bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary results of PI3Kδ inhibitor idelalisib (GS-1101) treatment in combination with everolimus, bortezomib, or bendamustine/rituximab in patients with previously treated mantle cell lymphoma (MCL).
Authors: Wagner-Johnston Nina D. , De Vos Sven , Leonard John , Sharman Jeff Porter , Schreeder Marshall T. , Boccia Ralph V. , Barrientos Jacqueline Claudia , Coutre Steven E. , Flinn Ian , Boyd Thomas E. , Holes Leanne , Johnson David Michael , Kim Yeonhee , Dansey Roger D. , Godfrey Wayne R. , Fowler Nathan Hale 
Published: March 2020

8501 Background: PI3K-delta 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 that has shown monotherapy activity in recurrent MCL (Kahl, ICML 2011). Methods: This phase 1 study is evaluating the activity of continuous idelalisib (Id), 150 mg BID, in combination with everolimus (E) (10 mg PO qD) (Id+E regimen), with bortezomib (V) (1.3 mg/m2 SC day 1, 8, 15 per 28 day cycle) (Id+V regimen), or with rituximab (R) (375 mg/m2, on Day 1) and bendamustine (B) (90 mg/m2x 2), for 6 cycles (Id+BR regimen). Investigators assessed response according to standard criteria (Cheson 2007). Results: Study enrolled 22 patients with relapsed/refractory MCL. Results are from 14 Jan 2013 data cutoff. The 3 cohorts included Id+E (N=12), Id+V (N=6), and Id+BR (N=4). Patients were 73% male, median age [range] of 68 [47E79] years, 32% with refractory disease and 73% stage III/IV. The median [range] number of prior therapies was 3 [1E7]. The median [range] duration of treatment was 2.5 [0.5-8.3+] months. Overall response rate (ORR) was 10/22 (46%), with 2 CR (9%). The ORR/CR for Id+E, was 25%/0%, Id+V was 50%/0%, and Id+BR was 100%/50%. The median duration of response (mDOR) and median PFS (mPFS) were not reached. Most common adverse events included (total%/≥G3%) diarrhea (41/9), fatigue (41/0), rash (27/14), cough (27/0), decreased appetite (23/0), and epistaxis (23/0). Lab abnormalities included (total%/≥G3%) thrombocytopenia (82/27), neutropenia (32/14), and ALT/AST elevations (50/5). Conclusions: Preliminary data indicates idelalisib-based combination therapy is active in patients with relapsed/refractory MCL. All combinations were tolerable. These data support further clinical development in larger trials to further characterize safety and response duration. Clinical trial information: NCT01088048.
MM-003: A phase III, multicenter, randomized, open-label study of pomalidomide (POM) plus low-dose dexamethasone (LoDEX) versus high-dose dexamethasone (HiDEX) in relapsed/refractory multiple myeloma (RRMM).
Authors: San-Miguel Jesùs F. , Weisel Katja C. , 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. , Dimopoulos Meletios A. 
Published: March 2020

8510 Background: RRMM patients (pts) who have exhausted treatment (Tx) with bortezomib (BORT) and lenalidomide (LEN) or thalidomide have a poor prognosis with short overall survival (OS). HiDEX is a well-established standard Tx in RRMM. POM has demonstrated clinical efficacy in pts refractory to LEN and BORT. MM-003 compared POM + LoDEX vs. HiDEX in RRMM pts who failed LEN and BORT and who progressed on their last Tx. Methods: Pts must have been refractory to last prior Tx (progressive disease [PD] during Tx or within 60 days) and failed LEN and BORT after ≥ 2 consecutive cycles of each (alone or in combination). Pts were randomized 2:1 to receive 28-day cycles of POM 4 mg D1–21 + DEX 40 mg (20 mg for pts aged > 75 y) weekly or DEX 40 mg (20 mg for pts aged > 75 y) D1–4, 9–12, and 17–20. Tx continued until PD or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included OS, overall response rate (ORR; ≥ partial response), and safety. Analyses were based on intent to treat. Results: 455 pts were randomized to POM + LoDEX (n = 302) or HiDEX (n = 153). The median number of prior Tx was 5 (range 1-17). 72% were refractory to LEN and BORT. Median follow-up was 4 months. POM + LoDEX significantly extended median PFS (3.6 vs. 1.8 months, HR = 0.45, P < .001) and OS (not reached vs. 7.8 months, HR = 0.53, P < .001) vs. HiDEX. The OS benefit was observed despite 29% of HiDEX pts receiving POM after PD. The trial met the primary endpoint of PFS, crossed the upper boundary for OS superiority, and the Data Monitoring Committee recommended crossover from HiDEX to POM ± DEX. With updated data, the ORR was 21% for POM + LoDEX vs. 3% for HiDEX (P < .001) and 24% vs 3% for pts randomized ≥ 6 months post-enrollment (P < .001). The most frequent grade 3/4 adverse events (AEs) for POM + LoDEX vs. HiDEX were neutropenia (42% vs. 15%), anemia (27% vs. 29%), and infection (24% vs. 23%). Discontinuation due to AEs was infrequent (7% vs. 6%). Updated data will be presented. Conclusions: POM + LoDEX significantly extended PFS and OS vs. HiDEX in pts who failed LEN and BORT. POM + LoDEX should become a standard of care in RRMM pts who have exhausted Tx with LEN and BORT. Clinical trial information: NCT01311687.
Lenalidomide in relapsed/refractory mantle cell lymphoma post-bortezomib: Subgroup analysis of the MCL-001 study.
Authors: Williams Michael E. , Goy Andre , Sinha Rajni , Kalayoglu Besisik Sevgi , Drach Johannes W. , Ramchandren Rod , Zhang Lei , Cicero Sherri , Fu Tommy , Witzig Thomas E 
Published: March 2020

