bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival outcomes for various treatment modalities in advanced-stage grade 3 follicular lymphoma (FL3): A National Cancer Database (NCDB) study.
Authors: Giri Upama , Vick Eric , Lee Sophia SeoHyeon , Altahan Alaa , VanderWalde Noam Avraham , Dickson Paxton Vandiver , Deneve Jeremiah Lee , Martin Michael Gary 
Published: September 2018

7554 Background: The prognosis, response to therapy and curability of FL3 is controversial. 5-year Overall Survival (OS) in the literature ranges from 35-72% (Ganti 2006). The aim of this study was to compare the OS for patients with advanced-stage FL3 managed with various treatment modalities. Methods: We identified patients (pts) diagnosed with stage III & IV FL3 between 2004 – 2012 from the NCDB and categorized them into 3 groups based on therapy – pts given single agent chemotherapy with or without radiotherapy were combined due to small sample sizes (SA±RT), multi agent chemotherapy without radiotherapy (MA-RT), and multi agent chemotherapy with radiotherapy (MA+RT). We calculated OS using Kaplan-Meier method and compared the results using Log Rank test. Cox regression model was used to identify other factors which had significant impact on OS. Results: 2,808 pts were identified – 1,508 (54%) with stage III and 1,300 (46%) with stage IV disease. Median age was 60 yrs (range 21-90yrs); 1,331 (47%) males, 1,477 (53%) females; 2,559 (91%) whites, 142 (5%) blacks. 170 cases (6%) were treated with SA±RT, 2,508 (89%) with MA-RT and 130 (5%) with MA+RT. There was no significant difference in 5-year OS between MA-RT (83%) and MA+RT (82%; HR 1.07, P=0.76). There was no difference between SA±RT (73%) and MA+RT (82%; HR 0.62, P=0.069) likely due to small sample sizes, but survival for MA-RT (83%) was significantly higher than SA±RT (73%; HR 1.78, p<0.001). Cox regression indicated that age (HR 1.04, P<0.001), sex (HR 0.77 for females, P=0.008), comorbidities (HR 1.48 for Charlson Deyo Score 1, P=0.001; HR 2.59 for Score 2, P<0.001), stage (HR 1.29, P=0.007), insurance status (HR 0.65 for insured, P=0.048) and increasing year of diagnosis (HR 0.91, P<0.001) also had significant impact on OS. Use of MA chemotherapy declined (2004 96% v 2012 91%, P=0.008) but there was no significant trend in use of radiotherapy (2004 5% v 2012 3%) during the periods studied. Conclusions: MA chemotherapy in pts with advanced-stage FL3 was associated with improved survival compared to SA therapy, and radiation does not appear to influence outcomes. Outcomes were superior to what has been previously reported.
Carfilzomib weekly-melphalan-prednisone in untreated elderly multiple myeloma: IFM2012-03.
Authors: Leleu Xavier , Fouquet Guillemette , Karlin Lionel , Kolb Brigitte , Tiab Mourad , Araujo Carla , Roussel Murielle , Bourquard Pascal , Lenain Pascal , Humbrecht-Kraut Catherine , Belhadj Karim , Petillon Marie-Odile , Chretien Marie-Lorraine , Rodon Philippe , Decaux Olivier , Jaccard Arnaud , Hulin Cyrille , Attal Michel , Moreau Philippe , Facon Thierry 
Published: September 2018

8004 Background: Melphalan-prednisone-bortezomib (MPV) is a standard of care upfront for newly diagnosed elderly myeloma (eNDMM). Despite significant improvements on MPV’s safety profile, toxicity issues remain. Carfilzomib (K) is a novel generation proteasome inhibitor with a different safety profile from Bortezomib. Carmysap phase I/II study (twice a week Carfilzomib+MP) demonstrated K at 36mg/m² safe and active in eNDMM. We thought to study the K weekly-MP combination in eNDMM. Methods: IFM2012-03 is a multicenter phase I/II study in eNDMM (65 and older) aimed to determine the maximum tolerated dose (MTD) of K weekly. 