bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early data from a phase II trial investigating the combination of pembrolizumab (PEM) and entinostat (ENT) in relapsed and refractory (R/R) Hodgkin lymphoma (HL).
Authors: Sermer David J. , Vardhana Santosha Adipudi , Ames Ashley , Biggar Erin , Moskowitz Alison J. , Batlevi Connie Lee , Caron Philip , Hamilton Audrey M. , Moskowitz Craig H. , Matasar Matthew J. , Zelenetz Andrew David , Horwitz Steven M. , Von Keudell Gottfried , Yahalom Joachim , Rademaker Jurgen , Dogan Ahmet , Seshan Venkatraman E. , Younes Anas 
Published: May 2020

e20018 Background: Histone deacetylase (HDAC) inhibitors have single agent activity in various types of lymphoma. They have been shown to restore antigen-specific immune recognition in cancer cells and to downregulate PD-1 expression in circulating T lymphocytes. In preclinical studies, the combination of HDAC inhibitors and anti-PD-1 antibodies acts synergistically against various tumor models in mice. Accordingly, we investigated the safety and efficacy of the novel combination of the HDAC inhibitor ENT and the PD-1-blocking antibody PEM in patients with R/R HL. Methods: Patients with R/R HL received ENT 5-7 mg orally once weekly and PEM 200 mg intravenously once every three weeks. The primary objective is overall response rate (ORR) and 12-month progression-free survival (PFS). Multiplexed serum cytokine analysis of 20 pro-inflammatory cytokines and chemokines was performed on sera from peripheral blood samples collected at baseline and at 21 days on treatment. Results: At data cutoff on 2/5/20, 14 patients with HL have been enrolled. Out of 13 evaluable patients, 12 responded (92% ORR), including 3 who progressed on prior anti-PD-1 therapy. With a median duration of follow-up of 176 days (21-632), 9 patients are currently receiving treatment on study, 2 discontinued due to toxicity, 1 for progression, and 2 for consolidation with transplant or radiation. After 21 days on treatment, there was a decrease in median serum levels of eotaxin (-39%, p = 0.002), eotaxin-3 (-56%, p = 0.04), MDC (-78%, p = 0.025), MIP1a (-60%, p = 0.025), and TARC (-98%, p < 0.001) and a 3-fold increase in median levels of IFNγ (p = 0.032). There was an association between extent of tumor reduction and greater decrease in the cytokines eotaxin-3 (-62%, p = 0.064), MDC (-90%, p = 0.064), and MIP1a (-85%, p = 0.064), which trended towards statistical significance. Out of 22 total patients enrolled in this study (including 8 patients with follicular lymphoma), 62% had grade ≥3 adverse events (AE), which were predominantly hematologic, including neutropenia (48%), thrombocytopenia (19%), and anemia (10%). Immune-related AEs included 3 cases of hypothyroidism, 2 cases of hepatitis and 1 case of pneumonitis. Four patients who experienced serious AEs due to pericarditis (n = 2), hemophagocytic lymphohistiocytosis, and bullous dermatitis were taken off study. Conclusions: Early results from this ongoing phase II clinical trial suggest that the combination of PEM and ENT is safe with encouraging responses in HL. Clinical trial information: NCT03179930 .
Clinical anti-lymphoma effect of T cells expressing an anti-CD19 chimeric antigen receptor in synthetic biology optimizing system.
Authors: Dai Hong-jiu , Li Yanyun , Shi Lan , Dai Hui , Li Yan , Xu Hui , Zhu Jingjing , Zhang Pei-xian 
Published: May 2020

