bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of use of CNS prophylaxis in DLBCL in a large health system.
Authors: Thompson Michael A. , Yoder Sol Atienza , Robinson Lisa Ann , Aranda Renee 
Published: September 2018

7562 Background: Diffuse large B-cell lymphoma (DLBCL) patients (pts) with risk factors based on the R-IPI (Sehn et al. 2007 http://ow.ly/k4Xu308hsBM) and CNS IPI (Schmitz et al. 2016 http://ow.ly/dZIb301YyQ4 ) may relapse in the central nervous system (CNS). NCCN Guidelines (v2.2016) rec lumbar puncture (LP) if 4-6 risk factors present or HIV, testicular, breast, or double expresser and notes optimal management is uncertain. We wished to evaluate the use of CNS px in a large community health system. Methods: The Aurora Health Care cancer registry was searched for DLBCL from 1/1/16 to 12/31/16. Pts with CNS px were selected for more detailed analysis for stage, Myc, R-IPI, CNS IPI and cost of px. CNS px was categorized as: 1) intravenous (IV) high dose methotrexate (HD MTX), 2) IT chemo via Ommaya, or 3) IT via LP. Outcomes were CNS px utilization, survival, and costs. Results: 146 DLBCL pts were treated (5 R-CHOP, 2 DA-R-EPOCH). CNS px was given in 7/146 (4.8%). Pts were 5 males, 2 females. Median age was 58, (range: 38-76). Median R-IPI was 2.4 (range: 0-5). Median CNS IPI was 2.7 (range: 0-5). HD MTX was used in 3 pts. IT was used in 4 pts, with 0 by Ommaya and 4 by LP. Except for one death, there was no CNS or other recurrences yet. Costs per cycle were (drug + administration): 1) HD MTX: $587+ 3166 (hospitalization and leucovorin) = $3753, 2) IT Ommaya: $20 + 921 = $941 (not including Ommaya surgery), 3) IT LP: $20 + 2460 (includes interventional radiology) = $2480. Conclusions: CNS px rate was low across a range of stages and risk scores, which potentially reflects lack of recognition of risk as well as uncertainly about the value including utility (risk reduction) vs cost ($ and pt toxicity). Evaluating for improved utility is necessary, such as lenalidomide (a small molecule with CNS penetration) in R2CHOP (Ayed et al. 2016 http://ow.ly/6s5d308G4I4 ). If that 6 fold risk reduction holds, the value may be high for lenalidomide added to high risk CNS IPI DLBCL pts therapy. [Table: see text]
An open-label, single arm, phase IIa study of bortezomib, lenalidomide, dexamethasone, and elotuzumab in newly diagnosed multiple myeloma.
Authors: Laubach Jacob , Nooka Ajay K. , Cole Craig , O'Donnell Elizabeth , Vij Ravi , Usmani Saad Zafar , Orloff Gregory Joshua , Richter Joshua Ryan , Redd Robert , DiPietro Heidi , Cummings Kristen , Hansen Joshua , Henrick Patrick M. , Bassett Paul , Schachter Haley , Richardson Paul G. , Lonial Sagar 
Published: September 2018

8002 Background: Elotuzumab (elo) is approved for use in combination with lenalidomide (len) and dexamethasone (dex) for relapsed and refractory multiple myeloma (MM). This phase 2a study evaluated the efficacy and safety of elo in combination with len, subcutaneous bortezomib (bortez), and dex. Methods: The primary objective of this study was to determine the response rate of newly diagnosed, transplant-eligible MM patients (pts) after four cycles of therapy with elo plus len, bortez, and dex. Pts were newly diagnosed with MM by the revised IMWG criteria. Elo was administered days 1, 8, and 15 of the first two 28 day cycles and days 1 and 11 in cycles 3 and 4. Following cycle 4, pts underwent stem cell mobilization and could then proceed with either autologous stem cell transplant (ASCT) or defer transplant and receive four more cycles of induction therapy with elo plus len, bortez, and dex. Following either ASCT or 8 cycles of induction chemotherapy, pts transitioned to risk-adapted maintenance with elo, len, and dex plus every other week bortez (pts with high-risk cytogenetics, ISS stage II or III) or elo, len, dex (all others). Responses were assessed by the modified Uniform Response Criteria and toxicities graded based on NCI-CTCAE V4. Results: 41 patients with a median age of 60 were enrolled and this analysis encompasses response data from 29 patients. The overall response rate (ORR) after four cycles was 100%, with 24% achieving a complete response (CR), 47% achieving a very good partial response (VGPR), and 29% a partial response (PR). The rate of VGPR or better was 71%. The median number of CD34+ stem cells collected was 10.3 x 10^6. The most frequent grade 3 or higher toxicities included thrombocytopenia (15%) and hypophosphatemia (12%). The rate of grade 3 or higher peripheral neuropathy was 2%. Two pts died while on study, one due to complications of septicemia and the other due to respiratory failure. Conclusions: The combination of elo plus len, bortez, and dex was effective in newly diagnosed, ASCT-eligible patients. The rate of high-grade toxicities was low, although there were two grade 5 events (septicemia and respiratory failure). Clinical trial information: NCT02375555.
Natural history of t(11;14) multiple myeloma (MM).
Authors: Lakshman Arjun , Alhaj Moustafa Muhamad , Rajkumar S.Vincent , Dispenzieri Angela , Gertz Morie A. , Buadi Francis , Lacy Martha , Dingli David , Hayman Suzanne R. , Gonsalves Wilson I. , Kapoor Prashant , Leung Nelson , Lin Yi , Go Ronald S. , Kourelis Taxiarchis , Lust John Anthony , Russell Stephen , Zeldenrust Steven R. , Kyle Robert A. , Kumar Shaji 
Published: September 2018