4 cohorts of 6 patients each were recruited at K 36, 45, 56 and 70 mg/m2 on days 1, 8, 15, 22 IV of 35-days cycles, with oral Melphalan and Prednisone from days 1 to 4 at usual doses. Patients received a 9-cycles induction followed by a K monotherapy maintenance at 36 mg/m2 IV every 2 weeks for 1 year. 3 dose-limiting toxicities (DLTs) defined MTD at the lower N-1 dose. Results: 24 patients were included at K 36, 45, 56 and 70 mg/m². One DLT occurred at 36 mg/m² (grade 4 lymphopenia), one at 45 mg/m² (tumor lysis syndrome with grade 4 renal insufficiency), two at 56 mg/m² (grade 3 cardiac insufficiency and grade 3 febrile neutropenia) and two at 70 mg/m² (grade 3 nausea/vomiting and grade 3 hepatic cytolysis). One patient died from cardiac dysfunction considered related to K at 56 mg/m². 3 patients stopped therapy and 3 others required dose reduction of K. Following DSMB’s request a second 6-patients cohort was recruited at 70 mg/m², with increased attention around hyperhydration and monitoring HTA. We observed no DLT and no grade 3/4 adverse event in this cohort. Median age was 75 years, 56% patients were R-ISS 2 or 3. For the whole cohort (N=30), the overall response rate was 87% including 67% very good partial responses and 44% complete responses. Conclusions: The MTD of weekly K in the KMP combination is 70 mg/m² upfront for eNDMM, but it seems reasonable to recommend 56mg/m² after 75 years-old for safety reasons. KMP offers high response rates and possibly greater CR rate. However, since the CLARION study (VMP vs KMP) will not allow KMP’s approval in eNDMM in Europe, IFM decided to stop IFM2012-03 after phase I without performing phase II. Clinical trial information: NCT02302495.
Minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) in newly diagnosed transplant eligible multiple myeloma (MM) patients: Results from the EMN02/HO95 phase 3 trial.
Authors: Oliva Stefania , Hofste op Bruinink Davine , ŘÍhová Lucie , Spada Stefano , van der Holt Bronno , Troia Rossella , Gambella Manuela , Pantani Lucia , Grammatico Sara , Gilestro Milena , Offidani Massimo , Ribolla Rossella , Galli Monica , Hajek Roman , Palumbo Antonio , Cavo Michele , Omedè Paola , van der Velden Vincent , Boccadoro Mario , Sonneveld Pieter 
Published: September 2018

8011 Background: MRD detection is a sensitive tool to measure response in MM. We assessed MRD by MFC in newly diagnosed MM patients (pts) enrolled in the EMN02/HO95 phase 3 trial. Methods: Pts were ≤65 years old and received Bortezomib-Cyclophosphamide-Dexamethasone (VCD) induction, intensification with Bortezomib-Melphalan-Prednisone (VMP) vs High-Dose-Melphalan (HDM) followed by stem cell transplant, consolidation with Bortezomib-Lenalidomide-Dexamethasone (VRD) vs no consolidation, and Lenalidomide maintenance. MRD analysis was performed in pts achieving at least a very good partial response (VGPR) before starting maintenance (after HDM, VMP or VRD) and during maintenance every 6-12 months; samples were centralized to 3 European labs. MFC was performed on bone marrow according to Euroflow-based methods (8 colors, 2 tubes) with a sensitivity of 10-5. Quality checks were performed to compare sensitivity and to show correlation between protocols (Hofste op Bruinink D ASH 2016 abstract 2072). Results: 316 pts were evaluable before maintenance: median age was 57 years, 18% (57/316) pts had ISS III and 22% (70/316) had high risk cytogenetic (HR-C) defined as having at least one among del17, t(4;14) or t(14;16); 63% (199/316) had received HDM and 37% (117/316) VMP; thereafter 51% (160/316) had received VRD. 76% (239/316) were MRD negative (MRD-) of whom 64% (153/239) received HDM vs 36% (86/239) VMP, with a median follow-up time of 30 months from MRD enrolment. 3-year PFS was 50% in MRD positive (MRD+) vs 77% in MRD- pts (HR: 2.87, p < 0.001). Subgroup analyses were performed to evaluate the risk factors for MRD+ according to baseline characteristics and therapies: HR-C was the most important risk factor (HR 9.87, interaction-p = 0.001). Finally, 48% of MRD+ pts at pre-maintenance who had a second MRD evaluation after at least 1 year of lenalidomide became MRD-. Conclusions: MRD by MFC is a strong prognostic factor in MM pts receiving intensification with novel agents or transplant; lenalidomide maintenance further improved depth of response; HR-C is the most important prognostic factor in MRD+ pts. Clinical trial information: NCT01208766.
