tbuckley/cabot-search huggingface dataset:
Cardiovascular and hematologic complications of Hodgkin vs non-Hodgkin lymphoma and readmission trends: A National Readmission Database analysis from years 2016-2020.
Authors: Sindhu Chandra Pokhriyal, Waleed Alruwaili, Ruchi Yadav, Amulya Bellamkonda, Binit Aryal, Tutul Chowdhury, Kalpana Panigrahi, Madhumati R. Kalavar, Boris Avezbakiyev
Journal: Journal of Clinical Oncology (2024)

e19034 Background: Cardiovascular complications are a leading cause of non-malignant death in lymphoma survivors. We sought to analyze the national readmission trends and evaluate the in-hospital mortality as well as the cardiovascular and hematological complications in lymphoma patients using the National Readmission Database (NRD). Methods: We selected patients aged &gt;=18 years of age, from the NRD between the years 2016-2020 to generate a cohort of Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL) patients using ICD-10 codes. The primary outcome was in-hospital mortality, and the secondary outcome was cardiovascular and hematologic complications of HL vs NHL after adjusting for demographic confounders. We used multivariate logistic regression and propensity score matching (PSM) using STATA v.18. We also analyzed the 30-day readmission trends in these patients. Results: A total of 1,016,338 NHL and 83,036 HL patients were included in the analysis. After matching for demographics confounders, on PSM analysis we found that in-hospital mortality was higher in NHL vs HL (5.9% vs 4.42%; p-value 0.001). The cardiovascular complications that were studied included cardiac tamponade (0.69% in NHL vs 0.4% in HL; p-value 0.001), pericarditis (0.13% in NHL vs 0.14% in HL; p-value 0.717) and anthracycline cardiomyopathy (0.47% in HL vs 0.85% in NHL; p-value 0.001). The hematological outcomes studied included myelodysplastic syndrome (0.71% in NHL vs 0.64% in HL; p-value 0.210), acute leukemia (0.48% in NHL vs 0.44% in HL; p-value 0.43), and myelosuppression (18.59% vs 13.73%; p-value 0.001). A 30-day readmission trend analysis showed a longer length of stay in NHL vs HL (5.34 days vs 4.77 days) while the total inflation-adjusted cost was higher in HL vs NHL (20,989 dollars vs 17176 dollars). Conclusions: An NRD analysis of NHL and HL patient populations from 2016-2020 reflected a slightly increased mortality rate, higher incidence of cardiovascular complications and a longer length of stay in NHL patients. [Table: see text]
Real-world understanding of the unmet need for treatment of non-covalent BTKi in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).
Authors: Rushir J. Choksi, Jing-Zhou Hou, John Li, Mike Gart, Anupama Vasudevan, Simon Blanc
Journal: Journal of Clinical Oncology (2024)

e19028 Background: Non-covalent (nc) Bruton Tyrosine Kinase inhibitors (BTKi) for the treatment of Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (CLL/SLL) provide patients with a new treatment option after resistance to on-target BTK mutations or PLCγ2 mutations that bypass BTK inhibition. Given the December 1, 2023 accelerated FDA approval for pirtobrutinib, a nc-BTKi, in the treatment of CLL/SLL for treatment of patients who have received at least two prior lines of therapy with a covalent (c) BTKi and a B-Cell Lymphoma 2 Protein Inhibitor (BCL2i), we sought to understand the addressable population for treatment with nc-BTKI therapy in a real-world database of CLL/SLL patients. Methods: We used the Integra Connect PrecisionQ real-world de-identified database of over 3 million cancer pts across 500 sites of care to identify CLL/SLL pts for the analysis. The CLL patients included for the analysis were on a treatment in 2023 and must have had either &gt;5 CLL/SLL diagnosed visits or more CLL/SLL visits than non-CLL/SLL visits if &lt;5 CLL/SLL diagnosed visits. Descriptive analyses were used for this study. Results: Of the 6,992 patients treated for CLL/SLL in 2023, the median age at treatment start was 71, 62% were male, 65% identified as White, 6% as African American, and 29% as Other. Of the pts, 12% received a c-BTKi and BCL2i, 64% received a c-BTKi only, and 12% received a BCL2i only. Of the 12% of pts who received a c-BTKi and BCL2i, 191 pts started a subsequent line of therapy. Among pts who received a c-BTKi and BCL2i, 79% received a BTKi therapy first, 10% received a BCL2i therapy first, and 12% had a line of therapy with both a BTKi and BCL2i. We found 59 pts who received nc-BTKi; among those pts, 51% received a c-BTKi and BCL2i prior to initiation of nc-BTKi. The median age at first treatment for CLL/SLL was 71.7 for those who received a c-BTKi, 71.1 for those who received a BCL2i, and 70.8 for those who received nc-BTKi. The median age at first diagnosis for CLL/SLL was 68 for those who received a c-BTKi, 66 for those who received a BCL2i, and 63 for those who received nc-BTKi. The median time to first treatment was 470 days for pts treated with a c-BTKi, 507 days for pts treated with BCL2i, and 587 days for pts treated with nc-BTKi. Conclusions: We found that among nearly 7,000 treated patients in the database, 12% were treated with both a c-BTKi and BCL2i; of those, just 23% started a subsequent treatment. Among patients who were treated with a nc-BTKi we found their median age at treatment start and diagnosis was lower than those who received a c-BTKi or BCL2i respectively.