8534 Background: Lenalidomide, an immunomodulatory agent with antitumor and antiproliferative effects, demonstrated rapid and durable efficacy in patients with relapsed/refractory mantle cell lymphoma (MCL) post-bortezomib in the phase II multicenter MCL-001 study. The objective of this analysis was to explore the efficacy of lenalidomide across patient subgroups. Methods: Single-agent lenalidomide was administered at 25 mg/d PO on days 1-21 of a 28-day cycle until disease progression or intolerability; primary endpoints were overall response rate (ORR) and duration of response (DOR) determined by an independent central review committee per modified IWG criteria. Exploratory analyses of ORR and DOR for subgroups were predefined and prospectively conducted. Results: Patients with relapsed/refractory MCL (N=134) had a median age of 67 y, with a median of 4 prior therapies (range, 2-10). The ORR was 28% (7.5% CR/CRu) and DOR was 16.6 months (95% CI, 7.7-26.7). Lenalidomide treatment provided consistent ORR and DOR across all subgroups analyzed by demographics, baseline disease status and prior therapy (Table). High vs normal baseline LDH was the only significant factor by univariate and multivariate logistic regression analysis of ORR (odds ratio=0.193; p=0.002). Conclusions: Single-agent lenalidomide provided consistent clinical benefit in patients with relapsed/refractory MCL post-bortezomib irrespective of patient subgroups at baseline with the exception of LDH. Clinical trial information: NCT00737529. [Table: see text]
Secondary efficacy subanalysis by histology from the phase III BRIGHT study: First-line bendamustine-rituximab (BR) compared with standard R-CHOP/R-CVP for patients with advanced indolent non-Hodgkin lymphoma (NHL) or mantle cell lymphoma (MCL).
Authors: Flinn Ian , Van Der Jagt Richard H. C. , Kahl Brad S. , Wood Peter , Hawkins Tim E. , MacDonald David , Hertzberg Mark , Kwan Yiu-Lam , Simpson David , Craig Michael , Kolibaba Kathryn S. , Issa Samar , Clementi Regina , Hallman Doreen M. , Munteanu Mihaela C. , Chen Ling , Burke John M. 
Published: March 2020

8537 Background: BR was previously reported to be statistically noninferior to R-CVP/R-CHOP for complete response rate in the treatment of patients with indolent NHL or MCL. Evaluation of time-to-event outcomes is immature. This subanalysis reports response by histology. Methods: Indolent NHL or MCL was histologically confirmed <6 months before study enrollment in patients who were therapy-naïve. Patients were stratified according to predetermined standard treatment (R-CHOP or RECVP) and lymphoma type, then assigned to receive BR (28-day cycles: bendamustine 90 mg/m2 on days 1 and 2, rituximab 375 mg/m2on day 1) or standard treatment (21-day cycles at standard doses) for 6-8 cycles. Responses were assessed by a blinded independent review committee. The primary efficacy measure was noninferiority of BR complete response (CR) rate for evaluable patients with ≥1 postbaseline efficacy assessment. If the noninferiority threshold was met, superiority was assessed. Secondary measures included tolerability. Results: Of 447 patients enrolled in the study, 213 receiving BR and 206 receiving R-CHOP/R-CVP were evaluable with postbaseline data (Table). BR achieved a statistically noninferior CR rate compared with R-CHOP/R-CVP in patients with indolent NHL and MCL. Conclusions: In patients with treatment-naïve indolent NHL and MCL, BR achieved the primary endpoint of noninferior CR rate. Most CR rates were numerically, but not significantly, higher with BR. Small subgroup results should be interpreted with caution. Support: Teva BPP R&D, Inc. Clinical trial information: NCT00877006. [Table: see text]
Early versus delayed autologous stem cell transplant (ASCT) in patients receiving induction therapy with lenalidomide, bortezomib, and dexamethasone (RVD) for newly diagnosed multiple myeloma (MM).
Authors: Nooka Ajay K. , Langston Amelia A. , Waller Edmund K. , Heffner Leonard T. , Gleason Charise , Muppidi Samatha , Watson Melanie , Casbourne Daniela , Boise Lawrence , Kaufman Jonathan L. , Lonial Sagar 
Published: March 2020

