bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of a screening program for identification of unrecognized inherited marrow failure syndromes.
Authors: Lachowiez Curtis Andrew , Meyers Gabrielle 
Published: September 2018

7055 Background: Inherited marrow failure syndromes (IMFS) are considered diseases of childhood, but testing adults with atypical presentations of diseases associated with IMFS is critical for establishing an optimal treatment protocol. The most common IMFS, Fanconi Anemia and Telomere Biology Diseases, are associated with MDS and aplastic anemia (AA), head and neck cancers, skin, and cervical cancer. Such patients can have profound toxicity with standard chemotherapy regimens. Methods: We implemented a screening protocol in patients at highest risk of an undiagnosed IMFS (MDS under age 60, AA patients under age 65, and head and neck cancers under age 60) with chromosome breakage analysis and telomere length testing. Results: Our protocol diagnosed nine patients (estimated ~10% of patients < age 60 with these diseases) with IMFS. The features of these patients are described in the table. Only three (33%) patients had the classic physical characteristics of IMFS. Three patients were over age 50 when diagnosed with an inherited disorder. Most importantly, in all patients the treatment approach was modified significantly, including minimizing conditioning for BMT, utilizing danazol as first line treatment for AA, as well as aggressive cancer and endocrinopathy screening. Outcomes with modified treatment have been favorable, and occult malignancies were detected through screening in two patients. Conclusions: Inherited marrow failure syndromes are uncommon yet under recognized disorders that significantly impact treatment decisions in addition to implementation of surveillance programs for both the affected individual and their relatives alike. Through this approach of thoughtful screening of patients presenting to our institution with marrow failure we identified an unrecognized IMFS in an estimated 10% of patients. [Table: see text]
A genetic risk-stratified, randomized phase 2 intergroup study of fludarabine/antibody combinations in symptomatic, untreated chronic lymphocytic leukemia (CLL): Results from Cancer and Leukemia Group B (CALGB) 10404 (Alliance).
Authors: Ruppert Amy S. , Byrd John C. , Heerema Nyla A. , Smith Mitchell Reed , Godwin John E. , Couban Stephen , Fehniger Todd A. , Thirman Michael , Halvorson Alese E. , Tallman Martin S. , Appelbaum Frederick R. , Stone Richard M. , Robinson Sue , Chang Julie E. , Mandrekar Sumithra J. , Larson Richard A. 
Published: September 2018

7503 Background: Prior to use of novel targeted agents for CLL, debate existed regarding the best chemoimmunotherapy regimen to build upon in patients (pts) with non-del(11q) disease. The role of lenalidomide (L) was also not defined. CALGB 10404 was a randomized phase 2 study addressing these questions. Methods: Pts with untreated CLL requiring therapy were randomized to treatment with fludarabine + rituximab (FR), FR + 6 monthly consolidative treatments of L (5 mg days 1-21/28 x 1 then 10 mg days 1-21/28 x 5) (FR+L), or FR + cyclophosphamide (FCR). Based on pretreatment central interphase cytogenetic screening, pts with del(11q22.3) in at least 20% of cells were excluded from the primary analysis, testing whether 2-year progression-free survival (PFS) rate was improved in non-del(11q) pts within each arm. A target accrual of 103 non-del(11q) pts per arm provided at least 84% power to detect an increase in 2-year PFS rate from 60% to 73%; the critical value was 69% using a single stage design and type I error rate of 4%. Results: A total of 342 non-del(11q) CLL pts were randomized to treatment with FR (n = 123), FR+L (n = 109), or FCR (n = 110). Baseline characteristics were similar across arms. Two-year PFS rates with exact 90% CIs were 64% (57-71%) (FR), 71% (63-78%) (FR+L), and 74% (66-80%) (FCR). Median PFS was significantly shorter with FR compared to FR+L (p = 0.03) and FCR (p < 0.01): 43 (95% CI: 33-50), 66 (95% CI: 45-not reached), and 78 (95% CI: 58-not reached) months respectively. Median overall survival (OS) has not been reached for any arm. OS at 1, 2, and 3 years was similar across arms, although there was a plateau in OS with no events beyond 41 months in the FR+L arm, different from FR/FCR where events continued to occur. The most common adverse events were cytopenias and infections. Conclusions: FR+L and FCR met the protocol defined primary endpoint. FR+L extended PFS relative to FR and a plateau in survival differentiated this arm from the FR/FCR arms. Future studies comparing FR+L to FCR or incorporating L into other novel treatment regimens are justified. Support: U10CA180821, U10CA180882, Celgene. Clinical trial information: NCT00602459.
