bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preventing hepatitis B reactivation in HBsAg-positive patients with untreated diffuse large B-cell lymphoma with R-CHOP chemotherapy: A prospective study to compare entecavir and lamivudine.
Authors: Huang He , Li Xue Ying , Li Hao Ran , Shrestha Dr.Prem Raj , Guo Cheng-cheng , Liang Chao Yong , Liu Tingzhi , Zhang Mengping , Hong Huang Ming , Lin Jia Tian , Huang Jia Jia , Tian Ying , Lin Tongyu 
Published: March 2020

8503 Background: Hepatitis B reactivation is a serious complication in lymphoma patients treated with rituximab-contained chemotherapy despite lamivudine prophylaxis. The optimal prophylactic antiviral protocol is undetermined. This prospective study was designed to compare the efficacy of prophylactic entecavir and lamivudine in preventing hepatitis B reactivation in HbsAg-positive patients with untreated diffuse large B cell lymphoma (DLBCL) under R-CHOP treatment. Methods: HBsAg carriers with untreated DLBCL, normal liver function and low serum HBV DNA levels (less than 103copys/ml)were randomized to receive entecavir or lamivudine during R-CHOP treatment and for 6 months after completion of chemotherapy. HBsAg, HBsAb, HBeAg, HBeAb and HBcAb were performed prior to initiation of treatment. Serum alanine aminotransferase (ALT), and HBV-DNA levels were prospectively monitored before every cycle of chemo and every month after completion of chemotherapy. Results: Between February 2008 and December 2012, a total of 229 patients older than 18y with newly diagnosed DLBCL were included. The present analysis is based on 121 HBsAg-positive patients, including 61 patients randomly assigned to entecavir and 60 patients to lamivudine .The primary efficacy end point was the incidence of HBV-related hepatitis. The secondary end point was chemotherapy disruption due to hepatitis. Compared with the lamivadine group, the entecavir group had significantly lower rates of hepatitis(8.2% vs 23.3%,P=0.022), hepatitis B reactivation (0 vs 13.3%,P=0.003),HBV reactiviation(6.6% vs 30.0%,P=0.001), delayed HBV-related hepatitis (0 vs 8.3%,P=0.027) and disruption of chemotherapy (1.6% vs 18.3%,P=0.002). 7 of 8 patients with hepatitis B reactivation had advanced stage(III–IV) disease. Conclusions: In HBsAg-positive DLBCL patients undergoing R-CHOP chemotherapy, entecavir is more effective than lamivudine in preventing hepatitis B reactivation. For patients with advanced stage disease, entecavir should be considered the primary preventive therapy. Clinical trial information: CTR-TRC-11001687.
Melphalan/prednisone/lenalidomide (MPR) versus high-dose melphalan and autologous transplantation (MEL200) plus lenalidomide maintenance or no maintenance in newly diagnosed multiple myeloma (MM) patients.
Authors: Boccadoro Mario , Cavallo Federica , Gay Francesca Maria , Di Raimondo Francesco , Nagler Arnon , Montefusco Vittorio , Patriarca Francesca , Tacchetti Paola , Guglielmelli Tommasina , Musto Pellegrino , Baldini Luca , Crippa Claudia , Ruggeri Marina , Gentilini Fabiana , Cavalli Maide , Ben Yehuda Dina , Caravita Tommaso , Ciccone Giovannino , Hardan Izhar , Palumbo Antonio 
Published: March 2020

8509 Background: The incorporation of new drugs into induction, consolidation, and maintenance therapy is changing the treatment paradigm of MM. Methods: At diagnosis, 402 pts (< 65 years) were randomly assigned to receive six MPR cycles (N=202) or tandem MEL200 (N=200). After MPR or MEL200, pts were further randomized, within each group, for no maintenance (N=204) or lenalidomide maintenance (N=198). A 2x2 factorial randomized trial was designed. The primary end point was PFS. An enrolment of 170 pts/arm was required to demonstrate a 15% improvement of PFS at 2 years (2-sides a = 0.05, 1- β 80%). Results: After a median follow-up of 45 mos from diagnosis, the median PFS was 25 mos with MPR and 39 mos with MEL200 (p=.0002). Median PFS were 37.5 mos for maintenance and 25.7 mos for no maintenance (p=.0008). The 4-year OS from diagnosis was 71% with MPR and 72% with MEL200 (p=0.71), 76% for maintenance and 68% for no maintenance (p=.08). After a median follow-up of 32 mos from start of maintenance, the median PFS was for 41 mos for maintenance and 18 mos for no maintenance (p<.0001). The 3-year OS from start of maintenance was 81% for maintenance and 72% for no maintenance (p=.04). Conclusions: MEL200 significantly prolonged PFS in comparison with MPR. Lenalidomide maintenance significantly reduced the risk of progression independently from the previous treatment. OS is similar between MPR and MEL200, with a trend for an improved OS in pts receiving lenalidomide as maintenance therapy. Clinical trial information: NCT00551928. [Table: see text]
Prognostic value of deep sequencing method for minimal residual disease (MRD) detection in multiple myeloma.