8540 Background: Lenalidomide, bortezomib and dexamethasone (RVD) is an active, tolerable induction regimen with superior response rates (≥VGPR rates of 80%) in newly diagnosed MM pts. However, the optimal timing of ASCT with this triplet combination is uncertain. We have evaluated our institutional experience to provide an insight for the best timing of ASCT, where specific patients were offered delayed ASCT based on risk, response and toxicity of therapy. Methods: 222 consecutive transplant-eligible pts with newly diagnosed MM that received at least 3 cycles of RVD and harvested stem cells were included in the analysis from May 2007 until October 2011. Patients underwent early ASCT (received planned ASCT immediately after stem cell harvest, n=136) or delayed transplant (received planned maintenance therapy after collection with intent to proceed with ASCT at first relapse, n=86). Results: Median age of the patients at the time of diagnosis is 60.5 yrs (32-77) vs. 60 yrs (22-73) for early vs. delayed groups. ISS stage 3 disease was seen in 31% patients and 10% patients; high risk cytogenetics were seen in 11% and 7% patients in early vs. delayed groups, respectively. Median time from initiation of induction therapy to ASCT in early group is 5.45 months (range, 3.19-12.68 months). In the delayed SCT group, 28 patients underwent ASCT at a median time of 26.21 months (range, 13.67-41.72 months) from initiation of therapy. At a median follow up of 32 months, 5-year overall survival from diagnosis was 68% and 88% in patients undergoing early and delayed ASCT, respectively (p = 0.106). Conclusions: Transplantation-eligible patients who receive RVD as initial therapy followed by early vs. delayed ASCT result in comparable overall survival. In carefully selected newly diagnosed myeloma patients with lower ISS stage receiving RVD as induction therapy, planned delayed ASCT results in 5-year survival rates close to 90%.
Lenalidomide (LEN)-melphalan-prednisone induction followed by LEN maintenance (MPR-R) in newly diagnosed multiple myeloma (NDMM) elderly patients (Pts) with moderate renal impairment (RI): MM-015 trial post-hoc analysis.
Authors: Catalano John V. , Palumbo Antonio , Weisel Katja C. , Dimopoulos Meletios A. , Delforge Michel , Blade Joan , Petrucci Maria Teresa , Kropff Martin , Hajek Roman , Jacques Christian , Yu Zhinuan , Herbein Lindsay , Cavo Michele 
Published: March 2020

8544 Background: The MM-015 pivotal phase III trial showed significant PFS benefit for MPR-R (31 mos) vs. MPR (14 mos) or MP (13 mos; both p < 0.001) followed by placebo in NDMM pts aged ≥ 65 years. As NDMM pts with RI have poor prognosis, this retrospective analysis studied the efficacy and safety of MPR-R in pts with creatinine clearance (CrCl) < 60 mL/min. Methods: LEN starting dose for induction/maintenance was 10 mg/day (D1–21 of a 28-day cycle). Dose adjustments were not recommended for pts with RI. CrCl was calculated using the Cockcroft-Gault equation. Pts with severe RI (serum Cr > 2.5 mg/dL [221 μmol/L]) were excluded from the trial. Results: Pts with CrCl < 60 mL/min (median 47, interquartile range [IQR] 38–55) were included in this analysis: 51% MPR-R, 45% MPR, and 49% MP. Median PFS was significantly higher with MPR-R (26 mos [95% CI 14–48]) vs. MPR (13 mos [95% CI 12–15]) or MP (14 mos [95% CI 12–16]; both p < 0.001). In a Cox proportional model of PFS, CrCl < 60 mL/min was not identified as a negative prognostic factor (p = 0.69). The most common Gr 4 adverse events (AEs) were hematologic and occurred predominantly during induction and are shown in the Table for pts with or without moderate RI. The number of deaths on study was similar: 10% (MPR-R), 7% (MPR), and 8% (MP); deaths associated with RI or disease progression were reported in ≤ 1% of pts with RI across the arms. Conclusions: The benefit of continuous LEN treatment with MPR-R is not compromised in NDMM pts with moderate RI, consistent with the overall trial results. CrCl and AEs should be monitored closely in this population. Clinical trial information: NCT00405756. [Table: see text]
Results after long-term follow-up from the CAN2007 phase I/II study of weekly or twice-weekly bortezomib in patients (pts) with relapsed systemic light-chain (AL) amyloidosis.
Authors: Reece Donna Ellen , Hegenbart Ute , Sanchorawala Vaishali , Merlini Giampaolo , Palladini Giovanni , Blade Joan , Fermand Jean-Paul , Hassoun Hani , Heffner Leonard , Pei Lixia , Enny Christopher , Esseltine Dixie , Van De Velde Helgi , Cakana Andrew , Comenzo Raymond 
Published: March 2020