e20021 Background: Anti-CD19 chimeric antigen receptor (CAR) T cells for relapse/refractory B-cell malignancies has been remarkably effective in previous clinical trials. However, most of subjects has severe adverse effect even though the infusion of CAR T cells is at the low dose. Herein, we investigated the safety of administering CAR T cells which express the anti-CD19 chimeric antigen receptor in synthetic biology optimizing system. Methods: We designed an anti-CD19 CAR with FMC63 Scfv (KD-019). This CAR has a CD8 hinge and transmembrane domains and a 4-1BB costimulatory domain; T cells expresses CAR in synthetic biology optimizing system. A phase I dose-escalation trial was conducted to investigate the safety of KD-019 CAR T cells and to assess efficacy for patients with previously treated B-cell lymphoma. The patient at the 76 years old received Flu/Cy chemotherapy to enhance CAR T cells activity. Two days after the completion of chemotherapy, about 3 million KD-019 CAR T cells were infused. Results: The patient who has chemotherapy-refractory lymphoma has received KD-019 CAR T cells infusion. Post infusion KD-019 CAR T cells expansion were observed; peak CAR T cells level occurred between Day 3 and 10, and CAR T cells were still detected on Day 243. In addition, we found that CD3+CD8+ T cells level peaked on Day 15. Moreover, after infusion of CAR-T cells, the right peripheral pulmonary lymphaden and visible nodules were respectively shrunk by 53% and 85% on Day 28; and some peripheral pulmonary nodules were obviously reduced and nearly disappeared. We also found that pelvic effusion was significantly reduced, and pain symptoms of the left hip and leg were reduced by 50%. Exhilaratingly, our KD-019 CAR therapy has no obvious cytokine release syndrome (CRS) and central nervous system toxicity. Conclusions: KD-019 CAR T cells express an anti-CD19 chimeric antigen receptor in synthetic biology optimizing system. this innovative KD-019 product can offer significant clinical benefit for NHL patients at the low dose without fever and neurotoxicity. Clinical trial information: NCT03854994. Clinical trial information: NCT03854994 .
Post-transplant lymphoproliferative disorder (PTLD) after solid organ transplant (SOT): A multicenter real world analysis (RWA) of 877 patients (pts) treated in the modern era.
Authors: Jagadeesh Deepa , Tsai Donald Edward , Wei Wei , Alvarez Bustamante Jean , Wagner-Johnston Nina D. , Berg Stephanie , Kim Seo-Hyun , Reddy Nishitha M. , Sriram Deepika , Portell Craig , Ghione Paola , Voorhees Timothy , Kamdar Manali K. , Koff Jean Louise , Dharnidharka Vikas , Evens Andrew M. 
Published: May 2020

e20026 Background: Historically, SOT PTLD have modest outcomes in part due to heterogeneous treatment approaches. Additionally, there remains an absence of a large data repository in PTLD to help delineate contemporary pt outcomes & prognostic factors. We conducted a large, multicenter RWA to study outcomes & prognostication of SOT PTLD in the modern era. Methods: Retrospective data on 877 untreated SOT PTLD pts ages ≥18 years (yrs) (2000-2018) were analyzed from 15 academic centers. Prognostic factors for relapse free survival (RFS) & overall survival (OS) were assessed by Cox model. Results: The median age at diagnosis was 54 yrs (range 18-84). The majority of pts were white (78%) & male (67%). Median time from SOT to PTLD diagnosis was 57 months (range 0.23-470). SOT types: kidney (41%) liver (19%), lung (16%), and heart (11%); 11% multi-organ. Tumor was EBV+ in 52%. Graft involvement (18%) and rejection (21%) were seen in a proportion of pts. Most pts had reduction in immunosuppression (79%) and rituximab (R)-containing regimen (61%) as part of 1st line therapy (Tx). Most common Tx: R monotherapy (34%), R+chemotherapy (29%) & chemotherapy without R (8%). Maintenance R use was infrequent (6%). Overall response rate was 63% [51% complete response (CR) and 12% partial response (PR)] and 19% of pts had primary refractory disease. With 44-month median follow-up (0.1-304), 62% of pts were alive. Median OS & RFS for all pts were 12 & 9 yrs, respectively, while differential survival rates were identified for several pt subsets (Table). On univariate analysis, lung SOT was associated with borderline RFS (HR 0.68 [95% CI 0.44-1.03], P= 0.07) and inferior OS (HR 0.67 [95% CI 0.49-0.91], P= 0.012), while EBV negative PTLD was associated with poorer RFS (HR 1.51 [95% CI 1.12-2.04, P= 0.006). In addition, achievement of PR to 1st line Tx vs CR was strongly prognostic for inferior RFS (HR 2.58 [95% CI 1.88-3.54], P< .0001) and OS (HR 2.30 [95% CI 1.60-3.29], P< .0001). Conclusions: In this large, multicenter PTLD RWA, type of SOT was strongly associated with long-term RFS and OS and EBV status predicted RFS. Furthermore, depth of response to 1st line Tx was a critical determinant for long-term pt survival. [Table: see text]
Hepatosplenic T-cell lymphoma: The Mayo Clinic experience.
Authors: Bojanini Molina Leyla , Alhaj Moustafa Muhamad , Parrondo Ricardo Daniel , Seegobin Karan , Hastings Jacquelyn , Gannon Nicole , Hoppe Bradford , Menke David M , Kharfan-Dabaja Mohamed , Ayala Ernesto , Jiang Liuyan , Tun Han W. 
Published: May 2020