Authors: Martinez-Lopez Joaquin , Garcia-Sanz Ramon , Pepin Francois , Ayala Rosa , Montalban Maria Angeles , Paiva Bruno , Weng Li , Barrio Santiago , Montejano Laura , Rapado Immaculada , Martinez Rafael , Blachard Maria Jesus , Sanchez-Godoy Pedro , Blade Joan , San-Miguel Jesùs F. , Faham Malek , Lahuerta Juan José 
Published: March 2020

8511 Background: Most multiple myeloma (MM) patients will relapse due to persistence of residual tumor cells, or MRD. We compared the prognostic value of traditional response criteria and MRD measurement by a sequencing-based method, LymphoSIGHT, and multiparameter flow cytometry (MFC) in a cohort of 68 uniformly-treated MM patients from the Spanish Myeloma Group trials. Methods: Bone marrow samples were obtained from 68 patients at diagnostic and post-treatment time points on GEM clinical trials (GEM00 and GEM05). All patients were in CR or VGPR at the post-treatment time point. Using sequencing, we identified clonal rearrangements of immunoglobulin (IGH-VDJ, IGH-DJ, and IGK) genes in diagnostic samples. We assessed MRD in follow-up samples, analyzed concordance between sequencing and MFC MRD results, and compared the prognostic value of each method with traditional response criteria. Results: The sequencing assay detected a myeloma-specific gene rearrangement in diagnostic samples from 59 of 68 (87%) patients. We tested MRD in follow-up time points in 56 of the 59 patients. We observed high correlation between MFC and sequencing MRD results (r2=0.86), with MFC underestimating the myeloma burden (Slope=0.4). Of the 56 patients, 45 were positive by sequencing at MRD levels of 10-5 or higher and 11 were MRD negative. There was significantly improved overall survival (OS) in the MRD negative group versus the MRD positive group (median not reached vs. 86 mos, p=0.026). Similar differences were found in progression free survival. When limiting the analysis to the 35 patients in conventional CR, 24 of 35 patients were positive by sequencing at MRD levels at 10-5 and higher and 10 were MRD negative. There was significantly improved OS in the MRD negative group versus the MRD positive group (median not reached vs. 80.92 mos, p=0.041). Conclusions: Our data shows high correlation between MFC and sequencing MRD levels in MM patients. For patients in CR by traditional response criteria, the presence or absence of MRD by sequencing delineated 2 groups of patients with significantly different OS. MRD negativity by sequencing may be a better prognostic indicator than CR by traditional response criteria.
Final results of a phase I study of idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase P110δ (PI3Kδ), in patients with relapsed or refractory mantle cell lymphoma (MCL).
Authors: Spurgeon Stephen Edward Forbes , Wagner-Johnston Nina D. , Furman Richard R. , Flinn Ian , Coutre Steven E. , Brown Jennifer R. , Benson Don M. , Byrd John C. , Leonard John , Peterman Sissy , Johnson David Michael , Gu Jessie , Dansey Roger D. , Godfrey Wayne R. , Kahl Brad S. 