Autologous (auto) versus matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic (allo) hematopoietic cell transplantation (HCT) in follicular lymphoma (FL) patients (pts) with early chemoimmunotherapy failure (ECF): A Center for International Blood and Marrow Transplant Research (CIBMTR) analysis.
Authors: Godfrey James K. , Smith Sonali M. , Ahn Kwang Woo , Digilio Alyssa , Fenske Timothy S , Sureda Anna M. , Hamadani Mehdi 
Published: September 2018

7508 Background: Contrary to most FL, high-risk FL pts with ECF (i.e. relapse within 2 yrs of frontline chemoimmunotherapy) have a 5 yr OS of only 50%. (Casulo, JCO 2015). We used the CIBMTR database to compare autoHCT versus either MSD or MUD alloHCT as the first transplant approach in FL pts with ECF. Methods: Adult FL pts (age ≥18) undergoing autoHCT or alloHCT between 2002-2014 and receiving first line rituximab-based chemoimmunotherapies with evidence of ECF (defined as disease relapse or progression within 2 yrs of treatment initiation) were included. The primary endpoint was OS; secondary endpoints were progression-free survival (PFS), relapse and non-relapse mortality (NRM). Results: 440 pts had ECF (auto = 240, MSD = 105, MUD = 95) (Table 1). The 5 yr adjusted probabilities (AjP) of NRM were significantly lower with autoHCT (5%), versus MSD (17%) or MUD (33%) HCT (p<0.0001). 5 yr AjP of relapse were significantly lower with MSD (31%) or MUD HCT (23%), versus autoHCT (58%; p<0.0001). AjP of 5 yr PFS following auto, MSD and MUD HCT were 38%, 52% and 43% (p=.006) respectively. The AjP of 5 yr OS was significantly higher following autoHCT (70%) or MSD HCT (73%) versus MUD HCT (49%; p=0.004). Conclusions: AutoHCT for FL pts with ECF has low NRM and 5 yr OS rates (70%) that are provocatively higher than historical data (~50%). MSD HCT had the lowest relapse rate with similar survival. A prospective trial confirming the role of HCT in ECF FL is warranted. [Table: see text]
Tolerability and activity of chemo-free triplet combination of TGR-1202, ublituximab, and ibrutinib in patients with advanced CLL and NHL.
Authors: Nastoupil Loretta J. , Lunning Matthew Alexander , Vose Julie , Schreeder Marshall T. , Siddiqi Tanya , Flowers Christopher , Cohen Jonathon Brett , Burger Jan Andreas , Wierda William G. , O'Brien Susan Mary , Sportelli Peter , Miskin Hari P. , Purdom Michelle A , Weiss Michael S. , Fowler Nathan Hale 
Published: September 2018

7511 Background: Novel targeted agents are emerging for B-cell malignancies, but few studies have safely combined these agents. Ublituximab (UTX) is a novel glycoengineered mAb targeting a unique epitope on the CD20 antigen. TGR-1202 is a next generation, once daily PI3Kδ inhibitor, demonstrating a favorable safety profile compared to prior inhibitors, including in long-term follow up (Burris, 2016). This Ph 1 trial evaluates the safety/efficacy of the triplet combination of a novel anti-CD20 mAb + PI3Kδ + BTK inhibitor (ibrutinib) in pts with B-cell malignancies. Methods: Eligible pts had CLL or rel/ref NHL w/o limit to prior therapies, including those ref to prior PI3Kδ or BTK inhibitors. UTX dosed on D1, 8, 15 of C1; D1 of C2-6, and C9 & 12. TGR-1202 dose escalated (400/600/800mg QD), ibrutinib dosed at 420mg (CLL) or 560mg (NHL), both on C1D1. Results: 38 pts were enrolled: 20 CLL/SLL and 18 NHL, including 6 follicular (FL), 6 DLBCL, 4 mantle cell (MCL) and 2 marginal zone (MZL). Med age 65 yrs (range 32-85); 29 M/9 F; med prior tx = 3 (range 0-6). 