bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathologic characteristics and outcomes of transformed diffuse large B-cell lymphoma in hepatitis C virus-infected patients: A case-control study of 84 patients.
Authors: Hosry Jeff , Miranda Roberto N. , Turturro Francesco , Economides Minas P. , Samaniego Felipe , Torres Harrys A. 
Published: September 2018

7553 Background: Chronic hepatitis C virus (HCV) infection is associated with development of marginal zone lymphoma (MZL) and diffuse large B-cell lymphoma (DLBCL). Preliminary data showed particular characteristics of HCV-associated DLBCL; such as frequent transformation from indolent lymphomas and aggressive oncologic courses. We studied herein the clinicopathologic characteristics and outcomes of HCV-infected patients (pts) with transformed DLBCL. Methods: In this case control study, the medical records and pathology reports of HCV-infected (cases) and HCV-uninfected (controls) pts with transformed DLBCL seen at our institution (6/2004 - 5/2015) were reviewed. Included pts had a concomitant or a history of a low grade lymphoma. To determine their clinicopathologic characteristics, cases were compared to controls at a ratio of 1:3. To determine predictors of oncologic relapse, we compared pts with DLBCL relapse after first line chemotherapy to those who did not relapse in univariate and logistic regression analyses. Results: Twenty-one cases were compared to 63 controls. Compared to controls, cases were younger (median year age [interquartile range], 54 [49-62] v 62 [53-66], P = .01), had advanced Ann Arbor stages, 3-4 (95% v 76%, P = .05), and upper gastro-intestinal involvement (48% v 25%, P = .05). Immunophenotypically, cases had more CD10-negative B-cells (76% v 43%, P = .008) and CD5-positive B-cells (39% v 7%, P = .004) compared to controls, consistent with an activated B-cell phenotype. A comparison between pts who relapsed after first line chemotherapy (n = 42) and those who did not (n = 40) revealed that having CD5-positive B-cells was the only factor associated with DLBCL relapse in univariate (24% v 6%, P = .03) and multivariate analyses (OR = 10.7, P= .02). Conclusions: HCV-infected pts with transformed DLBCL are younger, present with advanced stages, are more commonly CD5-positive, and have an activated B-cell phenotype, suggesting more frequent transformation from MZL compared to HCV-uninfected pts. The higher frequency of CD5-positive B-cells might explain the higher DLBCL relapses previously described in HCV-infected pts.
A single institutional experience of 261 patients with large granular lymphocytic leukemia (LGLL).
Authors: Van den Bergh Magali , Isenalumhe Leidy Lismeri , Wang Emilie , Schaible Braydon , Ma Zhenjun , Zhang Ling , Sokol Lubomir 
Published: September 2018

7555 Background: LGLL is a rare clonal lymphoproliferative disorder of post-thymic T-cell or natural killer (NK)-cell lineage associated with cytopenias, splenomegaly, autoimmune disorders, and recurrent mucocutaneous infections. Treatment is dictated by the presence of these manifestations and consists of immunosuppressive therapy. Methods: This is a retrospective analysis of clinical and laboratory features, treatment modalities, and outcomes of LGLL patients evaluated at Moffitt Cancer Center between 1995 and 2016. Continuous and categorical variables were tested via Kruskal-Wallis ANOVA and Fisher’s Exact Test. Kaplan-Meier curves were used for overall survival (OS). P-values were two-sided with significance set at < 0.05. Results: We identified 261 patients with LGLL (91.6% T, 8.4% NK). Median age was 66 years [21-90] and M:F ratio 1.2:1. Median follow up was 3.07 years [0-21.88]. 42.9% presented with anemia, 37.1% neutropenia, 30.7% thrombocytopenia, 29.1% bicytopenia and 6.9% pancytopenia. Transfusion dependence was noted in 20.3%, splenomegaly in 27.2% and bone marrow (BM) involvement in 69.3%. 24.9% had autoimmune diseases and 9.2% autoimmune cytopenias. 45.6% were observed while the remainder required at least 1 line of therapy. 5-yr and 10-yr OS were 75.0% and 63.1% respectively. There was no statistically significant difference in OS, complete response or duration of response based on first line agent (methotrexate, cyclophosphamide, cyclosporine A). However, there was a statistically significant improved partial response with methotrexate versus other therapies (p=0.01). A marginally significant association between severe anemia/transfusion dependence and poor overall response rate (p=0.075) to any therapy was noted. There was no statistically significant difference in OS based on absolute LGL count. Mean number of therapies was 1.08 (range 0-6) and was higher in those with LGL count <0.5 k/μL (p=0.0078), BM involvement (p<0.0001), and splenomegaly (p<0.0001). Conclusions: In this large retrospective study, we described the frequency of LGLL-associated manifestations and their impact on the course of LGLL. We confirmed that there is no difference in OS among first line therapies.
Results of GROC-rev salvage regimen: Gemcitabine, rituximab, and oxaliplatin chemotherapy with revlimid for relapsed/refractory aggressive non-Hodgkin lymphoma (NHL).
Authors: Cabanillas Fernando , Liboy Idalia , Cruz Alexis , Solivan Pedro Gil , Rivera Noridza , Pardo Wandaly Ibis , Acosta Mirelis 
Published: September 2018

