bluuebunny/crossref_metadata_2025_split huggingface dataset:
Durability of complete response after blinatumomab therapy for refractory/relapsed aggressive B-cell non-Hodgkin lymphoma.
Authors: Viardot Andreas , Hess Georg , Bargou Ralf C. , Morley Nicholas , Gritti Giuseppe , Iskander Karim , Cohan David , Zhang Alicia , Franklin Janet , Coyle Luke 
Published: March 2020

e19041 Background: Achieving durable response in patients (pts) with relapsed/refractory (R/R) aggressive B-cell lymphoma (B-NHL) is challenging. Blinatumomab, a bispecific T-cell engager (BiTE) immunotherapy targeting CD19-expressing cancer cells, has shown promising efficacy in pts with R/R aggressive B-NHL. We report the durability of complete response (DOCR) in pts treated with blinatumomab. Methods: The DOCR in pts with R/R aggressive B-NHL responding to blinatumomab was assessed using data from two phase 2 studies (study 1 [N = 25], NCT01741792; study 2 [N = 41], NCT02910063) in pts with R/R aggressive B-NHL. CR was assessed using Cheson (study 1) and Lugano (study 2) criteria. Time-to-event variables were analyzed using the Kaplan-Meier (KM) method. Results: Baseline pt characteristics in the pooled analysis were: median age 59 years (range, 4177); 54% men; 54% treatment refractory; median 2 lines of prior therapy (range, 17); and 15% with prior autologous hematopoietic stem cell transplant. Of 25 pts treated with blinatumomab in study 1, 4 (16%) evaluable pts achieved CR. Of 41 pts treated with blinatumomab in study 2, 9 (22%) achieved CR. Median DOCR was not reached (Table). At a median follow-up of 9.1 months in the pooled analysis, 3 pts (23%) had relapsed (study 1, n = 2 [50%]; study 2, n = 1 [11%]). At 12 and 18 months, the KM probability of maintaining CR in the pooled analysis was 53.0% (95% confidence interval [CI], 8.5, 85.0). Conclusions: For pts with R/R aggressive B-NHL who received blinatumomab, a durable response is possible. Longer-term follow up is needed to fully characterize the DOCR to blinatumomab. Clinical trial information: NCT01741792; NCT02910063. [Table: see text]
A core laboratory approach to large-scale radiomics and machine-learning prediction of DLBCL outcomes after first-line treatment using results from the phase III GOYA study.
Authors: Chauvie Stephane , Dalmasso Federico , Pierce Larry , Nielsen Tina , Sahin Deniz , Lee Calvin , Mattiello Federico , Kostakoglu Lale , Kinahan Paul 
Published: March 2020

e19042 Background: We are using the phase 3 GOYA study to retrospectively investigate using quantitative image texture features (i.e. radiomics, evaluating tumor heterogeneity) to improve the prognostic value of baseline FDG-PET. We report on the considerations for analysis, which is ongoing, and solutions to methodological challenges. Methods: GOYA, an open-label, randomized, phase 3 study, enrolled 1418 patients from 207 centers; 1334 had a baseline FDG-PET scan with detectable lesions. Image data with annotated regions of interest (ROIs) defined by qualified physicians were transferred to the Cuneo imaging core laboratory. Images were interpolated to a common 4x4x4 mm voxel size and ROI masks using 4 different definition methodologies were used to define image sub-volumes that contained the lesions. Large ROIs in normal liver were also defined. The 42 Haralick radiomic image texture features were computed using the PET oncology radiomics test suite. Results: A total of 9286 lesions were analyzed. Interpolation of images to a fixed size is challenging in this cohort due the large number of features to be computed (~1.5M). As a test, the lesions were differentiated from liver ROIs using 5 classifiers (e.g. support vector machine, random forest, etc) with an accuracy of 0.995–0.999. The mean (±SD) of the metabolically active tumor volume was 21.2±22.2 mL (range 0.2–146 mL) with a preponderance of smaller lesions as shown by the median of 15.0 mL. The skewed distribution had downstream effects on many of the quantitative (e.g. total lesion glycolysis) and radiomic image texture features. The majority of texture features were computable; 5 (Coarseness, Contrast, Busyness, Complexity, Texture Strength) required interpolation to a 2x2x2 mm voxel size, requiring extended computation time. FDG-PET images came from a variety of PET/CT scanners; thus, a unified image reconstruction protocol was not possible. Conclusions: Radiomics analysis of large phase 3 imaging trials is feasible. However, careful attention should be paid to the entire processing chain, including tests for non-computable features values due to highly skewed distributions and lesion size. Clinical trial information: NCT01287741.