Evaluation of an oral direct anti-Xa anticoagulant, apixaban, for the prevention of venous thromboembolism in patients with myeloma treated with IMiD* compounds: A pilot study (MYELAXAT).
Authors: Pegourie Brigitte , Pernod Gilles , Karlin Lionel , Benboubker Lofti , Orsini Frederique , Tiab Mourad , Auger-Quittet Sophie , Rodon Philippe , Royer Bruno , Leleu Xavier , Bareau Benoit , Cliquennois Manuel , Fuzibet Jean-Gabriel , Voog Eric , Belhadj Karim , Decaux Olivier , Rey Philippe , Slama Borhane ,   IFM Group
Published: September 2018

8019 Background: The risk of venous thromboembolism (VTE) is higher in myeloma patients recieving IMiD* compounds (IMiD*: registered). A VTE prophylaxis using low-molecular-weight heparin or aspirin is proposed. Apixaban is an oral direct anti-Xa. Several studies have shown the efficiency and safety of apixaban in VTE prophylaxis compared to enoxaparin. The objective of this prospective pilot study was to assess the risk of VTE and bleeding in patients with myeloma treated with IMiD* compounds, using apixaban in a preventive scheme. Methods: Myeloma patients requiring Melphalan-Prednisone-Thalidomide in first line, or Lenalidomide-Dexamethasone in relapse, asymptomatic regarding VTE at inclusion, were enrolled between 2014 - 2016. All patients recieved apixaban, 2.5 mg x 2/day for 6 months, and were monthly monitored. Venous (pulmonary embolism – PE, or symptomatic proximal or distal deep vein thrombosis - DVT, or all proximal asymptomatic events detected by systematic proximal bilateral compression ultrasound) or arterial thrombotic events, and bleeding events (ISTH 2005) were registered. Based on meta-analysis of Carrier regarding VTE recurrence, and results from the ADOPT study in medical conditions regarding hemorrhages, < 13 symptomatic VTE events, < 3 severe and < 14 clinically relevant non major (CRNM) bleeding were expected on the treatment period. Results: 104 patients were enrolled (mean age 69.8 +/- 7.8yrs), 11 in first line, 93 in relapse. No PE or arterial cardiovascular events were reported. Two venous thrombotic events were registered, i.e an asymptomatic proximal DVT (patient in relapse) and a symptomatic distal DVT, although apixaban was stopped 14 days before, due to Lenalidomide-induced thrombopenia. Only one major and 11 CRNM hemorrhages were reported. Conclusions: Referring to the incidence of thromboembolic events in Carrier’s meta-analysis, and to hemorrhagic events in medical patients recieving apixaban in primary VTE prophylaxis, apixaban used in a preventive scheme seems to be efficient and safe in preventing VTE in myeloma patients treated with IMiD* compounds. Clinical trial information: NCT02066454.
Acupuncture for symptom reduction in myeloma patients undergoing hematopoietic stem cell transplantation: A randomized, sham-controlled trial.
Authors: Deng Gary E. , Giralt Sergio , Chung David J. , Landau Heather Jolie , Siman Jonathan , Search Benjamin , Coleton Marci , Vertosick Emily , Shapiro Nathan , Chien Christine , Wang Xin Shelley , Cassileth Barrie R. , Mao Jun J. 