7556 Background: Currently there is no optimal salvage regimen for relapsed/refractory NHL (R/R NHL). Prognosis of pts who fail to achieve CR to salvage therapy is dismal. We sought to improve the CR rate by adding Lenalidomide (L) to GROC (ASCO #8530, 2008). Methods: Primary endpoint was rate of conversion to CR after switch to L for pts whose best response to GROC was <CR. Secondary endpoint was progression free survival (PFS) of all pts as well as those who achieve <CR on chemotherapy and were crossed over to L.Pts who failed to achieve at least PR after GROC x2 and those who didn’t achieve CR after GROC x6, were crossed over to L 25 mg x 3 weeks q 28 days. CRs were maintained on L x 2 yrs. Results: 34 pts were enrolled of which 32 are evaluable. Median age: 61 and 56% males. Histologies included DLBCL (81%), PTCL (9%), follicular grade 3-B (9%). Stage was III-IV in 75% and median IPI=2. Best overall response rate (ORR) at any point during treatment= 19/32 (59%) and CR 13/32 (41%). ORR before crossover to L=13/32 (41%) and CR= 8/32 (25%). There were 24 who failed to achieve CR on GROC (19 who didn’t respond at all and 5 whose maximum response was PR). Of these, 21 crossed over to L and 7 (33%) responded (CR in 5, PR in 2). The fact that 5 pts attained a CR to L thus improving the CR rate from 25% to 41% after exhibiting refractoriness to GROC is noteworthy. Of the 7 responders to L, all are alive and only 1 relapsed. At 2 yrs., overall survival (OS) was 48% and PFS 35%. This compares favorably with our previous GROC study without L in which 2 yr. OS= 33% and PFS 29%. In total, 11 pts were eligible for ASCT after chemo plus L and 8 were transplanted (3 refused). Of these eight, 6 remain in CR at 11, 18, 21, 22, 52, 74 mos. At 2 yrs, PFS for transplanted pts is 73% and for those whose response to GROC before crossover to L was <CR, it is 27 mos. Toxic events included 2 neutropenic fevers, 1 MDS (34 mos. after ASCT) and 1 AML (11 mos. after ASCT). Both of these remain continuously in CR after allo SCT. Conclusions: 2 yrOS=48% and PFS=35% with GROC-Rev are the best observed with any salvage regimen we have tested. L is active as a single agent in 29% of cases whose best response to GROC was <CR. A larger study is desirable to confirm these data. Clinical trial information: NCT01307592.
Development of a clinical trial immunohistochemistry (IHC) assay using a novel antibody to CD38.
Authors: Wakamiya Karen , Hudson Marsha , Finkelstein Hayley , Nguyen Mai , Alvarez Sara , Neill Brad , William Josette , Hanks Debra Ann , Jansson Malinka , Northrup Adam , Alvarez John David , Oroudjev Emin 
Published: September 2018