SYK inhibition with fostamatinib in Waldenström's macroglobulinemia: In vitro cell based assays.
Authors: Markovtsov Vadim , Masuda Esteban 
Published: March 2020

e19047 Background: Waldenström's macroglobulinemia (WM) is characterized by accumulation of IgM secreting neoplastic B cells in the bone marrow (BM). B-cell antigen receptor (BCR) signaling plays a pivotal role in the regulation of integrin-mediated retention of lymphoma cells in the BM. Signaling through the BCR leads to activation of spleen tyrosine kinase (SYK) and downstream kinases which play a role in lymphoma pathobiology. The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib targets BCR-controlled signaling and integrin-mediated adhesion in WM cells, but patients with WM may become refractory to ibrutinib treatment. As SYK signaling is upstream of BTK, we explored the effect of the SYK inhibitor R406 (the active metabolite of fostamatinib) on BCR mediated signaling and cell adhesion in WM. Methods: MWCL-1 cells were treated with R406, CAL101 (PI3 kinase inhibitor) or ibrutinib at concentrations up to 10µM and stimulated with anti-IgM antibodies or PMA. The cells were transferred to plates coated with fibronectin to assess cell adhesion. For the proliferation assays, MWCL-1 cells or primary B cells were pretreated with kinase inhibitors, followed by stimulation of primary B cells with anti-IgM. Results: Anti-IgM or PMA alone stimulated the adhesion of MWCL-1 on fibronectin. The addition of R406 had a comparable effect to ibrutinib on inhibition of IgM mediated cell adhesion (IC50 = 0.32µM), consistent with the effect of both compounds on BCR mediated signaling. Neither compound affected PMA induced cell adhesion, indicating that the effect on IgM mediated cell adhesion was not due to toxicity. Lack of off-target toxicity was further confirmed in the MWCL-1 proliferation assays where the compounds showed less potency than in BCR-mediated assays. Comparable inhibition of adhesion and proliferation was seen with CAL101. Conclusions: Preliminary preclinical studies with R406 show that SYK is involved in BCR mediated signaling and cell adhesion in WM. CAL101 mediated inhibition of adhesion further confirmed the role of SYK, which is upstream of PI3K. R406 was as effective as ibrutinib in blocking WM cell adhesion. Further studies of SYK inhibition with fostamatinib as a potential treatment option for WM are warranted.
Cost-Effectiveness of brentuximab vedotin with chemotherapy in frontline treatment of CD30-expressing peripheral T-cell lymphoma.