Published: March 2020

8519 Background: PI3K-delta signaling is critical for activation, proliferation and survival of B cells and plays a role in homing and retention in lymphoid tissues. PI3Kδ signaling is hyperactive in many B-cell malignancies. Idelalisib is a first-in-class, selective, oral inhibitor of PI3Kδ. Initial response rate of 42% was previously reported in MCL (Kahl, ICML 2011). Long-term follow-up is now presented. Methods: This phase 1 study evaluated the activity of continuous (48 weeks) idelalisib monotherapy in pts with relapsed or refractory hematologic malignancies. Doses ranged from 50 mg BID to 350 mg BID in 8 cohorts. Response was based on investigator assessments using standard criteria (Cheson et al, 2007). Patients who continued to benefit were able to enroll in an extension study. Results: 40 patients with recurrent MCL enrolled. Patients were 88% male, median age [range] of 69 [52-83] years, 43% with refractory disease. The median [range] number of prior therapies was 4 [1E14]. The median [range] duration of idelalisib treatment was 3.5 [1-26+] months, with 6 (15%) patients continuing on treatment in the extension protocol. Overall response rate (ORR) was 16/40 (40%), with 2/40 CR (5%). The median duration of response (mDOR) was 2.7 months, and median PFS (mPFS) was 3.7 months. The 1-year PFS was 22%. For patients dosed with ≥100 mg BID, ORR was 12/23 (52%), for patients dosed with ≥150 mg BID, ORR was 11/16 (69%) including both CR (12.5%). Most common adverse events included (total%/≥G3%); diarrhea (40/18), nausea (33/5), pyrexia (28/0), fatigue (25/3), rash (25/3), decreased appetite (20/15), URI (20/0), and pneumonia (13/13). Abnormal lab values included (total%/≥G3%) ALT/AST elevations (65/20). 6/40 (15%) patients discontinued therapy due to AEs, potentially treatment related. Conclusions: The oral PI3Kδ inhibitor idelalisib (GSE1101) is active and well tolerated in heavily pre-treated pts with MCL. A proportion of patients have long-term (>1 year) clinical benefit. These data support further clinical evaluation of idelalisib in MCL. Clinical trials with idelalisib in combination with other agents are in progress. Clinical trial information: NCT00710528.
Final results of a phase I study of idelalisib, a selective inhibitor of PI3Kδ, in patients with relapsed or refractory indolent non-Hodgkin lymphoma (iNHL).
Authors: Benson Don M. , Kahl Brad S. , Furman Richard R. , Brown Jennifer R. , Wagner-Johnston Nina D. , Coutre Steven E. , Spurgeon Stephen Edward Forbes , Byrd John C. , Leonard John , Peterman Sissy , Johnson David Michael , Cho Yoonjin , Dansey Roger D. , Godfrey Wayne R. , Flinn Ian 
Published: March 2020

8526 Background: PI3K-delta signaling is critical for activation, proliferation and survival of B cells, plays a role in homing and retention in lymphoid tissues, and is hyperactive in many B-cell malignancies. Idelalisib (GS-1101) is a first-in-class, selective, oral inhibitor of PI3Kδ. Initial response rate of 38% was reported previously in iNHL (Kahl, ICML 2011). Long-term follow-up is now presented. Methods: This phase 1 study evaluated the activity of continuous idelalisib monotherapy in pts with relapsed hematologic malignancies. Doses ranged from 50 to 350 mg QD or BID in 8 cohorts. Response was evaluated based on investigator assessments using standard criteria (Cheson, 2007). Pts who continued to benefit were able to enroll in an ongoing extension study. Results: Study enrolled 64 pts with indolent iNHL. iNHL subtypes included 38 FL, 11 SLL, 9 LPL/WM, and 6 MZL. Pts were 69% male, median age [range] of 64 [32E91] years, 58% with refractory disease and 53% with bulky disease (LN diameter ≥5 cm). The median [range] number of prior therapies was 4 [1E10]. The median [range] duration of treatment was 3.8 [0-41] months, with 19 (30%) pts continuing on treatment extension protocol. ORR across all cohorts were 31/64 (48%), with 1 CR (1.6%). The median duration of response (mDOR) was 18.4 months, and median PFS (mPFS) was 7.6 months. For pts dosed with ≥100 mg BID (N=36); the ORR was 24/36 (67%), the mDOR was 15.4 months, and the mPFS was 16.6 months. The ORR for iNHL subtypes was: FL (45%), SLL (64%), LPL/WM (56%), and MZL (33%). Adverse events included (total%/≥G3%) diarrhea (36/8), fatigue (36/3), rash (27/3), nausea (25/2), pyrexia (20/3), chills (20/0), cough (19/2), pneumonia (17/16), and URI (17/0). Lab abnormalities included (total%/≥G3%) ALT/AST elevations (56/25). 8/64 (12.5%) pts discontinued therapy due to potentially treatment-related adverse events. Conclusions: The oral PI3Kδ inhibitor idelalisib is active in heavily pretreated pts with iNHL, can produce durable responses, and has a favorable safety profile. These data support further clinical development; phase 2 and 3 trials in iNHL are ongoing (NCT01732913, NCT01732926). Clinical trial information: NCT00710528.