7561 Background: CD38 is a type II transmembrane glycoprotein expressed on normal lymphoid and myeloid cells and can be highly expressed in hematologic malignancies. An IHC prototype assay was developed to detect CD38 expression in formalin-fixed, paraffin-embedded (FFPE) tissue specimens from three relapsed or refractory non-Hodgkin’s lymphoma (NHL) subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and mantle cell lymphoma (MCL) for selection of patients for treatment with daratumumab in a Phase 2 clinical trial (NCT02413489). Methods: This assay is based on EnVision FLEX IHC technology using CD38, clone DAK-CD38, primary antibody that has been developed and manufactured by Agilent Technologies. The assay staining protocol was developed for Dako PT Link and Autostainer Link 48. Specificity of DAK-CD38 staining was demonstrated by Western blot analysis of cancer cell lysates, as well as IHC on both normal and cancer tissue. Assay precision and robustness were evaluated using commercially procured FFPE DLBCL, FL and MCL specimens. Results: CD38 IHC DAK-CD38 detected a broad range of CD38 expression in DLBCL, FL, and MCL specimens. FFPE specimens derived from cancer cell lines exhibited a range of IHC staining intensity and confirmed the reported expression of CD38 in the scientific literature. All precision and robustness results met acceptance criteria for both IHC intensity and percent positive cells staining. Conclusions: Our studies demonstrate that the Dako CD38 IHC DAK-CD38 assay is sensitive, specific, precise, and robust for the detection of CD38 expression in DLBCL, FL and MCL. This assay may also have the potential to be used for the detection of CD38 in additional tumor types.
Phase 1 trial evaluating MRG-106, a synthetic inhibitor of microRNA-155, in patients with cutaneous t-cell lymphoma (CTCL).
Authors: Foss Francine M. , Querfeld Christiane , Porcu Pierluigi , Kim Youn H. , Pacheco Theresa , Halwani Ahmad Sami , DeSimone Jennifer , William Basem M. , Seto Anita G , Ruckman Judy , Landry Michele L , Jackson Aimee L , Pestano Linda A , Dickinson Brent A , Sanseverino Mark , Rodman David M , Rubin Paul , Gordon Gilad Shalag , Marshall William S. 
Published: September 2018

7564 Background: MRG-106 is an oligonucleotide inhibitor of miR-155, a microRNA with a strong mechanistic link to CTCL, selected based on its activity in mycosis fungoides (MF) cell lines. The objective of this first-in-human study is to evaluate the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics (PK), and preliminary efficacy of MRG-106 in MF patients. Methods: This Phase 1 trial employs a dose-escalation design to evaluate either intratumoral (IT, 75 mg/dose) or subcutaneous (SC, ≤ 900 mg/dose) administration of MRG-106. Patients were required to have biopsy-proven stage I-III MF and plaque- or tumor-stage lesions. Results: Fifteen patients (12M/3F, median age 59 years) have been dosed over 1-4 weeks. All patients tolerated the IT or SC administrations well with only minor local injection reactions in 8 patients. Thirteen of 15 patients completed dosing as scheduled. There were no clinically significant MRG-106 related adverse events with the exception of one grade 3 pruritus. The MTD has not yet been reached. In the IT cohort, a reduction of ≥50% in the baseline Composite Assessment of Index Lesion Severity (CAILS) score was observed in the MRG-106 treated lesions in all 4 evaluable patients who completed dosing; such responses were maintained to the End of Study visit (Day 28 or 35). Histological examination of pre- and post-treatment biopsies of the MRG-106-injected lesion from most patients revealed a trend in reduction in neoplastic cell density and depth; 1 patient had a complete loss of the neoplastic infiltrate. Gene expression analysis of the pre- and post-treatment biopsies showed reduction of the PI3K/AKT, JAK/STAT, and NFkB survival pathways and increased cell death consistent with the expected MRG-106 mechanism of action. In the SC cohorts, 3/8 patients had a maximal decrease in their modified Severity-Weighted Assessment Tool (mSWAT) of > 39% indicative of a significant response. One patient at the 900 mg SC dose level had a possible flare of their disease after 3 doses that resolved after 3 weeks. Conclusions: Based on favorable clinical safety, efficacy and PK data, additional patients are being accrued. Updated results will be presented as available. Clinical trial information: NCT02580552.
Results of a phase II trial of efficacy and safety of entospletinib (ENTO) in patients with lymphoplasmacytoid lymphoma/Waldenstrom's macroglubulinemia (LPL/WM).
Authors: Assouline Sarit E. , Kolibaba Kathryn S. , Klein Leonard M. , Coleman Morton , Smith Mitchell Reed , Abella-Dominicis Esteban , Ye Wei , Shi Wen , Andorsky David Jacob , Sharman Jeff Porter 
Published: September 2018