Long-term follow-up of patients with hairy cell leukemia treated with different modalities at a single institution: Real-life experience over 25 years.
Authors: Muneer Khan, Marcelle Meseeha, Julie L. Richards, Joyson Poulose, Giampaolo Talamo
Journal: Journal of Clinical Oncology (2024)

e19023 Background: Hairy cell leukemia (HCL) is an uncommon and indolent leukemia of mature B cells, accounting for 2% of all lymphoid neoplasms. We analyzed characteristics, treatment modalities, response rates, and survival of HCL patients followed at our institution. Methods: We retrospectively reviewed data from the medical records of 56 consecutive HCL patients evaluated in our Hematology/Oncology clinic between 1998 and 2023. Results: The median age at diagnosis was 59 years (range, 37-94). Forty-nine patients (87%) were male. First-line therapy was cladribine in 30 patients (54%), cladribine + rituximab in 6 patients (11%), observation in 5 patients (9%), and another modality (fludarabine, pentostatin, single agent-rituximab, and other) in the rest of patients. The median follow-up was 122 months (1-291). The overall response rate was 96%. CR and PR rates were 68% and 28%, respectively. Relapses were observed in 44% of patients. The median OS was not reached, and the median PFS was 181 months (95% CI, 128-252). The 5-year and 10-year PFS were 78% and 29%, respectively. Only 3 patients (5%) died as a result of HCL, either indirectly from immune suppression (pneumonia, 2 patients) or directly (cachexia in 1 patient, untreated because of advanced age and comorbidities). Conclusions: Treatment with purine analogues such as cladribine, plus or minus rituximab, achieves deep and durable responses in most HCL patients. Although relapses were commonly observed, the vast majority of HCL patients did not die as a result of HLC.
Real-world comparison of time to next treatment for patients with high-risk CLL/SLL in first line of treatment.
Authors: Jing-Zhou Hou, John Li, Anupama Vasudevan, Mike Gart, Rushir J. Choksi, Simon Blanc
Journal: Journal of Clinical Oncology (2024)

e19027 Background: The International Workshop on CLL recommends testing patients (pts) with CLL/SLL for deletion 17p (del17p) and tumor protein (TP) 53 mutations for prognosis and treatment decisions. Both Bruton Tyrosine Kinase inhibitors (BTKi) and B-cell lymphoma 2 protein inhibitor (BCL2i) are approved as effective frontline therapies for CLL/SLL pts, particularly those with high-risk features such as del17p and TP53. However, there is no clinical study directly comparing the efficacy of BTKi and BCL2i. We sought to understand the real-world use of BTKi and BCL2i as well as the differences in time to next treatment, a surrogate for progression-free survival, among CLL/SLL pts who were identified as having either del17p or TP53 mutations and treated with a BTKi or BCL2i in the 1L setting. Methods: We used the Integra Connect PrecisionQ real-world de-identified database of over 3 million cancer pts across 500 sites of care to identify CLL/SLL pts for the analysis. We observed pts who started 1L treatment between 3/4/2016 and 12/4/2023. Risk status was captured via medical chart curation to determine the presence del17p or TP53 mutations. Time to next treatment was measured from the treatment start to the first of the initiation of a subsequent line of therapy or death. Descriptive analyses were used and time to next treatment was analyzed using a Kaplan Meier analysis. Results: We identified 295 CLL/SLL pts with high-risk features. The median (IQR) age of these pts at treatment start was 74 (66,81) years old, 62% were male, 77% identified as White, 8% as African American, and 15% as Other. Of these high-risk pts, 72% had only a deletion 17p, 13% had only TP53 mutation, and 15% had both. The percent of high-risk pts who received a BTKi in 1L was 69% with a median (IQR) age of 75 (65, 81) at treatment start, while 13% received a BCL2i in 1L with a median (IQR) age of 70 (64,77) at treatment start. The percent of pts who received neither a BTKi or BCL2i in 1L was 18% with median (IQR) age of 74 (68,80) at treatment start. The median time to next treatment for those who received a BTKi was 68.4 months (95% Confidence Interval [CI]: 48.4, NA) compared to 45.5 months (CI: NA, NA) for pts who received a BCL2i. The median (IQR) duration for patients treated with a BCL2i +/- obinutuzumab was 396 (285,603) days. The probability of pts who did not initiate a next treatment at 30 months was found to be 71% (95% CI, 64% to 78%) for those who received a BTKi (p &lt;0.05) compared to 92% (95% CI, 83% to 100%) for those who received a BCL2i. Conclusions: The real-world data comparison of 1L treatment in high-risk pts with CLL/SLL shows that, after 30 months, the probability of not initiating the next treatment is 92% for those treated with a BCL2i compared to 76% for those treated with a BTKi. Additional follow-up and a larger sample may be needed to further validate these findings.