8014 Background: t(11;14) is a standard risk cytogenetic marker in MM. Methods: We reviewed 366 patients with MM who had t(11;14) by FISH and 732 age and period-matched controls without t(11;14), seen at our institution from 2004 to 2014 and outcomes were analyzed using time to first progression or death (PFS1) and overall survival (OS). Results: For the t(11;14) group at diagnosis, the median age was 63.7 yr (range, 22.1-95.4) with 64.5% of patients being male. Eighty nine (24.3%) patients were above 70 yr of age at diagnosis. 33.8%, 40.3% and 25.9% patients belonged to ISS 1, II and III stages respectively. 13% patients had elevated LDH. Monosomy 17 or del 17p were identified in 10.6% patients. The median follow up period was 56.9 months (m) (95% CI: 54.6-62.2) and 209 (57.1%) patients were alive at last follow-up. Among patients receiving proteasome inhibitor (PI)-based, immunomodulator (IMiD)-based, PI+IMiD based or other agent based induction therapy, 71.2%, 70.3%, 90.4% and 37.5% patients respectively attained ≥PR as best response to induction (p < 0.01). During their course, 223 (60.9%) patients underwent stem cell transplant. Median PFS1 and OS were 23.1 (CI: 20.8-27.9) and 78.6 (CI: 66.7-105.9) m respectively. Among the controls, high risk cytogenetics (HRC) was present in 142 (19.4%), and the median OS was 83.8 m (CI: 70.8-97.0) being comparable to t(11;14) group (p = 0.8). For all 1098 patients, using a Cox-proportional hazards model with age > 70 years, induction therapy (novel agent-based vs others), cytogenetics [HRC vs t(11;14) without HRC vs no HRC or t(11;14)], and ISS stage III vs II/I as predictors, age > 70 years [HR-2.2 (CI: 1.8-2.8) and p < 0.01], ISS III vs ISS II/I [HR-1.4 (CI: 1.1-1.8) and p < 0.01] and HRC [HR of 2.1 (CI: 1.6-2.8) vs no HRC or t(11;14) (p < 0.01) and 1.9 (CI = 1.4-2.6) for t(11;14) without HRC (p < 0.01)were associated with reduced OS. The risk for reduced OS did not differ between t(11;14) without HRC, and those without t(11;14) or HRC [HR-1.1 (CI: 0.9-1.4), p = 0.4]. Conclusions: Our study characterizes the outcomes of a large cohort of MM patients with t(11;14) at diagnosis. Advanced age, HRC and advanced stage at diagnosis were associated with worse OS in our cohort. t(11;14) MM without HRC does not differ in outcome compared to non-t(11;14) MM without HRC.
Pembrolizumab (Pembro) plus lenalidomide (Len) and low-dose dexamethasone (Dex) for relapsed/refractory multiple myeloma (RRMM): Efficacy and biomarker analyses.
Authors: Ocio Enrique M. , Mateos Maria-Victoria , Orlowski Robert Z. , Siegel David , Reece Donna Ellen , Moreau Philippe , Rodriguez-Otero Paula , Munshi Nikhil C. , Avigan David , Ghori Razi , Wnek Richard , Mogg Robin , Marinello Patricia Maria , San Miguel Jesus 
Published: September 2018