7565 Background: ENTO is an orally bioavailable, selective inhibitor of spleen tyrosine kinase (Syk, a mediator of B-cell receptor [BCR] signaling). Targeting the BCR-signaling pathway has been a focus in B-cell related hematological malignancies including LPL/WM. Methods: This reports the LPL cohort in a phase 2 trial that more broadly evaluated efficacy and safety of ENTO (800 mg BID) in patients with relapsed and refractory (R/R) B-cell malignancies. Tumor response was assessed at weeks 8, 16, 24, and then every 12 weeks. The primary endpoint was PFS at week 24. Results: 17 LPL patients (median age 72 years [range: 47–89], 65% male, and median of 3 prior regimens [range: 1–8]) were enrolled. Prior therapies included anti-CD20 antibodies (100%), alkylating agents (71%; bendamustine 24%), purine analogues (24%), and vinca alkaloid (41%). No patient had prior ibrutinib. Median treatment duration was 16 weeks (range: 1-84), with 3 patients continuing on treatment. The most common treatment-emergent AEs (any grade/≥grade 3, independent of causality) were fatigue (53%, 6%), constipation (47%, 0%), nausea (47%, 6%), diarrhea (29%, 6%), insomnia (29%, 0%) and lab abnormalities including neutropenia (53%, 12%), increased creatinine (53%, 0%), increased ALT (41%, 6%) and decreased WBC (41%, 6%). One death due to progressive disease (PD) was reported within 30 days from last dose. 12 (71%) patients were evaluable for tumor response. 5 patients (29%) discontinued prior to initial tumor assessment: PD (n = 2), withdrawal consent (n = 2) and AE (n = 1). ORR was 24% (90% CI: 9%, 46%), with 1 (6%) patient achieving PR, 3 with minor response (18%) and 7 (41%) maintaining stable disease. Reductions of IgM from baseline were greatest in the patient with PR. PFS rate at week 24 was 82% (95% CI: 44%, 95%). Median time to treatment failure and median time to response were 3.7m and 1.9 m respectively. Median duration of response has not been reached. Conclusions: ENTO was well tolerated and demonstrated limited activity in patients with R/R LPL. Further development of ENTO in LPL will focus on its role in combination therapies. Clinical trial information: NCT01799889.
Phase I/II dose expansion of a trial investigating bendamustine and pomalidomide with dexamethasone (BPd) in patients with relapsed/refractory multiple myeloma.
Authors: Sivaraj Dharshan , Green Michael M. , Kang Yubin , Rizzieri David , Diehl Louis F. , Beaven Anne W. , Li Zhiguo , Garrett Anderson , McIntyre Jackie , Long Gwynn Douglas , Chao Nelson Jen An , Gasparetto Cristina 
Published: September 2018

8008 Background: The combination of bendamustine, pomalidomide, and dexamethasone (BPd) displays promising activity in heavily pretreated RRMM. In the Phase I portion, MTD was 120 mg/m2bendamustine/3mg pomalidomide/40mg dexamethasone. We report our combined findings from the additional phase II expansion cohort for the first phase I/II trial of BPd in patients with RRMM (NCT01754402). Methods: All patients had to be refractory to prior lenalidomide as well as be pomalidomide naïve, and must have relapsed or have been refractory to their most recent therapy. Treatment consisted of oral pomalidomide PO QD on days 1-21, intravenous (IV) bendamustine given over 30 minutes on day 1, and dexamethasone 40mg on days 1, 8, 15, and 22 of a 28-day cycle. Bendamustine was administered at 120 mg/m2 for cycle 1, day 1. Results: A total study population of 38 patients was enrolled, with 34 evaluable for toxicity and 32 for efficacy, with 7 patients still receiving treatment. Data cut-off was January 18, 2017. The median age was 67 years, median number of prior regimens was 5, median time from diagnosis was 3.6 years, and median follow-up was 11.7 months. 82% of patients had a prior stem cell transplant, 100% had prior bortezomib, 32% had prior carfilzomib, and all were lenalidomide refractory. Cytogenetic abnormalities included 6 patients with del(17p), 4 with t(4;14), 7 with del(13), and 7 with t(11;14). Patients received a median of 4 cycles of therapy. Best response assessments in 32 evaluable patients showed 3 sCR, 3 VGPR, 17 PR, 7 SD, and 2 PD for an ORR of 72%. The median PFS and OS were 9.6 months and 21.3 months respectively for the entire cohort, with 16 of 32 still alive at follow-up. Grade ≥3 drug-related AEs included fatigue (8%), neutropenia (45%), anemia (26%), thrombocytopenia (24%), and diarrhea (8%). 71% of patients experienced grade ≥3 AEs including neutropenia, anemia, and diarrhea. Conclusions: The BPd regimen is relatively tolerable and achieves a promising overall response rate (ORR of 72%) and durable responses in a heavily pre-treated lenalidomide–refractory population with prior bortezomib exposure, and a median of 5 lines of prior therapy. Clinical trial information: NCT01754402.
Lenalidomide induction and maintenance therapy for transplant eligible myeloma patients: Results of the Myeloma XI study.
Authors: Jackson Graham H. , Davies Faith , Pawlyn Charlotte , Cairns David A. , Striha Alina , Waterhouse Anna , Jones John , Kishore Bhuvan , Garg Mamta , Williams Cathy , Karunanithi Kamaraj , Lindsay Jindriska , Jenner Matthew , Cook Gordon , Kaiser Martin , Drayson Mark , Owen Roger G. , Russell Nigel , Gregory Walter , Morgan Gareth John ,   On Behalf of the NCRI Haemato-Oncology Clinical Studies Group
Published: September 2018