Pomalidomide plus low-dose dexamethasone (POM + LoDEX) versus high-dose dexamethasone (HiDEX) in relapsed/refractory multiple myeloma (RRMM): MM-003 analysis of patients (pts) with moderate renal impairment (RI).
Authors: Weisel Katja C. , Dimopoulos Meletios A. , Moreau Philippe , Lacy Martha , Song Kevin W. , Delforge Michel , Karlin Lionel , Goldschmidt Hartmut , Banos Anne , Rocafiguera Albert Oriol , Yu Xin , Sternas Lars , Jacques Christian , Zaki Mohamed H. , San-Miguel Jesùs F. 
Published: March 2020

8527 Background: Pts who have exhausted lenalidomide (LEN) and bortezomib (BORT) treatment (Tx) have a poor prognosis. A significant proportion of pts have RI with increasing incidence during disease course. POM + LoDEX has demonstrated efficacy in pts with prior LEN and BORT, including those with RI. MM-003 is an open-label, multicenter, phase 3 trial comparing POM + LoDEX vs HiDEX in RRMM pts who failed LEN and BORT and progressed on their last Tx. Methods: Pts must have failed LEN and BORT after ≥ 2 consecutive cycles of each (alone or in combination) and must have been refractory to last prior Tx (progressive disease [PD] during Tx or within 60 days). Pts with creatinine clearance (CrCl) < 45 mL/min were excluded. Randomization was 2:1 to POM 4 mg D1–21 + DEX 40 mg (20 mg for pts aged > 75 y) qw; or DEX 40 mg (20 mg for pts aged > 75 y) D1–4, 9–12, and 17–20 (28-D cycles). Tx continued until PD or unacceptable adverse event (AE). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and AEs. This analysis examined pts with or without moderate RI (CrCl < 60 vs ≥ 60mL/min). Results: 302 pts received POM + LoDEX; 153 pts received HiDEX, 31% and 39% had moderate RI, respectively. Pts with moderate RI were more likely to be older (64% vs 36% aged > 65 y) vs no RI. Median follow-up was 4 mo. Median PFS and OS were significantly longer with POM + LoDEX vs HiDEX regardless of RI (Table). Similar AE rates for POM + LoDEX as well as HiDEX Tx were seen in pts with and without moderate RI (Table). Discontinuation due to AE was 5% vs 7% (no moderate RI) and 11% vs 5% (moderate RI). Conclusions: POM + LoDEX significantly extended PFS and OS vs HiDEX in pts with or without moderate RI. Tolerability of POM + LoDEX was acceptable across subgroups, with few discontinuations due to AE. Clinical trial information: NCT01311687. [Table: see text]
Final results from the phase Ib/II study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone (CRd) in patients with relapsed or progressive multiple myeloma.