Therapeutic utilization in chronic lymphocytic leukemia: A cross-sectional analysis of the Lymphoma Coalition’s 2022 Global Patient Survey.
Authors: Steve Kalloger, Amanda Watson, Shawn Sajkowski, Lorna Warwick
Journal: Journal of Clinical Oncology (2024)

e19026 Background: Chronic Lymphocytic Leukemia (CLL) is a highly prevalent disease with heterogenous prognostic trajectories. With a multitude of treatment options, we sought to explore therapeutic utilization trends from a global perspective in order to gain a more in-depth understanding of how different treatment regimens are utilized in different health systems. Methods: In 2022, The Lymphoma Coalition designed and globally deployed a survey to patients with lymphoma and CLL in order to gather patient reported outcomes and patient reported experience measures. Data were collected and enumerated with relevant contingency analyses performed to determine associations with a particular treatment regimen in the context of CLL. Results: The entire cohort of patients with CLL was 1289. The median age of the cohort was 65 and ranged from 26 to 97 years old. Biological sex was equally distributed with 50.5% of respondent indicating that they were female. Respondents were derived from 29 countries. The top three contributors to each region were China (50%), Australia (25%) and New Zealand (18%) for Asia-Pacific (N = 227); France (50%), Italy (13%) and Sweden (7%) for Europe (N = 950); Canada (75%) and The United States (25%) for North America (N = 112). Of those, 636 indicated that they received at least one therapy. The use of chemo-immunotherapy was most common (42%) followed by targeted therapy (32%), immunotherapy alone (18%), and chemotherapy alone (16%). Neither age nor biological sex was a significant predictor of therapy. Europe had the highest rates of chemo-immunotherapy utilization (45%) with North America and Asia-Pacific indicating 32% respectively (p = 0.01). Targeted therapy was used at a higher rate in North America (45%) but failed to demonstrate a significant difference against Asia-Pacific and Europe (31%); (p=0.10). Both immunotherapy and chemotherapy alone failed to demonstrate significant differences across regions. Conclusions: The data support that the majority of patients with CLL who require treatment are most likely to receive combination chemo-immunotherapy utilizing rituximab. However, we acknowledge that the data presented here is two years old and that the use of targeted molecular therapy is likely increasing. We found it reassuring that we could not identify any biases in the administration of the therapeutic regimens across the demographics of age and biological sex. Our research in this space will continue as we have deployed the 2024 version of the Global Patient Survey and have focused on increasing respondent participation from North America. With this new data, we plan on producing a time-dependent model to investigate how emerging therapies enter and expand in the CLL therapeutic space.
Concordance of PD-L1 combined positive score (CPS) analysis between primary gastric cancer and matched peritoneal metastasis.