2 pts were ref to prior PI3Kδ and 2 were prev treated with ibrutinib (1 ref/1 rel). MTD was not reached. Most common ( > 20%) all causality AE’s were fatigue (42%), diarrhea (39%), dizziness (34%), nausea (32%), neutropenia, pyrexia, rash, infusion reaction, insomnia (each at 29%), thrombocytopenia, cough (each at 26%), anemia (24%) and sinusitis (21%). GR 3/4 AE’s were minimal, the only event > 10% was neutropenia (16%). ORR amongst 36 evaluable pts is shown in the table below. 53% of evaluable CLL pts had high-risk cytogenetics and 4/6 DLBCL pts were non-GCB. One CLL pt (17p/11q del) ref to both PI3Kδ and ibrutinib achieved a CR. Med time on study is 10 mos (range 1 – 27+ mos). Med DOR not reached (range 3 – 24+ mos). Conclusions: This is the first known triple combination of an anti-CD20 mAb + PI3Kδ + BTK inhibitor. The combination of UTX, TGR-1202, and ibrutinib has been well tolerated with activity observed across heavily pre-treated and high-risk B-cell malignancies. Expansion cohorts at the highest dose (800mg TGR-1202 + full dose ibrutinib) are underway. Future trials for the triplet are warranted. Clinical trial information: NCT02006485. [Table: see text]
Ibrutinib vs chlorambucil: Immunophenotypic and quantitative impacts on circulating immune cells in chronic lymphocytic leukemia (CLL).
Authors: Solman Isabelle , You Hana , Taylor Marlene , Dubovsky Jason A. , Kipps Thomas J. , Burger Jan Andreas , Lal Indu , Chang Betty Y. , James Danelle Frances , Hill John Stephen 
Published: September 2018

7524 Background: Ibrutinib (ibr), a first-in-class, once-daily inhibitor of Bruton’s tyrosine kinase, is indicated by FDA for treatment (Tx) of patients (pts) with CLL. Following the outcome of the RESONATE-2 trial, ibr was approved as the first chemotherapy-free Tx option for treatment-naïve (TN) pts. In this study, ibr reduced the risk of progression or death by 84% compared with chlorambucil (chl). To assess the impact of ibrutinib vs this traditional chemotherapeutic agent on the immune system, quantitative changes in circulating cells were studied throughout the first year of Tx. Methods: Immunophenotypic analyses were performed by flow cytometry on peripheral blood to assess lymphoid and myeloid cells of TN CLL pts who received 420 mg ibr once daily (n=50) or 0.5-0.8 mg/kg chl twice a month (n=30). Medians of statistically significant changes (p<0.05, Wilcoxon test) in absolute counts of 1-year paired samples (pre-dose vs 1-year) are reported. Results: Chl progressively reduced circulating B, T, NK, NKT cells, myeloid derived suppressor cells (MDSC), and monocytes by 69%-99%. All development stages of CD4+ and CD8+ T cells, except stem cell memory T cells (TSCM), decreased by 51%-90%. Regulatory T cells (Treg) and PD1+ T cells also decreased similarly; however, long-term activated T cells (TLA) were not impacted. On the other hand, ibr mainly reduced B cells (90%), MDSC (61%) and some T cells, specifically TLA, PD1+ T cells, Treg and effector T cells (27-52%). Naïve T cells, TSCM, central memory T cells and NK cells were spared throughout the full year of Tx. Classical monocytes were increased (+187%), while non-classical monocytes and intermediate monocytes remained relatively steady. Conclusions: Chl, a traditional chemotherapy, affected non-specifically most immune cell subsets in circulation, although surprisingly it did not affect TLA which have been reported as dysfunctional in CLL. Ibr represents a more targeted Tx approach than cytotoxic chemotherapy; essentially B cells, abnormal T subsets (TLA, PD1+T, Treg) and pro-tumor MDSCs were reduced. However, ibr preserved naïve T cells, NK cells and monocytes, which are important for mounting anti-tumor responses. Clinical trial information: NCT01722487.