Authors: Wang Michael , Martin Thomas , Bensinger William , Alsina Melissa , Siegel David Samuel DiCapua , Kavalerchik Edward , Niesvizky Ruben 
Published: March 2020

8529 Background: Carfilzomib (CFZ) is approved in the US as single-agent treatment for patients with multiple myeloma (MM) who have progressed after bortezomib (BTZ) and an IMiD and are refractory to last line of treatment. We previously reported interim data from PX-171-006 (NCT00603447), a Ph 1b/2 study of CRd in relapsed or progressive MM (Wang et al. ASCO 2011). Herein we report final results. Methods: Patients (1–3 prior treatments) received CRd in 28-day (D) cycles—CFZ IV on D1, 2, 8, 9, 15, 16, lenalidomide (LEN) PO D1–21, and dexamethasone (dex) wkly. In phase 1, CFZ (15–27 mg/m2) and LEN (10–25 mg) doses were escalated to determine the maximum tolerated dose (MTD) with a maximum planned dose (MPD) of CFZ 20 mg/m2 D1, 2 of Cycle 1 and 27 mg/m2 thereafter, LEN 25 mg/d, and dex 40 mg/wk, followed by phase 2 expansion at MTD/MPD. Endpoints included IMWG overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and safety. Results: A total of 84 patients were enrolled since June 2008. Overall, prior treatment included BTZ (77%/18% refractory) and LEN (70%/35% refractory); 20% had high-risk cytogenetics/FISH. MTD was not reached in Ph 1, supporting expansion at the MPD (n=52, 23% BTZ refractory and 42% LEN refractory). As of Nov 2012 (median follow-up 24.4 mo): ORR was 69% overall and 76.9% at MPD with very good partial response in 36.9% and 38.5% and stringent complete response in 3.6% and 3.8%, respectively; median DOR was 18.8 (95% CI 9.7–41.5) and 22.1 mo (95% CI 9.5–NE) respectively; median PFS was 11.8 (95% CI 7.6–20.7) and 15.4 mo (95% CI 7.9–NE), respectively. Seven responders at MPD pursued other therapy and were censored for PFS.A median of 8.5 (range 1−46) CFZ cycles were started; 4% required CFZ dose reductions; 15% discontinued CFZ due to adverse events (AEs). Grade 3/4 AEs were generally consistent with earlier studies in advanced MM that used similar doses of single-agent CFZ; grade 3/4 peripheral neuropathy was 1%. Conclusions: CRd was well tolerated, providing robust and durable responses in this pt population where 35% were LEN refractory. This combination is being further evaluated in several ongoing phase 2/3 trials. Clinical trial information: NCT00603447.
Changes in the tumor microenvironment associated with transformation in follicular lymphoma.
Authors: Smeltzer Jacob Paul , Jones Jason Michael , Ziesmer Steven , Grote Deanna , Yang Zhi Zhang , Novak Anne , Xiu Bing , Ristow Kay , Ansell Stephen Maxted 
Published: March 2020

8538 Background: Follicular lymphoma (FL) is a heterogeneous disease with a variable prognosis. Transformation to an aggressive lymphoma is associated with a poor prognosis. Previous studies have identified tumor microenvironment cells such as CD68+ macrophages, PD-1+ and FOXP3+ cells as prognostic in FL. However, results have been conflicting and infrequently address the risk of transformation. In this study we analyzed various components of the microenvironment and their association with transformation. Methods: Patients with FL that later transformed were identified through Mayo Clinic lymphoma database. Tissue specimens at diagnosis were stained with CD68, CD11c, CD21, CXCL13, FOXP3, PD-1 and CD14 and characterized by pattern of location and semi-quantitative cell content. Time to transformation (TTT) and overall survival (OS) were assessed by Kaplan-Meir analysis. Significant variables were further analyzed by cox proportional hazards model. Results: 58 patients were included with a median TTT of 4.7 years (range, 0.4-20). Presence of CD14+ cells vs absence and their location (follicular vs non-follicular) were associated with shorter TTT (4.5 vs 6.2 yrs., p=0.037 and 3.8 vs 5.9 yrs. p= 0.027, respectively). The quantity of PD-1+ cell content was not associated with TTT or OS. However, localization of PD-1 to the follicle compared to diffuse was associated with a longer TTT (6.1 vs 3.6 yrs. p=0.033) and superior OS (9.7 vs 4.6 yrs. p=0.009). On multivariate analysis, the pattern of CD14 and PD-1 staining remained significantly associated with shorter TTT (Table). Conclusions: In follicular lymphoma, a diffuse pattern of PD-1+ cells is associated with inferior TTT and OS. CD14+ cells localized to the follicle is associated with a shorter TTT. After accounting for FLIPI score, both these factors remained significant. These results identify two independent predictors of the rate of transformation in follicular lymphoma and suggest it is location rather than quantity of CD14+ or PD-1+ cells that influence outcomes. [Table: see text]
Total therapy 5 (TT5) for newly diagnosed high-risk multiple myeloma (HRMM): Comparison with predecessor trials total therapy 3a and 3b (TT3 a/b).