Authors: Feldman Tatyana , Zou Denise , Rebeira Mayvis , Lee Joseph , Harris Mack , Ma Wenkang , Fanale Michelle A. , Manley Thomas John , Feliciano Joseph , Rao Shangbang , Kansal Anuraag 
Published: March 2020

e19060 Background: The most common frontline treatment for peripheral T-cell lymphoma (PTCL) is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or a CHOP-like regimen. In the recently reported phase 3 ECHELON-2 trial, brentuximab vedotin (BV) in combination with CHP (A+CHP) demonstrated significant improvement in progression-free survival (PFS) and overall survival (OS) compared to CHOP, with a manageable safety profile. The objective of this analysis was to evaluate the cost-effectiveness of A+CHP in the frontline setting for CD30-expressing PTCL. Methods: A partitioned survival model consisting of 3 health states (PFS, post progression survival, and death), was constructed using clinical and quality of life data from ECHELON-2 from a US payer perspective over a lifetime time horizon. PFS and OS observed from ECHELON-2 were extrapolated using standard parametric distributions. The best-fitting distributions (log-normal for both arms) were selected based on statistical goodness of fit and clinical plausibility of the long-term projections. Health utilities were derived from the European Quality of Life 5-Dimensions (EQ-5D) data collected in ECHELON-2. The average utility scores for the pre- and post-progression periods were estimated via a repeated-measures mixed-effects model. Medical resource use and costs were from literature. Results: The model predicted A+CHP extended undiscounted PFS by 2.92 and OS by 3.38 years over CHOP. These survival gains drive the value in the model. After adjusting for quality of life and discounting, A+CHP was associated with 1.79 quality-adjusted life years (QALYs) gained at an incremental cost of $176,842, yielding an incremental cost-effectiveness ratio (ICER) of $98,987. Sensitivity analyses of alternative model assumptions provided ICERs from $64,000 to $154,000. The estimated probability that A+CHP is cost-effective compared with CHOP was 75% at a willingness-to-pay threshold of $150,000. Conclusions: Based on the ECHELON-2 trial data, this analysis showed for patients with previously untreated CD30-expressing PTCL, treatment with BV in combination with CHP is likely to be cost-effective in comparison to CHOP.
GX-G3, a long-acting G-CSF, compared with pegfilgrastim in reducing duration of severe neutropenia after chemotherapy for non-Hodgkin’s lymphoma.
Authors: Ertan-Ahmed Senem , Kiehl Michael G. , Radinoff Atanas , Graklanov Vasko , Tzvetkov Nikolay , Mihăescu Rodica , Özatlı Düzgün , Atalay Figen , Turgut Burhan , Cho Seok-Gu , Rekhtman Grygoriy , Sahin Adem , Oncel Hatice , Choi Yuri , Yang Sang-In , Choi Yoon-Jeong , Heo MinKyu , Sung Young Chul 
Published: March 2020

e19065 Background: G-CSF is used in patients at significant risk for developing severe neutropenia (neutrophil count < 0.5 × 109/L or grade 4 neutropenia) following myelosuppresive chemotherapy. GX-G3, human G-CSF fused to hyFc is a proposed alternative to Neulasta. Methods: An open-label, randomized, phase II study was designed to compare the effects of subcutaneous (SC) injection of GX-G3 (a long-acting G-CSF) at doses of 150, 250 and 350 μg/kg with Neulasta 6 mg administered SC in patients receiving R-CHOP for advanced NHL (n = 65). The primary objective was to assess the duration of severe neutropenia after 1st cycle of chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP). The following parameters were also assessed: duration of severe neutropenia after 2nd cycle of chemotherapy, optimal time for GX-G3 intervention (two GX-G3 250 μg/kg cohorts; administered 24 and 72 hours after R-CHOP), incidence of severe neutropenia and febrile neutropenia post R-CHOP, pharmacokinetics, and safety. Patients were randomly assigned to receive GX-G3 or reference drug, Neulasta, one dose after 1st and 2nd cycle of R-CHOP for a total of 2 doses. Results: The mean duration of severe neutropenia after 1st cycle was shortest in GX-G3 350 μg/kg group [GX-G3 150, 250 (24h, 72h), 350 μg/kg and Neulasta®; 3.2, 2.3, 2.0, 1.3 and 2.4 days, respectively]. The results of all GX-G3 groups and Neulasta were not significantly different for duration of severe neutropenia after 2nd cycle of R-CHOP, incidence of severe neutropenia and febrile neutropenia, or toxicity profile. The elimination half-life of GX-G3 and Neulasta ranged from 29.8 to 66 hours and 19.2 to 76.8 hours, respectively. Conclusions: GX-G3, in all tested dosage regimen, was safe and well tolerated in this patient population. A single injection of GX-G3 per chemotherapy cycle provided neutrophil support with safety and efficacy similar to that provided by Neulasta. GX-G3 administration after 24 hours, compared to 72 hours post R-CHOP treatment resulted in relatively shorter duration of severe neutropenia. Clinical trial information: 2015-002693-20.
Post-transplant lymphoproliferative disorder-related admissions in the United States.