Published: September 2018

8021 Background: Hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for a number of hematologic malignancies, but is associated with a high symptom burden for patients. We conducted a randomized sham-controlled trial to evaluate the preliminary efficacy and safety of acupuncture as an integrative treatment for managing common symptoms during HCT. Methods: Adult patients with multiple myeloma undergoing high dose melphalan followed by autologous peripheral blood HCT were randomized to receive either true or sham acupuncture once daily for five days starting on the day after chemotherapy. Symptom burden was assessed with the MD Anderson Symptom Inventory (MDASI) at baseline, during transplantation, and at 15 and 30 days after transplantation. Results: Among 60 participants, symptoms that are significantly reduced by true acupuncture more than sham acupuncture at 15 days include the following: nausea, lack of appetite, and drowsiness (p = 0.042, 0.025, and 0.010, respectively). Patients receiving sham acupuncture were more likely to increase use of pain medication post-transplantation (odds ratio 5.31, p = 0.017). Acupuncture was well tolerated with few attributable adverse events. Conclusions: True acupuncture may prevent escalation of symptoms including nausea, lack of appetite, and drowsiness experienced by patients undergoing autologous HCT, and to reduce the use of pain medications. These findings need to be confirmed in a future definitive study. Clinical trial information: NCT01811862.
Pomalidomide (POM) + low-dose dexamethasone (LoDEX) after lenalidomide (LEN)-based second-line (2L) treatment (Tx) in patients (Pts) with relapsed/refractory multiple myeloma (RRMM): Analysis of progression-free survival (PFS) by level of disease control.
Authors: Siegel David , Schiller Gary J. , Song Kevin W. , Agajanian Richy , Stockerl-Goldstein Keith , Kaya Hakan , Sebag Michael , Reu Frederic J. , Malek Ehsan , Talamo Giampaolo , Mouro Jorge L , Chung Weiyuan , Srinivasan Shankar , Qian Max , Rizvi Syed , Thakurta Anjan , Bahlis Nizar J. 
Published: September 2018

8027 Background: Recent trials of triple therapy in 2L and third-line (3L) Tx excluded pts refractory to LEN. This is not reflective of standard of care in first line and 2L where LEN is given until progressive disease (PD). MM-014 enrolled pts with RRMM and 2L LEN-based Tx failure. Here we report results only from cohort A of pts receiving POM + LoDEX. Cohort B will investigate POM + LoDEX + daratumumab. Methods: Adult pts with MM, 2 prior Tx lines, and PD after ≥ 2 cycles of 2L LEN-based Tx received POM + LoDEX. The primary endpoint was overall response rate (ORR). Other endpoints included time to response (TTR), PFS, second primary malignancies (SPMs), and biomarkers. Results: Of 51 pts in cohort A, 39 (76.5%) discontinued Tx. Most pts (88.2%) were refractory to their last LEN Tx, (median Tx duration 24.6 mos) and 72.5% had prior bortezomib. At a median follow-up of 13.6 mos, ORR was 29.4% (2.0% complete response, 9.8% very good partial response, and 17.6% partial response [PR]) and median TTR was 1.9 mos; 66% of pts had ongoing response at 1 yr. Minimal response [MR] was reached in 15.7%. Median PFS was 13.8 mos. Pts with ≥ MR had similar Tx durations as those achieving ≥ PR. Additional results in Table. Post-Tx T-cell populations were significantly higher vs baseline (CD3+, 72.6% vs 67.8%; CD3+/CD8+, 36.9% vs 32.1%). Relative changes from baseline were significantly greater in pts with response vs pts with no response (CD3+, 10.4 vs −0.8; CD3+/CD4+, 4.2 vs −3.5). Conclusions: This update confirms the safety and efficacy of POM + LoDEX following 2L LEN-based Tx failure in pts with RRMM. Hematologic adverse event (AE) rates improved and median PFS was longer with 3L use than previously reported with POM + LoDEX use in later Tx lines. In addition, achieving disease control of ≥ MR led to similar PFS rates as reaching ≥ PR. Clinical trial information: NCT01946477. [Table: see text]
Safety and efficacy of daratumumab-based regimens in elderly (≥75 y) patients (Pts) with relapsed or refractory multiple myeloma (RRMM): Subgroup analysis of POLLUX and CASTOR.
Authors: Mateos Maria-Victoria , Spencer Andrew , Nooka Ajay K. , Pour Ludek , Weisel Katja C. , Cavo Michele , Laubach Jacob , Cook Gordon , Iida Shinsuke , Benboubker Lotfi , Usmani Saad Zafar , Yoon Sung-Soo , Bahlis Nizar J. , Chiu Christopher , Schecter Jordan Mark , Wu Kaida , Qin Xiang , Soong David , Dimopoulos Meletios A. 