Authors: Usmani Saad Zafar , Waheed Sarah , Van Rhee Frits , Mitchell Alan , Restrepo Alejandro , Grazziutti Monica , Crowley John , Barlogie Bart 
Published: March 2020

8539 Background: HRMM has not benefited from advances achieved in the remainder 85% with low-risk MM. In order to guard against relapses during previous drug-free intervals in TT3, TT5 was designed as a dose-dense and less dose-intense program. Here we are reporting for the first time on the TT5 outcomes in comparison with TT3a/b results in HRMM. Methods: TT5 called for M-VTD-PACE induction with HPC collection. This was followed by tandem autologous stem cell transplants (ASCT) with hybrid regimens Mel80 plus VRD-PACE, sandwiched in between were 2 inter-transplant cycles of MEL20-VTD-PACE. Maintenance consisted of 3 years of alternating VRD and VMD (M, melphalan). As relapses were observed during maintenance, bortezomib was increased from 1.3mg/m2 to 1.5mg/m2 weekly. Results were compared with HRMM treated with TT3a/b (n=40/37). Data were compared with TT3 HRMM, involving 77 patients. Overall survival and progression free survival was analyzed employing Kaplan-Meier curves. Cox regression modeling was done for univariate and multivariate analyses. Results: Of 59 patients enrolled in TT5, CR was 66% including 10% with s-CR. The 18-mo OS was 92% v 74% with TT3 (p=0.009), whereas PFS was similar at 67% and 69%, respectively. A newly developed GEP-5 model distinguished 8 patients with a 36-mo OS estimate of 20% versus almost 90% for the remainder (p=0.04). On multivariate analysis that included TT5 and TT3, our GEP80 low-risk score, TT5 (vs TT3) and age <65yr were independent features linked to superior OS. Conclusions: This isthe first report of a dose-dense chemotherapeutic approach for newly diagnosed HRMM, which also introduced a hybrid Mel80-VRDPACE hybrid preparative regimen for ASCT. TT5 represents an advance in the management of GEP70-defined HRMM compared to predecessor trials TT3a/b for similar patients, with significant improvement in overall survival and tolerability compared with TT3 a/b. Clinical trial information: NCT00081939, NCT00572169, NCT00869232.
The LIMD1-MYBL1 index as a composite marker for subtype classification and survival prediction for diffuse large B-cell lymphoma patients.
Authors: Xu Qinghua , Tan Cong , Ni Shujuan , Yuan Lin , Wu Fei , Liu Fang , Ye Xun , Meng Xia , Sheng Weiqi , Du Xiang 
Published: March 2020

8547 Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of B-cell lymphomas with wide variations in patient survival. Through gene expression profiling, DLBCL can be stratified into two major cell-of-origin subtypes with distinct prognoses: the favorable germinal center B-cell-like (GCB) and the unfavorable activated B-cell-like (ABC) DLBCLs. However, the current cell-of-origin signatures are not suitable for use in routine clinical practice. Our study aimed to identify a novel biomarker to facilitate the translation of research into clinical practice. Methods: We performed an integrative analysis of seven independent cohorts comprising 1,682 patients. The DLBCL-1 cohort was used for signature identification. The identified signature was then tested in the DLBCL-2 to DLBCL-7 cohorts. Results: Two genes (LIMD1 and MYBL1) were significantly differentially expressed between the ABC and GCB subtypes. We integrated these genes into a composite marker, the LIMD1-MYBL1 Index. In seven independent cohorts, the average concordance rate between the LIMD1-MYBL1 Index and the cell-of-origin signature classification was 87% (range, 77% to 94%). Furthermore, the LIMD1-MYBL1 index is an independent prognostic factor for patients from different populations and for patients treated with a variety of therapies (Table). Conclusions: We identified the LIMD1-MYBL1 Index that has clinical value for DLBCL subtype classification and prognosis. Although little is known about the oncogenic roles of these genes, our findings prompt further research on the molecular mechanisms of DLBCL. [Table: see text]