e20036 Background: Hepatosplenic T cell lymphoma (HSTL) is a rare subtype of mature T cell lymphomas accounting for less than 1 percent of non-Hodgkin lymphomas. it has been associated with poor prognosis. It typically involves sinusoids in the spleen, liver, and bone marrow. Methods: Following IRB approval, we retrospectively evaluated patients with HSTL treated at the Mayo Clinic Cancer Center 1996-2019. Kaplan-Meier survival analysis and univariate analysis to identify prognostic factors were performed. We investigated clinical characteristics and outcomes among patients with HSTL. Results: 22 patients (15 males) with median age of 45.5 years (range- 15.5-80.6) were identified. The majority of patients had B symptoms (12/22), cyotpenias (20/22), massive splenomegaly (16/22), liver involvement (13/22), and/or bone marrow involvement (14/22). Additionally, 42% tested positive for peripheral blood involvement and 8/22 (36%) were on chronic immunosuppression related to solid organ transplant (2), inflammatory bowel disease (2), and rheumatologic disorders (4). Phenotypically, the majority of patients were positive for gamma/delta (18/22), isochromosome 7q (8/13), and 4/9 (44%) tested positive for trisomy 8. Initial therapies included CHOP/CHOEP (14), ICE (2), EPOCH (1), pentostatin (1), and radiation (1). The median follow-up was 33 months (range 2,137). Progression free survival and overall survival (OS) were 9.5 months (95% CI; 1.8, 16.3) and 12 months (95% CI; 4.9, 18.5) respectively. 10/22 (45%) underwent splenectomy with one patient receiving splenectomy alone as treatment. 8/22 (36%) had stem cell transplant (SCT- 5 allogeneic and 3 autologous). Out of the 22 patients 4 (18%) were long-term survivors with 55, 74, 95, and 137 months; 3/4 had splenectomy at diagnosis and 2/4 had allogeneic SCT. The longest survivor had splenectomy only. Liver involvement was associated with worse OS; 10 months (95% CI; 1.6, 18) vs 35 months (95% CI; 4, NR), p = 0.036. Immune suppression at diagnosis was associated with worse OS; 5 months (95% CI; 1.3, 18) vs 18 months (95% CI; 9, 74), p = 0.036. A trend for better OS was seen with splenectomy and SCT. Conclusions: HSTL is a rare lymphoma with poor prognosis. Long-term survival was seen in 18% only. Liver involvement and immune suppression had a negative impact on OS. A larger cohort is needed to better evaluate the impact of different treatment options.
Phase Ib study of brentuximab vedotin (BV) with low-dose total skin electron beam (LD-TSEB) for treatment of mycosis fungoides (MF) and Sezary syndrome (SS).
Authors: Song Shiyu , Holkova Beata , Mukhopadhyay Nitai , Williamson Daeryl , Dickinson Molly 
Published: May 2020

e20037 Background: MF is generally not curable, causing severe symptoms and eventually leading to patient (pt) death. LD-TSEB is currently used for diffuse skin lesions but with short duration of response. BV is effective and approved for MF but also limited by short duration of response. In this study we proposed to evaluate the feasibility of combining these 2 treatments by assessing the safety and response rate/duration in these pts. Methods: Pts with stage IB - IVA CD30+ MF or SS who were candidates for TSEB were recruited for a 2-cohort open-label phase 1b trial. Cohort A included pts with earlier stage disease; cohort B included pts with more advanced disease. BV was given at 1.8 mg/kg 3 wks before initiation of TSEB and then every 3 wks. Pts in Cohort A received 3 doses of BV; pts in Cohort B continued BV until disease progression or unacceptable toxicity, up to 2 years. Standard 12 Gy TSEB was administered in 6 fractions (2/wk) beginning 3 wks after the first dose of BV. The Modified Severity Weighted Assessment Tool (mSWAT) was used to determine skin involvement at baseline and during and after treatment. Skindex-16 was used to assess pt-reported symptoms and toxicities. Pts were seen weekly during TSEB, monthly after TSEB, and every 3 months after the last dose of BV for response evaluation and time to progression (TTP). Results: Five pts were enrolled and treated in this study. Two were enrolled to Cohort A, and 3 were enrolled to Cohort B. One pt in Cohort B expired before completing study treatment due to comorbidity unrelated to MF. The other pt data is listed in the table. None of the pts developed grade 4 or 5 toxicities; pt 1 developed recurrent neuropathy and stopped BV after 5 cycles. Conclusions: As BV became approved for the indication, accrual slowed, and the trial was stopped with very few pts. These pt cohorts are heavily treated before trial entry, making conclusions regarding response hard to generalize. However, the combination of BV and TSEB is well tolerated with no significant increase in skin toxicity. Response rate seems comparable to current standard of care, though with no improvement in duration of response over BV alone. Clinical trial information: NCT02822586 . [Table: see text]
Prognostic value of event-free survival at 24 months for adolescent and adult T-cell lymphoblastic lymphoma.
Authors: Chen Haizhu , Shi Yuankai 
Published: May 2020