8545 Background: Data from multiple studies suggest that bortezomib alone or in combination regimens is active in newly diagnosed and relapsed AL. CAN2007 (NCT00298766) was the first prospective study of single-agent bortezomib in relapsed AL. Here we report outcome data at study closure after a median follow-up of 51.8 mos (median 46.1–66.1 mos). Methods: 70 pts received bortezomib 0.7, 1.0, 1.3, or 1.6 mg/m2 on days 1, 8, 15, and 22 of 35-day cycles (QW) or 0.7, 1.0, or 1.3 mg/m2 on days 1, 4, 8, and 11 of 21-day cycles (BIW) for up to 8 cycles (or longer in pts with evidence of ongoing clinical benefit). The maximum tolerated dose was not reached on either schedule; 18 and 34 pts were treated at the maximum planned doses of 1.6 mg/m2 QW and 1.3 mg/m2BIW, respectively, and 18 pts were treated at lower doses. Post-treatment, pts were followed every 6 weeks until disease progression, and then every 3 mos for survival during the long-term follow-up phase. Results: Pts received a median (range) of 8 (1–39), 6 (1–57), and 8 (3–57) cycles of bortezomib in the 1.6 mg/m2 QW, 1.3 mg/m2 BIW, and lower-dose groups, respectively; overall, 32 (46%) pts received ≥8 cycles, and 4 pts were still on treatment and had received ≥39 cycles at study closure. Hematologic responses and outcomes are summarized below. Median (range) follow-up for survival was 51.8 (1–68), 46.1 (1–61), and 66.1 (2–80) mos, and 7, 12, and 9 pts have died, in the 1.6 mg/m2 QW, 1.3 mg/m2BIW, and lower-dose groups, respectively. Median overall survival (OS) in all 70 pts was 62.7 mos, and 4-yr OS rate was 67.3%; data by dose group are shown below. Conclusions: Single-agent bortezomib produces durable hematologic responses and promising long-term OS data in pts with relapsed AL. Clinical trial information: NCT00298766. [Table: see text]
Patterns of failure in advanced-stage diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP chemotherapy and the emerging role of consolidative radiotherapy.
Authors: Shi Zheng Jane , Das Satya , Okwan-Duodu Derick , Esiashvili Natia , Flowers Christopher , Jiang Kun , Chen Zhengjia , Wang Xiaojing , Curran Walter J. , Khan Mohammad K. 
Published: March 2020

8546 Background: The role of consolidative radiotherapy (RT) after a complete response (CR) to R-CHOP for stage III-IV DLBCL patients is unclear. The goal of our study is to evaluate the Emory experience when consolidative RT is delivered to initial presenting nodal and extranodal sites or bulky sites in these patients. Methods: From 01/2000 to 05/2012, 211 histologically confirmed DLBCL patients with stage III-IV disease who received R-CHOP were identified at Emory University. Patterns of failure for patients who achieved CR to R-CHOP were analyzed. Local control (LC), distant control (DC), progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method and compared between patients who received R-CHOP alone versus R-CHOP plus consolidative RT using Log-rank test. Multivariate analyses were also performed using Cox proportional hazards model. Results: 163 patients had detailed treatment records. After a median 6 cycles of R-CHOP, 110 patients (67.5%) achieved CR and were entered for analysis. Fourteen patients (12.7%) received consolidative RT to a median dose of 30.6 Gy as part of initial management. With a median follow up time of 32.9 months, 43.8% of patients who received R-CHOP alone failed at the initial presenting sites with or without distant recurrence (DR), whereas isolated DR only occurred in 3.2% of these patients. Consolidative RT was associated with significantly improved LC (91.7% vs 48.8%, p<0.0001), DC (92.9% vs 71.9%, p<0.0001), PFS (85.1% vs 44.2%, p<0.0001) and OS (92.3% vs 68.5%, p<0.0001) at 5-years when compared to patients with R-CHOP alone. In addition, the in-field control rate was 100% within irradiated sites for patients who received consolidative RT. On multivariate analysis, consolidative RT and non-bulky disease were predictive of increased LC and PFS, whereas bone marrow involvement was associated with increased risk of DR and worse OS. Conclusions: 44% of patients with advanced stage DLBCL failed at initial presenting sites despite achieving a CR to R-CHOP. Incorporation of consolidative RT as part of upfront treatment in these patients was associated with improved LC and PFS.
Nodular lymphocyte-predominant and classical Hodgkin lymphoma subtypes: Differences in biology, survival, and impact of radiotherapy.
Authors: Ali Shihab , Olszewski Adam J. 
Published: March 2020