Whole body diffusion-weighted MRI to predict treatment outcome after one cycle of immunochemotherapy in aggressive non-Hodgkin lymphoma.
Authors: De Paepe Katja , De Keyzer Frederik , Bechter Oliver , Van Keerberghen Ciska-Anne , Gheysens Olivier , Wolter Pascal , Dierickx Daan , Janssens Ann , Verhoef Gregor , Oyen Raymond , Vandecaveye Vincent 
Published: September 2018

7534 Background: Treatment adaptation based on early identification of non-Hodgkin lymphoma (NHL) patients not responding to therapy might improve survival. The role of interim fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) after 2-4 cycles of immunochemotherapy (ICT) herein is experimental as it renders false positive results, due to a rituximab-induced inflammatory response. Whole body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) was evaluated as a radiation-free imaging technique to predict treatment outcome in NHL after one cycle ICT (2-3 weeks). Methods: 47 patients with aggressive NHL (35 DLBCL,2 primary mediastinal BCL,3 unclassifiable BCL, 2 Burkitt,2 MCL, 2 peripheral TCL and 1 extranodal NK-TCL) were enrolled. All had baseline and interim WB-DWI/MRI, and end-of-treatment PET/CT; 39/47 had interim PET/CT. International prognostic index (IPI), immunohistochemical (IHC) markers Ki-67, Bcl-6 and Bcl-2 were evaluated for their predictive value. WB-DWI/MRI was assessed quantitatively with histogram analysis (high b-value signal intensity (SI) and apparent diffusion coefficient (ADC)). Patients were categorized as non-responder when lesions had decreased ADC or insufficient SI decrease between scans. Kaplan-Meier survival analysis was performed with log rank, Cox hazard ratio calculation and multivariate analysis. Outcome measure was disease-free-survival (DFS). Results: Median follow-up time was 43 months (4-70 months). 33 patients had complete remission (CR), 5 progression and 9 recurrent disease. WB-DWI/MRI predicted DFS correctly in 45/47 (96%) [log rank p<0.001; hazard ratio (HR) 52, (CI 95% 6-401)]; end-of-treatment PET/CT was correct in 37/47 (79%) [p=0.003;HR 4.3, (1.5-12.4)], and interim PET/CT in 28/39 (72%) [p=0.016;HR 3.9, (1.2-12.5)]. IPI score and IHC parameters were not significantly predictive. Multivariate analysis showed WB-DWI/MRI as the only independent prognostic factor (p<0.001). Conclusions: WB-DWI/MRI can accurately predict treatment outcome in aggressive NHL after only one cycle of immunochemotherapy without the burden of radiation exposure. Clinical trial information: NCT01231269.
Phase II clinical trial of first-line combination of radiation followed by gemcitabine, dexamethasone, and cisplatin (GDP) chemotherapy for early-stage extranodal natural killer/T-cell lymphoma with unfavorable prognostic factors: The GREEN study (NCT02276248).