e20042 Background: T-cell lymphoblastic lymphoma(L-LBL) has an aggressive clinical behavior. To date, powerful and consistent prognostic factors have not been established for adolescent and adult T-cell lymphoblastic lymphoma. In this study, we firstly evaluated the prognostic value of event-free survival (EFS) at 24 months (EFS24) for adolescent and adult T-LBL. Methods: Between January 2006 and December 2017, 91 adolescent and adult patients (aged≥12 years) with newly diagnosed T-LBL and treated with chemotherapy were retrospectively analyzed. EFS was defined as the time from initial diagnosis to relapse or progression, retreatment, death from any cause, or to the last follow up. Subsequent OS was defined as time from achieving EFS24 or time from progression in patients who did not achieve EFS24 to death from any cause or last follow-up. Results: In total, 91 patients with previously untreated T-LBL who had a median age of 24 years were enrolled. At a median follow-up of 40.4months (range, 1.4 to 163.3 months), the 5-year OS and EFS was 47.9% and 45.5%, respectively. Of all patients, 45(49.5%) achieved EFS24 and 46(50.5%) did not. EFS24 was associated with a markedly superior outcome, compared with no achievement of EFS24(5-year OS, 90.5% vs 3%). In addition, the median subsequent OS for patients achieving EFS24 was not reached (5-year subsequent OS, 84.9%), whereas median subsequent OS for patients without achieving EFS24 was only 5.5months (5-year subsequent OS, 2.7%). Multivariate analysis demonstrated that only response to treatment (CR vs no CR) was significantly associated with EFS (HR =0.219,95% CI 0.118-0.404, P < 0.001), and EFS24 achievement was an independent prognostic indicator for OS (HR = 0.044, 95% CI 0.016-0.120, P < 0.001). Conclusions: We confirm that EFS24 is an independent prognostic factor for OS, which can aid clinicians in discussions of risk stratification and in selection of subsequent treatments. Further validation in the context of directed prospective clinical trials is warranted.
Incidence of second primary malignancy (SPM) in patients with mucosa-associated lymphoid tissue lymphoma (MALToma).
Authors: Budhathoki Nibash , Timilsina Sunita , Thomas Charles , Damato Aaron , Magid Diefenbach Catherine S. , Braunstein Marc Justin 
Published: May 2020

e20043 Background: MALTomas are extranodal marginal zone lymphomas that arise from B cells in various mucosal lymphoid tissue and are typically indolent. Patients with MALTomas may be at risk for additional cancers due to their long-term survival following treatment, however the incidence of SPM in MALTomas in the U.S. has not been previously described. Methods: Adults with MALT lymphoma were identified using the 2000-2016 SEER-18 database. SPM was defined as tumors diagnosed ≥6 months and up to x months from lymphoma diagnosis. SEER*stat was used to calculate SPM by multiple primary standardized incidence ratio based on observed (O) and expected (E) cases. The expected cases of new cancers of specific types were estimated by assuming that incidence rates for new primary tumors corresponded to sex, age, and calendar time–specific SEER rates for similar invasive primary cancers and applying those rates to the accumulated person-years (PYR) of observation. Excess absolute risk (EAR) of malignancy per 10,000 PYR at risk was calculated as ([O − E]/PYR) × 10,000. Results: As summarized in the table, 12,500 patients were diagnosed with MALT lymphoma of which 1466 (11.8%) developed 1626 SPMs (O/E rate 1.5, 95%CI 1.4-1.5, P < 0.001, EAR 70.4). Median latency period was 54 months (range 6 - 201). Non-Hodgkin lymphomas at separate tissue sites were the most common SPM, with 299 documented cases (O/E rate 6.2, 95%CI -5.4-6.8, P < 0.001, EAR 33.4). Between 6-24 months from MALToma diagnosis, head and neck, renal cell, liver, and anal cancers were increased, while after 24 months, gastric and small bowel cancers, CLL, ALL, and myeloma were increased compared to the general population of the same age group. Conclusions: There is distinct pattern of SPM among patients with MALT lymphoma in within and after 2 years from diagnosis, with an increased incidence compared to the general population. Consider the median latency, SPM may be due in part to the long-term survival and relatively older age of this population. [Table: see text]
Updated results of the ASPEN trial from a cohort of patients with MYD88 wild-type (MYD88WT) Waldenström macroglobulinemia (WM).
Authors: Garcia-Sanz Ramón , Dimopoulos Meletios A. , Lee Hui-Peng , Trneny Marek , Varettoni Marzia , Owen Roger G. , Castillo Jorge J. , Siddiqi Tanya , Tedeschi Alessandra , Buske Christian , Leblond Veronique , Chan Wai Y. , Schneider Jingjing , Ro Sunhee K. , Cohen Aileen , Huang Jane , Tam Constantine Si Lun 
Published: May 2020