Authors: Yu Arlene , Acharya Prakash , Singh Seema , Durdevic Momcilo , Stan Andreea , Nimkar Abhishek , Elenius Henrik , Jesmajian Stephen , Naaraayan Ashutossh 
Published: March 2020

e19071 Background: Post-transplant lymphoproliferative disorders (PTLD) is an immunosuppression-related malignancy complicating solid organ transplant (SOT) and non-solid organ transplant (NSOT) (peripheral stem cell and bone marrow transplant). The epidemiology of PTLD-related hospital admissions (PRA) is unclear. The objective of our study is to describe the trend and outcomes of PRA in the United States. Methods: A descriptive, retrospective study was conducted using the National Inpatient Sample database from 2009-2014. PRA were selected using International Classification of Diseases-Ninth Revision, Clinical Modification diagnosis code (238.77). Multivariate regression analysis was performed to determine mortality and length of stay (LOS) in PRA. Results: The incidence of PRA in transplant-related hospital admissions was 7.19 per thousand admissions (pta) in 2009 and 7.24 pta in 2014 with annual percentage change (APC) of 0.1% (p = 0.9). The median age of patients with PRA was 47 (25-75 percentile: 19-61) years, 38.8% were females, 69.9% were white and 10.7% were African-American. Among patients with PRA, 91.1% had SOT [kidney (31.4%), liver (20.9%), heart (14.6%), lung (7%) and small intestines (1.89%)]; 7.1% had NSOT [bone marrow (3.9%) and peripheral stem cell (2%)] and 1.8% had two or more organ transplants. The most common principal diagnosis in PRA were complications of organ transplant (33.3%), encounter for anti-neoplastic chemotherapy (11.4%), neutropenia (5%), acute kidney injury (3.7%) and hearing loss (1.7%). Among transplant-related hospital admissions, PRA had higher adjusted odds of inpatient mortality [Odds ratio (OR) 2.57 (Confidence Interval (CI) 1.69-2.42), p < 0.001] and longer LOS [4.22 days (CI 3.26-5.17), p < 0.001] than non-PRA. Among PRA, those with NSOT have higher adjusted odds of mortality [OR 2.98 (CI 1.07-8.29), p = 0.036] and longer LOS [16.27 days (CI 3.51-29.03), p < 0.013] compared to those with SOT. Conclusions: PRA have higher odds of mortality and longer LOS compared to other transplant-related hospital admissions. Even though SOT accounts for most of the PRA, the adjusted odds of mortality are significantly higher in PRA with NSOT.
Clinical and cytogenetic features of nonsecretory multiple myeloma (NSMM) in the era of novel agent induction therapy: The Mayo Clinic experience.
Authors: Nandakumar Bharat , Gonsalves Wilson I. , Buadi Francis , Dispenzieri Angela , Dingli David , Lacy Martha , Kapoor Prashant , Lin Yi , Kourelis Taxiarchis , Muchtar Eli , Go Ronald S. , Warsame Rahma M. , Hayman Suzanne R. , Leung Nelson , Hwa Lisa , Fonder Amie L. , Kyle Robert A. , Gertz Morie A. , Rajkumar S. Vincent , Kumar Shaji 
Published: March 2020

e19519 Background: NSMM is a rare subtype of myeloma that has not been well characterized in the era of novel agent induction therapy. Thus, we evaluated the clinical and cytogenetic features of patients with newly diagnosed NSMM evaluated at our institution. Methods: We evaluated all NSMM patients seen at the Mayo Clinic, Rochester from 2008-2017 based on the absence of a detectable monoclonal protein in their serum and urine electrophoresis and having a concurrent involved serum immunoglobulin light chain of less than 5 mg/dL. Survival analysis was performed by the Kaplan-Meier method and clinical and cytogenetic features were reported descriptively. Results: This cohort consisted of 30 consecutive patients with NSMM with a median age of 62 years (40-79) of which 16 (53%) were male. The median bone marrow plasma cell involvement was 70% (Range: 0 – 100). There were 3/25 (12%) patients who presented with a creatinine of 2 mg/dL or greater and 6/23 (26%) patients who presented with hypercalcemia (11 mg/dL or greater). The ISS classification of this cohort is as follows: Stage 1- 8 (36%) patients, Stage 2- 3 (14%) patients and Stage 3- 11 (50%) patients. There were 6 (21%) out of 28 patients with high risk cytogenetics (either del 17p, t(4;14), t(14;16) or t(14;20). The distribution of primary cytogenetic abnormalities among this cohort was as follows: t(11;14) – 16 (57%), t(4;14) – 1 (4%), trisomies – 6 (21%) and other - 5 (13%). The median overall survival (OS) for patients in this cohort was 59 months (95% CI: 34 – 64). In comparison to a control cohort of newly diagnosed secretory myeloma patients matched for age, gender and year of diagnosis in a 1:2 ratio, the median OS was worse for the NSMM cohort but this was not statistically significant (59 vs. 92 months, p = 0.257). Conclusions: Patients diagnosed with NSMM had a predisposition towards having a t(11;14) primary cytogenetic abnormality. In the era of novel agent induction therapy, they may have a survival outcome that may be worse than newly diagnosed secretory myeloma patients.
