% refractory to previous therapies; 73.2% experienced POD24 at baseline. At stage 2, ORR was 86.6% (71/82; 95% CI, 77.3%-93.1%), with 28 (34.2%) complete responses. Seven (8.5%) had stable disease for DCR of 95.1%. Median TTR was 1.8 months. Among 71 responders, median DOR was not reached; 18-month DOR rate was 51.6%. At median follow-up of 13.3 months, median PFS was 18.5 (95% CI, 10.2-not estimable) months; estimated 24-month OS rate was 86.1%. Response rates and survival data were consistent across all subgroups. Grade 3 or higher treatment-related adverse events occurred in 63 (76.8%) patients, with neutrophil count decreased (22.0%), hyperglycemia (19.5%), and diarrhea (13.4%) being common. Conclusions: TQ-B3525 exhibited favorable efficacy and manageable safety profiles, supporting its potential as a valuable treatment modality for heavily pretreated Chinese R/R/ FL patients. Clinical trial information: NCT04324879 . [Table: see text]
Non-Hodgkin lymphoma mortality disparities across different sexes, races, and geographic locations.
Authors: Jia Yi Tan, Yong Hao Yeo, Aharnish Patel, Kok Hoe Chan, Mohammad Muhsin Chisti, Daniel Ezekwudo
Journal: Journal of Clinical Oncology (2024)

7063 Background: Non-Hodgkin lymphoma (NHL) is one of the common hematological cancers in the United States (U.S.), accounting for 4% of new cancer cases in 2023. The mortality rate of NHL is the sixth highest among all cancers in the U.S. Our study aimed to examine the trends in NHL mortality and assess the mortality disparities among different sexes, ages, races, geographic locations, and urbanization levels. Methods: Our population-based cross-sectional study analyzed death certificate data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) U.S. from 1999 to 2020 to determine the longitudinal trends of NHL mortality among the U.S. population aged ≥ 15 years. NHL (ICD-10 C82-85) was listed as the underlying cause of death. Age-adjusted mortality rates (AAMRs) per 100,000 individuals were calculated and joinpoint trend analysis were performed to determine the average annual percent change (AAPC) in AAMR trends. Results: From 1999 to 2020, NHL accounted for 457,143 deaths in the United States, of which 54% are men and 46% are women. Excluding unspecified NHL, there were 132,288 (n=132,288/155,957, 84.8%) B cell NHL deaths and 23,669 (n=23,669/155,957, 15.2%) T cell NHL deaths. Overall, the AAMR of NHL decreased from 10.59 (95% CI, 10.46-10.73) in 1999 to 6.21 (95% CI,6.13-6.30) in 2020 with the AAPC of -2.55 (95% CI, -2.63, -2.46). Men had a higher AAMR than women (10.10 [95% CI, 10.06-10.14] vs. 6.29 [95% CI, 6.27-6.32]). Non-Hispanic Whites recorded the highest AAMR (8.43 [95% CI, 8.40-8.45]), followed by non-Hispanic Blacks (5.71 [95% CI, 5.64-5.77]), Hispanics (6.32 [95% CI, 6.25 - 6.40]), American Indians (5.31 [95% CI, 5.04 - 5.58]), and Asians (5.10 [95% CI, 5.00 - 5.19]). Death from NHL was the most common in patients aged 75 years and above (52.50%), followed by patients aged 55-74 years (37.49%) and patients aged 15-54 years (10.41%). Those who lived in the Midwest region had the highest AAMR (8.60 [95% CI, 8.55-8.65], followed by the Northeast region (7.99 [95% CI, 7.94 - 8.05]), the South region (7.73 [95% CI, 7.70 - 7.77]), and the West region (7.58 [95% CI, 7.54 - 7.63]) . The rural population has a higher AAMR compared to the urban population (8.35 [95% CI, 8.29-8.41] vs. 7.86 [95% CI, 7.83 - 7.88]). Conclusions: NHL mortality has declined over the last two decades. The higher mortality rates existed among men, non-Hispanic White individuals, and the rural population warrant targeted intervention to address the mortality disparities.
POS1362 ULTRASOUND OF THE FOREFEET NEXT TO THE HANDS AND WRISTS FOR THE DETECTION OF SUBCLINICAL JOINT-INFLAMMATION IN PATIENTS AT RISK FOR RA: IS IT NECESSARY?