Authors: Valentina Massa, Francesca Salani, Giada Grelli, Virginia Genovesi, Caterina Vivaldi, Francesca Signorini, Clara Ugolini, Maria Elena Filice, Laura Bernardini, Silvia Cesario, Miriam Caccese, Jessica Graziani, Linda Bartalini, Dario Berra, Francesco Mangogna, Vincenzo Nardini, Gianluca Masi, Lorenzo Fornaro
Journal: Journal of Clinical Oncology (2024)

e16068 Background: Peritoneum represents one of the most common metastatic sites of gastroesophageal adenocarcinoma (GEA) and is associated with poor prognosis. Programmed death-ligand 1 (PD-L1) expression is a recognized predictive biomarker of response to immune checkpoint inhibitors (ICIs) in the first-line setting. However, data from pivotal trials showed poorer clinical efficacy of ICIs in the sub-set of patients with peritoneal involvement, regardless of PD-L1 score magnitude. Here, we investigated the temporal and spatial heterogeneity of PD-L1 expression between primary tumor and matched peritoneal metastasis. Methods: PD-L1 expression according to CPS was determined by immunohistochemistry using VENTANA PD-L1 (SP263) assays on formalin-fixed paraffin-embedded (FFPE) tumor tissues derived from 22 patients treated at our institution for advanced GEA from September 2015 to August 2023. Concordance rate of PD-L1 expression between primary tumor and matched peritoneal metastasis using PD-L1 CPS cut-off of 1 and 5 was reported (spatial heterogeneity); additionally, concordance between PD-L1 value before and after the administration of systemic treatments was analyzed (temporal heterogeneity). Results: 12(54.5%)/5(22.7%) primary tumor samples and 12(54.5%)/1(4.5%) peritoneal metastases showed PD-L1 CPS ≥ 1/ ≥ 5, respectively. Concordance of PD-L1 CPS between primary and peritoneal specimens was 54.5% and 72.7% according to CPS cuts-off of 1 and 5, respectively, highlighting marked spatial heterogeneity. High concordance rate (94%) was reported between negative PD-L1 CPS primary tumor samples and matched peritoneal metastases, against the cut-off of CPS ≥ 5; in contrast, none of the positive primary tumor samples retained PD-L1 expression in the peritoneum. Evident temporal heterogeneity of PD-L1 expression was also observed, with 56% concordance against CPS ≥ 5 in the pre- versus post-treatment comparison. Conclusions: PD-L1 expression in GEA is characterized by spatial and temporal heterogeneity which is more prominent for lower CPS cut-offs values. This evidence could hamper its role as predictive biomarker for ICIs. The high intra-patient discordance rate of PD-L1 CPS expression between positive primary tumor samples and matched peritoneal metastases suggests that peritoneal specimens should not be recommended as the preferred source for PD-L1 assessment.
Phase I safety and preliminary efficacy of IMM0306 in combination with lenalidomide in patients with relapsed or refractory CD20-positive B-cell non-Hodgkin's lymphoma.
Authors: Yanyan Liu, Ningjing Lin, Zhihua Yao, Jiuyang Zhang, Wei Meng, Zhenjiu Wang, Qiying Lu, Wenzhi Tian, Yuqin Song, Jun Zhu
Journal: Journal of Clinical Oncology (2024)

e19040 Background: The combination of rituximab (anti-CD20 mAb) and lenalidomide was approved for use in relapsed or refractory (R/R) indolent non-Hodgkin's lymphoma (iNHL). IMM0306 is a fusion protein of CD20 monoclonal antibody with the CD47 binding domain of SIRPα on both heavy chains. It exerts excellent cancer killing efficacy by activating both macrophages and NK cells via blockade of CD47-SIRPα interaction and FcɣR engagement. Here, we report on a Phase I study of 8 patients (pts) with R/R CD20-positive B-cell NHL. Methods: This is an open-label, multicenter phase I study (NCT05771883). The study is designed to use "3+3" scheme for dose escalation exploring in 2 dose levels of IMM0306 (1.6 mg/kg, 2.0 mg/kg), intravenously administered each week in each 28-day cycle; while lenalidomide will be administered as fixed dose of 20 mg for NHL, taken orally once daily for the first 21 days of each 28-day cycle to determinate maximum tolerated dose (MTD). Dose-limiting toxicity (DLT) was evaluated in the first 28 days of the combination therapy. Safety was evaluated per CTCAE 5.0, tumor assessments performed once every 8 weeks by Lugano 2014. Results: As of Jan 5, 2024, 8 pts with R/R follicular lymphoma (FL, n=6) and marginal zone lymphoma (MZL, n=2) were enrolled. The median age was 52.5 years with 7 (87.5%) males. The median prior