8550 Background: Hodgkin lymphoma (HL) is a heterogeneous disease, but differences between nodular lymphocyte predominant (NLPHL) and classical (CHL) subtypes were previously studied in small cohorts preventing adjustment for confounders. We studied those differences based on the Surveillance, Epidemiology and End Results (SEER) program data. Methods: We analyzed SEER HL cases aged 16 years and over, diagnosed between 1995 and 2009. We studied the following endpoints: crude probability of HL-related death (HLRD), relative survival (using individual data in multivariate flexible parametric models) and risk of secondary malignancies (using competing risk regression). We studied the impact of radiotherapy (RT) in early-stage disease using a propensity score, adjusting for treatment selection and immortal time bias. Results: We identified 25,903 patients, with disparate age, race and stage distributions between subtypes. In a multivariate model, NLPHL demonstrated significantly better crude and net survival outcomes (Table), but in contrast to all CHL subtypes, it showed a steady increase in mortality rate after 2 years. The risk of secondary non-Hodgkin lymphoma was significantly higher in both NLPHL (hazard ratio, HR, 2.28, P=0.002) and lymphocyte-rich (LR) CHL (HR 2.08, P=0.01) than in nodular sclerosis (NS). The risk of other secondary malignancies did not differ between subtypes. After balancing confounding factors in treatment arms, RT in stage I/II was associated with improved survival in NS (HR, 0.78, P=0.001) and LR-CHL (HR 0.36, P<0.001), but not in NLPHL (HR 0.98, P=0.94) or in the remaining CHL subtypes. Conclusions: Studies of NLPHL and CHL subtypes should account for their disparate biology and clinical course. Prospective evaluation of NLPHL treatment strategies without RT is justified. [Table: see text]
Interim FDG PET/CT to predict progression-free survival (PFS) better than clinical and baseline metabolic measurements in Hodgkin lymphoma (cHL).
Authors: Knight-Greenfield Ashley , Marshall Richard Aaron , Hutchings Martin , Doucette John , Stern Jamie , Coleman Morton , Kostakoglu Lale 
Published: March 2020

8555 Background: Previous studies in cHL have demonstrated that conventional methods to risk stratify patients into various prognostic groups and predict PFS may not be sufficient to individualize therapy. Metabolic parameters using FDG-PET may be helpful for developing a prognostic algorithm and predict PFS. Objectives: To determine the best predictor of PFS among various variables of tm metabolic measurements at baseline and at interim PET/CT compared to conventional methods in cHL patients. Methods: Retrospective evaluation of prospectively acquired data in 58 cHL pts, all stages [IIB-IV:41%, >IPS-3:24%, unfavorable (UF):44%]. Eligibility: PET/CT prior to and after 1 cycle (PET1) ABVD therapy, imaging at 60min+15min, follow-up>24 mo. Baseline PET parameters including metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUVmax, and SULpeak were determined using gradient method (PETVCAR2, GE Healthcare, WI). Data were also evaluated at PET1 for %ΔMTV, %ΔSUVmax, %ΔTLG, PERCIST criteria and visually with Deauville 5-PS. Variables were correlated with PFS. Results: Median follow-up: 32.2 mo. Of 58 pts 14 relapsed (median PFS:6.5 mo). Results for PFS are displayed in the Table. No baseline conventional (stage, IPS, UF vs F) or PET variable was associated with PFS. The best predictor of PFS was Deauville 5-PS at PET1. PERCIST and %ΔTLG using gradient method trended toward significance. Conclusions: Deauville 5-PS best predicts PFS at PET1 in cHL. Neither baseline PET nor conventional prognostic factors correlated with PFS in this group of cHL pts. Risk-stratification of cHL using tumor metabolic volumetry and PERCIST criteria may require a larger sample size and further assessment of various methodologies. [Table: see text]