Published: September 2018

8033 Background: Daratumumab (D) plus lenalidomide and dexamethasone (Rd; POLLUX) or with bortezomib and dexamethasone (Vd; CASTOR) demonstrated prolonged PFS and tolerability compared with Rd and Vd alone, respectively, in RRMM pts. We examined the safety and efficacy profiles of DRd and DVd in elderly (≥75 y) pts from these phase 3 studies. Methods: Pts with ≥1 prior line of therapy were enrolled. All pts in POLLUX were treated until progression; CASTOR pts received 8 cycles of Vd ± daratumumab. Different D (16 mg/kg) dosing schedules were used in POLLUX (qw for cycles 1-2, q2w for cycles 3-6, and q4w thereafter) and CASTOR (qw in Cycles 1-3, q3w for Cycles 4-8, and q4w thereafter). Elderly pts received a reduced dexamethasone dose (20 mg once weekly). Results: In POLLUX, 29/286 (DRd) and 35/283 (Rd) were ≥75 y, with 86% and 91% having ECOG status ≤1, respectively. With 17.3 months of median follow up, 10% in DRd and 11% in Rd discontinued due to treatment-emergent adverse events (TEAEs). Common (>10%) grade 3/4 TEAEs for DRd included neutropenia and hypokalemia (Table). Twelve (41%) DRd pts experienced infusion-related reactions (IRR) and 4 (14%) experienced grade 3/4 IRR; none discontinued due to IRR. Median PFS was not reached (NR) in DRd vs 11.4 months in Rd (HR 0.19; 95% CI, 0.06-0.55; P=0.0007), and ≥CR % was significantly higher with DRd vs Rd (52% vs 9%; P=0.0002). In CASTOR, 23/251 (DVd) and 35/247 (Vd) were ≥75 y, with 100% and 94% having ECOG status ≤1, respectively. With 13.0 months of median follow up, rates of discontinuation due to TEAEs were similar (15% vs 20%). Thrombocytopenia, fatigue, and pneumonia were common grade 3/4 TEAEs for DVd (Table). Thirteen (65%) pts reported IRR (10% grade 3/4) and no pts discontinued due to IRR. Median PFS was NR in DVd vs 8.1 months in Vd (HR 0.27; 95% CI, 0.12-0.61; P=0.0007), and significantly higher ≥CR % was observed in DVd vs Vd (25% vs 3%; P=0.0154). Conclusions: The safety and efficacy profiles in elderly pts were generally comparable with the overall population in each study. Clinical trial information: NCT02136134 and NCT02076009. [Table: see text]
Safety and feasibility of consolidation pembrolizumab following concurrent chemoradiation for unresectable stage III non-small cell lung cancer: Hoosier Cancer Research Network LUN14-179.
Authors: Durm Greg Andrew , Johnson Cynthia , Jalal Shadia Ibrahim , Sadiq Ahad Ali , Jabbour Salma , Zon Robin , Kloecker Goetz H. , Reckamp Karen L. , Fisher William B. , Hanna Nasser H. 