Authors: A. M. P. Boeren, E. Oei, A. Willemze, P. H. P. De Jong, A. H. M. Van der Helm – van Mil, E. Van Mulligen
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Musculoskeletal Ultrasound (US) can be useful to detect subclinical joint-inflammation in patients with clinically suspect arthralgia (CSA) as inflammatory arthritis (IA) is by definition absent. Hands, wrists and forefeet are usually scanned, but it is unclear if the forefeet have additional value in the prediction of arthritis development on top of hands and wrists. <h3>Objectives:</h3> To explore the possibility to omit the forefeet and shorten scanning time, the additional value of US of the forefeet in CSA patients was determined. <h3>Methods:</h3> 298 consecutively included CSA patients of two independent cohorts (CSA Rotterdam and SONAR; cohort 1 and 2) underwent US of the hands (MCP2-5, PIP2-5), wrists and forefeet (MTP2-5) at baseline. All joints were scored according to the EULAR-OMERACT US guidelines. US-positivity was defined as Gray Scale (GS)≥2 and/or Power Doppler (PD) ≥1. Patients were followed for a maximum of 2 years for IA development. We analyzed the association between IA development and US-positivity in i) the full US-protocol (hands, wrists, forefeet), ii) the full US-protocol with correction for GS-findings in the forefeet of healthy individuals (scored positive only if GS ≥3 for MTP2/3) and iii) the protocol without the forefeet (hands and wrists only). Area under the receiver operator curves (AUROCs) were compared. <h3>Results:</h3> In CSA patients with a positive US, subclinical joint-inflammation was most often present in the hands and/or wrists: 86% and 90% in cohort 1 and 2, respectively. Only a small proportion of patients had subclinical joint-inflammation in the forefeet only (14% and 10%, respectively). When using the full US-protocol, US-positivity was associated with IA development in both cohorts (HRs 2.6, 95% CI 0.91-7.5 and 3.1, 95% CI 1.5-6.4; Figure 1). Additional correction of GS in the forefeet showed similar results. Evaluation of the hands and wrists only (without the forefeet) did not change results in both cohorts (HR 3.1, 95%CI 1.4-6.9 and 2.8, 95%CI 1.4-5.6; Figure 1). The AUROCs were comparable between the full protocol and the protocol without the forefeet (0.60 versus 0.67 in cohort 1 and 0.67 versus 0.65 in cohort 2). <h3>Conclusion:</h3> The forefeet can be omitted when US is used for the prediction of IA development in CSA patients. This is due to the finding that subclinical joint-inflammation in the forefeet without concomitant inflammation in the hands/wrist is infrequent. These results allow a shorter US examination. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
Phase 3 randomized double-blind study evaluating selinexor, an XPO1 inhibitor, plus ruxolitinib in JAKi-naïve myelofibrosis.
Authors: John Mascarenhas, Keri Renee Maher, Raajit Rampal, Prithviraj Bose, Nikolai Alexandrovich Podoltsev, Junshik Hong, Xulong Wang, Steve Kye, Claire Harrison
Journal: Journal of Clinical Oncology (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 (&lt;1800 cm 3 vs &gt;1800 cm 3 by MRI/CT scan), and baseline platelet counts (100-200x10 9 /L vs &gt;200x10 9 /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 cm 3 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 10 9 /L. Select exclusion criteria include &gt;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 .
Comparative efficacy of Bruton tyrosine kinase inhibitors in the treatment of relapsed/refractory chronic lymphocytic leukemia: A network meta-analysis (NMA).
Authors: Mazyar Shadman, Jennifer R. Brown, Leyla Mohseninejad, Keri Yang, Heather Burnett, Binod Neupane, Rhys Williams, Nicole Lamanna, Susan M. O'Brien, Alessandra Tedeschi, Constantine S. Tam
Journal: Journal of Clinical Oncology (2024)

7048 Background: Next-generation Bruton’s tyrosine kinase inhibitors (BTKis) have led to changes in the treatment algorithm for patients with high-risk relapsed/refractory (R/R) CLL; defined based on the presence of genetic mutations and a high unmet need. Given the lack of head-to-head trials comparing these treatments in R/R CLL, a NMA was performed to estimate the relative efficacy of BTKis used to treat high-risk patients. Methods: Randomized controlled trials ALPINE (zanubrutinib vs. ibrutinib), ELEVATE-RR (acalabrutinib vs. ibrutinib), and ASCEND (acalabrutinib vs. bendamustine + rituximab/idelalisib + rituximab [BR/IR]) were included in the NMA. High-risk populations were defined based on the pre-specified subgroups within each trial, including patients with del17p and/or TP53 mutations in ALPINE (zanubrutinib: 75/327 and ibrutinib: 75/325), ASCEND (acalabrutinib: 44/155 and BR/IR: 42/155), and del17p/del11q in ELEVATE-RR (acalabrutinib: 268/268 and ibrutinib: 265/265). Bayesian NMAs were used to estimate hazard ratios (HRs) or odds ratios (ORs) with 95% credible intervals (CrIs), and probability better (PB) for zanubrutinib versus all other treatments. Outcomes analysed included investigator-assessed progression-free survival (PFS), overall survival (OS), overall response (ORR), and complete response (CR). Given the timing of the included trials in relation to the COVID-19 pandemic, ALPINE data were analyzed with and without adjustment for COVID-19 related deaths. Results: The NMA found a statistically significant improvement in PFS for zanubrutinib over acalabrutinib in high-risk patients and a trend towards improvement in OS, ORR, and CR (Table). Zanubrutinib led to statistically significant improvements in PFS versus ibrutinib (HR [95% CrI]: 0.49 [0.30, 0.78], PB: 99.9%) and BR/IR (0.12 [0.05, 0.26], PB: 100.0%). For OS, zanubrutinib showed a trend towards improvement versus ibrutinib (0.59 [0.31, 1.12] PB: 94.8%) and BR/IR (0.64 [0.24, 1.74] PB: 80.7%). Conclusions: This NMA found zanubrutinib to be the most efficacious BTKi for patients with high-risk R/R CLL, offering significantly delayed disease progression, and favourable survival and response vs. alternative BTKi treatments. [Table: see text]