e20056 Background: Inhibitors of Bruton tyrosine kinase (BTK) have shown significant activity in patients with WM harboring a mutation in the MYD88 gene. However, lower response rates and shorter progression-free survival have been reported in patients with WM who lack such mutations ( N Engl J Med. 2015;372:1430). The ASPEN trial evaluated zanubrutinib (ZANU), a potent and selective BTK inhibitor, in WM patients. Methods: In the ASPEN trial, bone marrow MYD88 mutations were assessed at study entry by a central laboratory (NeoGenomics). Based on the results of the MYD88 mutation assay, patients were assigned to cohort 1 ( MYD88 mutation) or cohort 2 ( MYD88WT or mutation unknown). All cohort 2 patients received ZANU 160 mg twice daily until disease progression. The objective was to assess the safety and efficacy of ZANU in patients with MYD88WT WM. Results: In total, 28 patients with 26 MYD88WT WM were enrolled into cohort 2. The median age was 72 years; 5 patients were treatment-naïve (TN) and 23 patients were relapsed/refractory (R/R; ≥1 prior therapy). Most patients had intermediate- (39.3%) or high-risk (42.9%) disease by International Prognostic Scoring System for WM. With the median follow-up of 17.9 months, 2 patients discontinued ZANU due to adverse events, and 6 patients experienced disease progression; there were no cases of disease transformation. The overall response rate was 80.8%, with a major response rate of 50.0%, including a very good partial response (VGPR) rate of 26.9% (Table). Progression-free survival event-free rate at 12 months was 72.4%. The most frequently reported adverse events (AEs) were diarrhea, anemia, contusion, pyrexia, and upper respiratory tract infection. Major hemorrhage was reported in 2 patients, and atrial fibrillation was reported in 1 patient. There were no fatal AEs. Conclusions: ZANU showed clinically meaningful antitumor activity, including achieving major responses and durability of responses, and was considered well-tolerated with a low discontinuation rate due to AEs, in patients with MYD88WT WM. ZANU demonstrated efficacy regardless of MYD88 mutational status in WM. Clinical trial information: NCT03053440 . [Table: see text]
Health-related quality of life (HRQOL) burden in patients with relapsed/refractory diffuse large B-cell lymphoma (RR-DLBCL) and non-Hodgkin’s lymphoma (RR-NHL).
Authors: Lin Vincent , Oak Bhagyashree , Snider Julia , Epstein Josh 
Published: May 2020

e20070 Background: CAR T therapy is being investigated as 2nd line therapy in RR-DLBCL. To evaluate its impact on patients’ HRQOL, it is essential to understand the HRQOL of patients receiving current standard of care (SOC) therapy for DLBCL and NHL patients. Methods: A systematic literature review (SLR) of studies reporting HRQOL in RR-DLBCL patients was conducted in March 2019 (updated to include RR-NHL in May 2019) using EMBASE, MEDLINE, Cochrane (all from 2007), Northern Light and International Society for Quality of Life Research abstracts (both from 2017). A targeted literature review (TLR) for untreated or 1st line patients was conducted in July 2019 using PubMed. Search terms included diseases, lines of therapy and patient-reported outcome (PRO) measures. Abstracts and publications were screened for eligibility and data were extracted. Results: Of the 977 publications screened for the SLR, 26 met the inclusion criteria. Another 18 studies were included from the TLR. The most commonly used PRO measures were the SF-36 (10 studies), EORTC QLQ-C30 and FACT-Lym (8 studies each). The EORTC QLQ-C30 showed statistically significant or clinically meaningful changes in a greater number of domains (86%) than the FACT-Lym (75%) and SF-36 (62%). Additional results in table. Conclusions: While research is limited, RR-DLBCL patients receiving current SOC therapy report decreases in HRQOL and health utility. Further research is needed on how existing and future therapies may affect HRQOL among RR-DLBCL patients. [Table: see text]