Published: September 2018

8523 Background: The standard of care for unresectable stage III NSCLC is concurrent chemorad. Following treatment, the risk of radiation pneumonitis is greatest at 1-3 mo. Pneumonitis risk increases with consolidation chemotherapy. A previous trial by our group (Hanna et al, JCO 2008) of consolidation docetaxel showed 80.8% completed 3 planned cycles of chemo with a grade 3-5 pneumonitis rate of 9.6% and 1 death. PD-1 inhibitors are also associated with an increased risk of pneumonitis in the metastatic setting. We conducted a phase II trial of consolidation pembro initiated 1-2 mo after concurrent chemorad, a period during which pts are at high risk of developing pneumonitis. Methods: Pts with stage III NSCLC who completed chemorad with either carbo/paclitaxel, cis/etop, or cis/pemetrexed plus 59-66.6 Gy of radiation and had no PD received pembro 200mg IV q3wk for up to 1 yr. Primary endpoint is time to metastatic disease. The objective of the study is to evaluate both safety and efficacy, and here we report preliminary safety and feasibility results. Evaluable pts for this analysis had ≥3 mo of f/u or went off study due to PD, toxicity, or death < 3 mos after initiation of pembro. Results: 93 pts enrolled. Median age 67 (range 46-84), 59 (63.4%) were male. 87 (93.5%) were former or current smokers. 68 (73.1%) received carbo/pac, 24 (25.8%) received cis/etop, and 1 received cis/pemetrexed. SqCC (n = 41), non-SqCC (n = 43), NSCLC NOS (n = 8), mixed (n = 1). IIIA (n = 56), IIIB (n = 37). At the time of analysis, 83 of 93 pts were evaluable. 66 of 83 (79.5%) received ≥ 3 mo of pembro. 17 (20.5%) pts developed any grade pneumonitis with 14 of 17 occurring in the first 12 wks (median 9 wks). Only 3 (3.6%) pts developed grade 3-5 pneumonitis related to pembro. There was 1 pneumonitis-related death and a second death from respiratory failure possibly related to pembro. Conclusions: This early report indicates that most patients can safely receive consolidation pembro within 1-2 mo of completing chemorad. The incidence of serious pneumonitis during the first 3 mo of treatment appears low. Updated safety data on all 93 pts will be presented at the ASCO meeting. Clinical trial information: NCT02343952.
A multicenter, randomized, open-label, phase II trial of erlotinib versus etoposide plus cisplatin with concurrent radiotherapy in unresectable stage III non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) activating mutation.
Authors: Xing Ligang , Wu Gang , Wang Lvhua , Li Jian-Cheng , Wang Jianhua , Yuan Zhiyong , Chen Ming , Xu Yaping , Zhu Zhengfei , Lu You , Han Chun , Xia Tingyi , Xie Conghua , Li Guang , Yu Jinming 
Published: September 2018

8531 Background: Concurrent chemoradiotherapy is the standard treatment for patients(pts) with unresectable stage IIIA/IIIB NSCLC. In EGFR mutant pts, tyrosine kinase inhibitor(TKI) exhibits clinical benefits over chemotherapy regimens in terms of efficacy and safety as well as specific enhancement of radiation effects. This multicenter, randomized, open-label, phase II trial aimed to compare the erlotinib and etoposide/cisplatin with concurrent radiotherapy (RT) in pts with EGFR-mutant. Methods: Histopathology/cytology confirmed stage IIIA/B unresectable NSCLC pts (age 18-75) with ECOG PS 0-1 and EGFR exon 19 or 21 mutation were included and randomized (1:1) into two arms: erlotinib (E) and etoposide/cisplatin (EP). E arm was treated with oral erlotinib (150mg/day for 2 years or till either disease progression or intolerable toxicities) and RT (200cGy/day, 5 days/week for 6 weeks from first day erlotinib). EP arm was treated with sequential etoposide (50 mg/m2 IV days 1-5, 29-33) and cisplatin (50mg/m2IV day 1,8, 29,36) and RT (from first day drug). Primary endpoint is progress free survival (PFS). Secondary endpoints are objective response rate(ORR), local control rate(LCR), overall survival(OS), quality of life(QoL) and safety. Results: 252 pts were screened, and 41 were enrolled into E(n=20) and EP(n=21) arms. Characteristics of age, sex, histologic type, N2, EGFR 19 and 21 mutation were well balanced in each arm. Comparing with EP, median PFS of E arm was significantly improved (27.86 vs 6.41 months; HR 0.053, 95% CI: 0.006-0.463; P<0.001). ORR and DCR were 60.0% vs. 38.1%( P=0.217), and 65% vs. 47.6%( P=0.350), respectively. Two arms had same incidence of adverse effects (CTCAE Grade≥1, 86.7%[13/15]), and most common sAE(Grade≥3) was rash (20%, 3/15) and hematological toxicity(26.7%, 4/15), respectively. Conclusions: In unresectable stage III EGFR mutant NSCLC pts, concurrent erlotinib/RT provides a statistically significant PFS improvement with well tolerability. These results warrant a phase III study to confirm. (RECEL, NCT01714908). Clinical trial information: NCT01714908.