line of therapy was 1. All pts received previous anti-CD20 therapy. Among 7 efficacy evaluable pts, 1 CR (FL), 4 PR (2 FL, 2 MZL), and 1 SD were seen. The ORR and DCR were 71.4% and 85.7%, respectively. Two DLTs (grade 4 PLT decreased without bleeding) were observed at 2.0 mg/kg IMM0306 + 20 mg Lenalidomide dose level, but none at the dose level of 1.6 mg/kg IMM0306 + 20 mg Lenalidomide. The most common treatment related adverse events (TRAEs) were lymphocyte decreased (62.5%), ANC decreased (62.5%), WBC decreased (50%), anemia (50%), bilirubin increased (50%), PLT decreased (37.5%), infusion-related reactions (37.5%). Grade ≥3 TRAEs occurred in 6 pts, including lymphocyte decreased (62.5%), PLT decreased (25%), WBC decreased (12.5%), ANC decreased (12.5%) and pneumonia (12.5%). One pt experienced treatment related serious adverse event. 5 patients experienced TRAEs, leading to the study drug interruption, while no patients experienced TRAEs leading to the study drug discontinuation or death. 2 pts had a dose reduction of IMM0306 (2.0 mg/kg dose level), 3 pts had dose reductions of lenalidomide due to TRAEs. Pharmacodynamics analysis demonstrated IMM0306 combine lenalidomide effectively depleted B cell in peripheral blood within 24 hours. Conclusions: 1.6 mg/kg IMM0306 in combination with 20 mg lenalidomide was well-tolerated and with a robust preliminary anti-tumor activity in pts with R/R FL and MZL. The phase I study is ongoing. Clinical trial information: NCT05771883 .
Orelabrutinib, rituximab, temozolomide and high-dose methotrexate (RMOT) in newly diagnosed primary central nervous system lymphoma (PCNSL): A retrospective analysis on efficacy and safety.
Authors: Yi Xia, Qingqing Cai, Peng Zhang, Xiaopeng Tian, Xiaojie Fang
Journal: Journal of Clinical Oncology (2024)

e19041 Background: PCNSL is a rare, aggressive malignant tumor and has a poor prognosis. HD-MTX-based regimen is the first-line treatment of PCNSL. Orelabrutinib is a novel, potent, highly selective BTK inhibitor with a high CSF concentration. Recent evidence has shown the efficacy and safety of orelabrutinib in PCNSL. Therefore, we conducted a retrospective study of clinical outcomes in newly diagnosed PCNSL patients (pts) treated with RMOT regimen in routine clinical care. Methods: This retrospective cohort included the pts (aged 18-80 years) with newly diagnosed PCNSL who received 6 cycles of RMOT regimen (rituximab 375 mg/m2 iv day 1; MTX 3.5 g/m2 iv day 1; temozolomide 150 mg/m2 po day 1 to day 5; orelabrutinib 150 mg qd po; 4 weeks per cycle) as the first-line induction therapy between Nov. 2021 and Aug. 2023. All the pts were proposed to receive orelabrutinib monotherapy as maintenance after RMOT therapy. We recommend to receive autologous stem cell transplantation (ASCT) or whole brain radiation therapy (WBRT) as consolidation after RMOT therapy. Efficacy was assessed by MRI/PET per the International PCNSL Collaborative Group (IPCG) criteria. The primary endpoint was overall response rate (ORR); secondary endpoints were CR rate, progression-free survival (PFS), overall survival (OS), and safety. Results: Ten pts (6 males) with PCNSL were included, with a median age of 61 years (range, 45-77). All pts had a histologically confirmed diffuse large B-cell lymphoma. 4 pts (40%) underwent WBRT after induction therapy. As of the cut-off date (December 31, 2023), the median follow-up time was 9.7 (range, 4.8-25.7) month. All pts were evaluated for the treatment response. An interim evaluation after 4 cycles was available for 10 pts, showing complete remission (CR) rate of 80% (8/10), partial response (PR) rate of 20% (2/10), giving an ORR of 100.0% (10/10, Table). At data cutoff, the best ORR was 100.0% (10/10), with all pts achieved CR. Of 10 responders, 9 had an ongoing response, and 1 died of covid-19 infection. Median PFS/OS was not reached (NR) (95% CI NR-NR). The most common AEs were anemia, other include white blood cell or platelet count decreased. Reported AEs were generally manageable and resolved soon after supportive treatment. Only 1 (10%) pts experienced ≥grade 3 AEs—acute kidney injury. No treatment-related death occurred. Conclusions: This retrospective data suggested that RMOT had an encouraging anti-tumor activity in newly diagnosed PCNSL pts, with a toleratable safety profile. This orelabrutinib-containing regimens may provide a potential treatment strategy for pts with PCNSL. [Table: see text]