Can autologous stem cell transplantation abrogate the poor prognosis associated with high LDH in myeloma patients?
Authors: Ilhan Osman , Cengiz Seval Guldane , Toprak Selami Kocak , Civriz Bozdag Sinem , Yuksel Meltem Kurt , Topcuoglu Pervin , Arslan Onder , Ozcan Muhit , Demirer Taner , Akan Hamdi , Beksac Meral , Gurman Gunhan 
Published: March 2020

e19524 Background: Multiple myeloma (MM) is a plasma cell neoplasia characterized by a diffuse clonal plasma cell infiltration of the bone marrow. Serum lactate dehydrogenase (LDH) is a relevant biomarker in MM and in the era of novel agents, LDH confirmed its negative impact on survival in newly diagnosed setting (Bal et al., presented at ASH2018). Methods: This single center retrospective study included 208 patients with a diagnosis of MM who underwent ASCT at our center between January 2008 - Mart 2018 were prospectively analyzed. We identified patients with baseline serum LDH values (ULN = 247 U/L). We compare baseline characteristics and outcomes of ASCT according to LDH values. Results: All clinical data were available in 208 cases (High LDH: 92 (44.2%), Normal LDH: 116 (55.8%)) There were 87 (41.8 %) female and 87 (41.8 %) male patients. The median age at diagnosis of MM was 63 years (range, 37-77 years). The median time of follow-up was 48 months (range, 2.8-197.5 months). Of the 92 patients with high LDH who underwent ASCT, median age was 65 years and ECOG performance status was 1 and 58.6 % were male. There was no statistically differences in performance status, induction treatment regimens and the number of treatment line prior to ASCT. Induction therapy consisted of 3 drugs in 91.3% and 2 drugs in 8.7 % in high LDH group (p = NS). Forty-eight (53.3%) patients with high LDH received a bortezomib-based induction and 35 patients (40.2 %) achieved ³ very good partial remission (VGPR) after the induction therapy. During follow up, 45 relapses were occurred and all relapsed patients died. According to the long-rank test, estimated 5-year OS was not significantly different between normal and high LDH categories (63.3 %±0.6 % vs. 64.6 %±0.5 %; p = 0.99). Median PFS was 101.4 months (95% CI: 73.7-129) in high LDH group and 92.1 months (95% CI: 71.1-113.1) in normal LDH group (p = 0.99). Conclusions: Elevated LDH was confirmed as a poor prognostic factor in previous reports. In our transplanted patients with high LDH cohort, clinical outcomes are favorable and similar those have normal LDH. Therefore, further studies of larger randomized cohorts are required to clarify the impact of pre-transplant LDH levels on ASCT outcomes.
Treatment patterns and outcomes among t(11;14) myeloma patients in a real-world setting.