8009 Background: Immunomodulatory (IMiD) agents are effective therapies for multiple myeloma (MM), with Lenalidomide (Len) having fewer side effects than Thalidomide (Thal), enabling long-term treatment. The optimum IMiD induction and maintenance regimen are unknown. We therefore compared triplet induction regimens of Len vs Thal and examined the role of maintenance Len vs observation, enabling us to explore the interaction of Len induction with Len maintenance. Methods: Myeloma XI is a multicenter, randomized controlled trial for newly diagnosed MM, with pathways for transplant eligible (TE) and non-eligible patients. For TE patients the induction question compared Len or Thal plus cyclophosphamide and dexamethasone (CRD vs CTD) continued for a minimum of 4 cycles and to max. response. For patients with a suboptimal response there was a subsequent randomization to a proteasome inhibitor containing triplet or no further therapy prior to ASCT. A maintenance randomization at 3 months post ASCT compared Len till disease progression vs observation. 2042 TE patients underwent the induction randomization (CRD 1021, CTD 1021). After a median follow up of 36.3 months, 965 PFS and 415 OS primary endpoint events had occurred. Secondary endpoints included response and toxicity. Results: In TE patients, CRD induction was associated with deeper responses than CTD: ≥VGPR CRD 60% vs CTD 53%. This was associated with a significantly improved median PFS (HR 0.85, 95%CI 0.75, 0.96, CRD 35.9 months vs CTD 32.9, p=0.0116) and 3 year OS: 82.9% vs 77.0% (HR 0.77, 95%CI 0.63, 0.93, p=0.0072). Maintenance therapy with Len was associated with a significantly longer median PFS compared to observation (HR 0.47, 95%CI 0.38, 0.60) across all subgroups including patients with high-risk disease. Exploratory analysis across the TE pathway suggested that CRD induction with Len maintenance was optimum: 60 month PFS CRD-R 50.2%, CTD-R 39.1%, CRD-obs 18.5%, CTD-obs 23.4%. Conclusions: CRD was associated with deeper responses than CTD, and with a PFS and OS benefit. The best outcomes were associated with Len induction plus Len maintenance. Our findings support continuing Len therapy through induction until disease progression. Clinical trial information: NCT01554852.
Risk stratification of smoldering multiple myeloma (SMM): Predictive value of free light chains and group-based trajectory modeling (GBTM).
Authors: Chari Ajai , Wu Vernon , Moshier Erin 
Published: September 2018

8031 Background: A serum free light chain ratio (FLCR) ≥ 100 and bone marrow plasma cell (BMPC) ≥ 60% have recently been classified as myeloma defining events to identify a group of SMM patients at high risk (ie. > 50% risk at 2 years) of organ damage. However rates of progression for FLCr range from 30% to 98%. Reasons for the discrepancy include selection/referral bias, patient heterogeneity, and lack of consideration of disease evolution. The objective of this study was to determine the predictive value of baseline FLCR > 100 and BMPC > 60% in our patient population and also to determine the significance of m spike and FLC evolution using GBTM. Methods: We retrospectively investigated the predictive value of these events, including involved–uninvolved FLC (dFLC), in 273 consecutive SMM patients seen at our institution between 2010 and 2015. GBTM uses the outcomes of groups of individuals with similar trajectories over time (vs apriori assumptions of % change) to model population trajectories. Results: In patients with FLCR ≥ 100 at diagnosis, the median time to progression was 23 mos with 2-year progression of 52%. In patients with BMPC ≥ 60% at diagnosis, median time to progression was 25 months with 2-year progression of 47%. For 111 patients available for analysis, GBTM two distinct trajectories in dFLC during the 1st year. 18% of patients fell into a high risk group experiencing a 171% increase in dFLC at 1 year vs the remaining patients only had a 16% increase. The high risk group had a median TTP of 13.7 mos versus not reached for the remaining (log-rank p = 0.0063). Similarly the 25% of patients who had a 62% increase in mean m spike within 1 year had TTP of 27 mos versus the remaining 75% who had no increase had a median TTP of 84 mos (log rank p = 0.0943). Conclusions: Our results not only confirm a more modest 52% 2 year risk of PD with an FLCR > 100 and dFLC > 100, but also suggest that a high risk dFLC trajectory evolution may help identify a SMM high risk group, with a median TTP of only 13.7 mos. Results of multivariate analysis and sensitivity/specificity comparisons of baseline as well as evolving biomarkers will be presented at the meeting.