Authors: Qi Fei , Wang Wei-Hu , Li Ye-Xiong , Dong Mei , He Xiao-hui , Yang Jianliang , Yang Sheng , Fang Hui , Chen Bo , Qi Shunan , Qin Yan , Zhao Yuting 
Published: September 2018

7540 Background: Currently concomitant or sequential chemotherapy with radiotherapy has been recognized as the standard treatment for extranodal natural killer/T-cell lymphoma, nasal type (ENKTL). However, the optimal schedule has not been fully defined. Methods: We designed a phase II prospective study to investigate the efficacy and toxicity profile of sequential radiation followed by systemic GDP (gemcitabine, dexamethasone and cisplatin) chemotherapy on previously untreated early-staged (stage IE/IIE) ENKTL patients with at least one unfavorable prognostic factor. The primary endpoint was 2-year progression-free survival (PFS). Secondary endpoints were 2-year overall survival (OS), overall response rate (ORR), and toxicity. Results: A total of40 patients were enrolled and completed the entire course of treatment between June 2010 and June 2014. The median age was 38 (range 25-63) years old. All the enrolled patients presented with at least one unfavorable prognostic feature: age > 60 years (5.0%), B symptom (40%), elevated serum LDH (40.0%), regional lymph node involvement (32.5%) and primary tumor invasion (87.5%). At the completion of the whole treatment, ORR was 97.5% and the complete remission rate was 95.0%. Median follow-up time was 43.7 months (range 9.4-72.3 months). 2-, 3-, 5-year PFS rates were 84.7%, 82.1%, 77.5%, and OS rates were 89.9%, 87.1%, 79.7%, respectively. Recurrence within the RT field was observed in four patients and systemic failure in three individuals. Grade 1-2 skin reaction and mucositis were the main toxicity related to radiation. Grade 3-4 neutropenia (12/40), thrombocytopenia (7/40) and anemia (2/40) were observed during GDP chemotherapy. No clinically significant late toxicities were observed during follow-up visits. Conclusions: The current results indicates that first-line radiation followed by GDP chemotherapy can be one of the most effective and feasible treatment schedule for early-stage ENKTL patients, especially those with poor prognostic factors. Clinical trial information: NCT02276248.
MYC+ relapsed and refractory (R/R) diffuse large b-cell lymphoma (DLBCL): Impact of additional hits and outcomes with subsequent therapy.
Authors: Epperla Narendranath , Maddocks Kami J. , Salhab Mohamed , Chavez Julio C. , Reddy Nishitha M. , Karmali Reem , Umyarova Elvira , Bachanova Veronika , Glenn Martha Jane , Xavier Ana Carolina , Zhou Zheng , Hernandez-Ilizaliturri Francisco J. , Barta Stefan K. , Lansigan Frederick , Mehta Amitkumar N. , Flowers Christopher , Cohen Jonathon Brett , Fenske Timothy S , Hamadani Mehdi , Costa Luciano J 
Published: September 2018

7541 Background: Translocations involving MYC are a hallmark of poor prognosis among patients with newly diagnosed DLBCL. The impact of MYC translocations with or without additional “hits” involving BCL2 or BCL6 in response to salvage therapy and survival in R/R DLCBL is not well defined. Methods: We performed a multicenter retrospective study of 176 patients with R/R DLBCL failing to achieve CR or relapsing within 6 months after completion of upfront chemoimmunotherapy and for whom FISH information on MYC, BCL2 and BCL6 was available. The objectives were to examine the response to salvage therapy, utilization of hematopoietic cell transplantation (HCT) and survival outcomes in MYC- (n = 120), MYC+ single hit (SH, n = 28), and MYC+ double hit (DH, n = 36) R/R DLBCL. Results: Overall response rate to first salvage therapy and utilization of HCT was comparable between the 3 cohorts (Table). 2-year OS was 0% in MYC+ SH, 8.8% in MYC+ DH and 29.9% in MYC- cases (p = 0.001) without difference in OS between SH and DH (P = 0.8). The higher risk of death for MYC+ SH (HR 1.79, 95% C.I. 1.03-3.11, P = 0.03) and MYC+ DH (HR 1.93, 95% C.I. 1.23-3.00, P = 0.004) persisted after adjustment for covariates. For patients who underwent auto-HCT, 2-year OS was 0% in MYC+ SH, 29.3% in MYC+ DH and 55.4% in MYC- cases (p < 0.001) without significant difference between SH and DH (P = 0.8). All 4 MYC+patients who underwent allo-HCT relapsed in < 4 months. Conclusions: MYC+ R/R DLBCL have similar response to salvage therapy than the MYC- counterparts but dismal survival irrespective of additional “hits” and even if HCT can be performed. MYC+ R/R DLBCL represents an unmet medical need and should be prioritized for clinical trials with novel agents and innovative cellular therapies. [Table: see text]
Treatment patterns among elderly follicular lymphoma patients diagnosed between 2000 and 2011: An analysis of linked SEER-Medicare data.