Authors: Norden Andrew David , Mathura Shivam , Hansen Eric , Goldberg Stuart L. , Siegel David Samuel DiCapua 
Published: March 2020

e19531 Background: There is uncertainty about the prognostic and predictive significance of t(11;14), long considered a standard risk cytogenetic abnormality in multiple myeloma (MM). This translocation is associated with elevated BCL-2 expression which may explain responses to venetoclax that have been reported previously. In a real-world database derived from EMR data, we sought to characterize real-world treatment patterns and outcomes from this unique MM cohort. Methods: Records for MM patients with t(11;14) diagnosed between 2000 and 2017 were identified in the COTA real-world database. Descriptive statistics were used to summarize the data. Results: 399 MM patients with t(11;14) were identified. Patient characteristics are summarized in the Table. The most frequent first-line treatments were bortezomib + dexamethasone + lenalidomide (134, 33.6%), bortezomib + cyclophosphamide + dexamethasone (69, 17.3%), and bortezomib + dexamethasone (60, 15.0%). Six (1.5%) patients received venetoclax. Response and progression-free survival data are being analyzed and will be presented at the meeting. Median overall survival was 14.3 (95% CI 10.4 – not yet reached) years. Conclusions: Real-world databases are useful in describing treatment patterns and outcomes in narrowly defined cohorts such as MM with t(11;14). The OS result reported here is unexpectedly long and will be fully explored prior to presentation. [Table: see text]
Pretransplant hemoglobin and serum creatinine levels correlate with progression free survival in myeloma patients undergoing autologous stem cell transplantation.
Authors: Demirer Taner , Cengiz Seval Guldane , Toprak Selami Kocak , Civriz Bozdag Sinem , Yuksel Meltem Kurt , Topcuoglu Pervin , Arslan Onder , Ozcan Muhit , Akan Hamdi , Ilhan Osman , Beksac Meral , Gurman Gunhan 
Published: March 2020

e19532 Background: High dose melphalan and autologous stem cell transplantation (ASCT) significantly prolong survival for patients with multiple myeloma (MM). The purpose of this study is to assess the effects of hemoglobin (Hgb) and serum creatinine (Crea) values at the time of transplantation on the overall outcome of patients with multiple myeloma treated at our transplant center. Material & Methods: This analysis included 247 consecutive patients who underwent ASCT for MM between 2010-2016. Hemoglobin was grouped as low or high relative to their sample median. Patients were also stratified according to serum Crea value at the time of transplantation ( < 2 or ³2 mg/dl). Results: The median age was 57 (29-75) years and most patients were male (n = 151, 61.1%), IgG subtype (n = 124, 50.2%), and ISS stage 3 (n = 122, 49.4%). The interval from the time of diagnosis to ASCT was median 7 months and median follow-up from ASCT was 49 months (range, 3-198 months). The most commonly induction regimens included VAD (vincristine, doxorubicin and dexamethasone) and VCD (bortezomib, cyclophosphamide, dexamethasone), respectively. Since maintenance was not an approved treatment in myeloma most patients did not receive any. For the entire cohort, the median Hgb and Crea were 11.5 g/dL and 0.9 mg/dL respectively. No difference in progression free survival (PFS) was observed between a lower and higher Hgb (82 vs. 81 months, p = 0.96). However, the median PFS was significantly longer in patients with a lower Crea compared to those with a higher Crea (83 vs. 48 months, p = 0.01). Patients with both a lower hemoglobin and higher Crea experienced shorter PFS compared to those with a higher hemoglobin and lower Crea (45 vs. 82 months, p < 0.001). We failed to demonstrate the impact of creatinin levels on time to neutrophil and platelet engraftment. There were no differences in OS according to lower vs. higher Hgb (58 vs. 52 months; p = 0.29, respectively) but in higher crea cohort worse OS was observed (41 months vs. 57 months; p = 0.02, respectively). Conclusions: We demonstrate that hemoglobin and creatinine represent important determinants of clinical outcomes after ASCT. A lower hemoglobin and higher creatinine, individually and when combined, were associated with shorter PFS. Therefore, further studies of larger randomized cohorts are required to clarify the impact of pre-transplant Hgb and Crea levels on ASCT outcomes.