Authors: Onukwugha Ebere , Nagarajan Madhu , Albarmawi Husam , Gardner James F. , Keating Karen N. , Valderrama Adriana , Malacan Jean , Yaldo Avin , Yared Jean 
Published: September 2018

7563 Background: There are multiple treatment regimens approved for the management of follicular lymphoma (FL). However, there is limited information available to describe the course of therapy (COT) that patients receive following FL diagnosis. Methods: Using the linked Surveillance, Epidemiology, and End Results (SEER) registry & Medicare claims dataset, we analyzed patients 66 years and older diagnosed with FL from 2000 to 2011. In order to characterize FL treatments, we identified first, second and subsequent-lines of therapy listed in the National Comprehensive Cancer Network guidelines 2.2016. We identified the first COT (COT1) as the first regimen that a patient receives after diagnosis. We identified the second and third COT (COT2 and COT3) as new treatment received following/interrupting COT1 or COT2, respectively. Using visual analytics software, we investigated and reported the proportion of patients receiving each COT, the top three regimens within each COT, and the median time to starting a COT from diagnosis or end of a previous COT. Results: 10,836 FL patients were identified after applying the inclusion/exclusion criteria. Sixty-two percent (N=6,756) of the patients received FL-directed treatment. Among patients receiving COT1, 65% received COT2. Among patients receiving COT2, 79% received COT3. The table below provides additional information on the COT received. Conclusions: Analysis of real-world data indicates that almost 4 out of 10 elderly FL patients do not receive the listed FL-directed treatments. In contrast to rituximab, there was limited use of RCHOP and RCVP after COT1 during the study period. Additional research is needed to understand the differences across demographic groups and associated health outcomes. [Table: see text]
Efficacy of daratumumab in combination with lenalidomide plus dexamethasone (DRd) or bortezomib plus dexamethasone (DVd) in relapsed or refractory multiple myeloma (RRMM) based on cytogenetic risk status.
Authors: Weisel Katja C. , San Miguel Jesus , Cook Gordon , Leiba Merav , Suzuki Kenshi , Kumar Shaji , Cavo Michele , Avet-Loiseau Herve , Quach Hang , Hungria Vania , Lentzsch Suzanne , Hajek Roman , Sonneveld Pieter , Wu Kaida , Qin Xiang , Chiu Christopher , Soong David , Qi Ming , Schecter Jordan Mark , Dimopoulos Meletios A. 
Published: September 2018

8006 Background: In 2 randomized phase 3 trials of RRMM patients (pts), DRd (POLLUX) or DVd (CASTOR) significantly improved PFS and deepened responses compared with Rd or Vd alone, respectively. The novel mechanism of action of daratumumab (D) may improve the poor prognosis associated with high-risk cytogenetic abnormalities in RRMM. Therefore, we examined the efficacy of DRd and DVd among RRMM pts with standard (std) or high cytogenetic risk status. Methods: Bone marrow aspirates were collected at screening and assessed centrally via next generation sequencing (NGS). Pts with high-risk cytogenetics included those who had ≥1 of the following abnormalities: t(4;14), t(14;16), or del17p; std-risk pts were defined as those confirmed negative for these abnormalities. Efficacy analyses included PFS and ORR. Results: Samples from 311/569 pts in POLLUX and 353/498 pts in CASTOR were assessed via NGS. In POLLUX, the median duration of follow-up was 17.3 months. Significantly longer median PFS and numerically higher ORR were observed with DRd vs Rd among high-risk patients, and significant improvements in these outcomes were observed in std-risk patients (Table). In CASTOR, the median duration of follow-up was 13.0 months. Significantly longer median PFS and higher ORR were observed with DVd vs Vd among both high- and std-risk pts (Table). Concordance rates for t(4;14), t(14;16), and del17p were high (88%-98%) between NGS and FISH. Updated data, including subgroup analyses, will be presented. Conclusions: In RRMM pts, the addition of D to standard-of-care regimens improved outcomes regardless of cytogenetic risk status. Targeting CD38 by combining D with Rd or Vd appears to improve the poor outcomes associated with high-risk cytogenetic status. See table. Clinical trial information: NCT02136134 and NCT02076009. [Table: see text]