8015 Background: The PD-1 inhibitor pembro blocks interaction of PD-1 with its ligands PD-L1/PD-L2, activating antitumor immunity. Combination of pembro, len, and dex may provide synergistic antitumor activity in RRMM. Methods: Theopen-label, phase 1 KEYNOTE-023 (NCT02036502) study of pembro + len + low-dose dex enrolled patients (pts) with RRMM treated with ≥2 prior therapies (tx). Pts received pembro 200 mg IV Q2W, len 25 mg PO on d1-21, and dex 40 mg PO weekly on each 28-d cycle. Primary end point was safety. ORR was assessed by IMWG 2006. Exploratory biomarker analyses included flow cytometry (FC) (PD-L1, PD-L2 on CD38+CD138+ cells) at screening or predose cycle 1, d 1 bone marrow (BM) aspirate. Absolute and/or relative numbers of circulating immune cells (by FC) and gene expression profile (GEP) (by Nanostring) were evaluated in predose cycle 1, d1 and cycle 2, d1 blood. Results: Median age was 61 y; median (range) prior lines of tx was 4 (1-10); 38 (75%) pts were len-refractory and 27 (53%) pts were double refractory. Most common grade ≥3 tx-related AEs (TRAEs) were neutropenia (33%), thrombocytopenia (18%), and anemia (12%). 2 (4%) pts died (hepatic failure, ischemic stroke) because of TRAEs. Immune-related AEs occurred in 5 (10%) pts. No pneumonitis was reported. For response-evaluable pts, ORR was 50% (20/40; 1 sCR, 14 PR, 5 VGPR); 1 had PD. ORR was 38% (11/29) for len-refractory pts. In 16/32 pts with FC-evaluable BM aspirate with >100 CD38+CD138+ cells, all were PD-L1+, while PD-L2 expression was variable. At cycle 2, d1, frequency of circulating HLA-DR+, central (CD45RO+CCR7-), and effector memory (CD45O+CCR7+) CD8+ T cells significantly increased and naive (CD45RA+) CD8+ T cells significantly decreased; all with multiplicity adjusted P values ≤ 0.01. Conclusions: Pembro + len + low-dose dex has an acceptable safety profile and antitumor activity in pts with RRMM, including len-refractory pts. PD-L1 was expressed in all pts evaluated by FC, whereas PD-L2 expression was variable. Among the pool of circulating T cells in peripheral blood, HLA-DR+ and memory T-cell subset fractions increased after treatment. Clinical trial information: NCT02036502.
Autologous stem cell transplant (ASCT) for newly diagnosed multiple myeloma (MM) in the era of novel agents: A meta-analysis of phase III randomized controlled trials.
Authors: Dhakal Binod , Chhabra Saurabh , Hamadani Mehdi , D'souza Anita , Usmani Saad Zafar , Jackson Jeffrey , Hari Parameswaran 
Published: September 2018

8022 Background: Given the unprecedented deep response rates with the novel agent induction, the role of high dose therapy (HDT) followed by ASCT in MM pts. has been questioned, and was re-evaluated in a number of randomized clinical trials (RCTs). Although, the results of most studies suggest the continued benefit of HDT/ASCT, some RCTs suggest no overall survival (OS) benefit. We undertook a systematic review and meta-analysis of phase III randomized RCTs evaluating the role of HDT compared to standard therapy (SDT) in the context of novel agent induction Methods: We searched the PubMed, Scopus and Cochrane Collection of Controlled Trial databases using the term myeloma combined with autologous or transplant or myeloablative or stem cell from 2000-2016. A total of 2480 articles identified, of which 4 large phase III RCTs compared upfront HDT with SDT with novel agents use. Two individuals independently extracted the data. Reported hazard ratio (HR) and survival data were pooled using random effects models (STATA v14, College Station, Tx). Heterogeneity was assessed using I2. Results: Four studies comprising 2421 patients were included (Table 1). One study did not report the HR for death and hence OS analysis was limited to 3 studies. The combined hazard for progression with HDT was 0.55 (95% CI 0.40-0.71) (p < 0.005). The combined hazard for death with HDT was 0.65 (95% CI 0.29-1.0) (p = 0.007). Sensitivity and sub-group analysis showed no difference in PFS (p = 0.06) and OS (p = 0.22) with HDT. Significant heterogeneity was demonstrated by I2 of 71.4% for PFS (p = 0.01) and 68.4% for OS (p = 0.04). Conclusions: Based on our analysis, even in the novel agent era, HDT appears to be beneficial and should be considered standard of care for all transplant eligible MM pts. [Table: see text]
Impact of t(11;14) on outcomes in African American (AA) and non-AA (NAA) patients (Pts) with newly diagnosed multiple myeloma (NDMM): Connect MM registry.
Authors: Gasparetto Cristina , Abonour Rafat , Jagannath Sundar , Durie Brian G. , Shah Jatin J. , Narang Mohit , Terebelo Howard R. , Toomey Kathleen , Hardin James , Wagner Lynne I. , Srinivasan Shankar , Kitali Amani , Flick E. Dawn , Zafar Faiza , Agarwal Amit , Rifkin Robert M. 
Published: September 2018

8023 Background: t(11;14) is a common cytogenetic abnormality historically associated with standard-risk and generally favorable MM outcomes, but has shown poor prognosis in some retrospective analyses. Connect MM is a prospective, US, observational, multicenter registry that collects data on management and natural history of NDMM pts in clinical practice. The impact of t(11;14) on survival outcomes was assessed in AA and NAA pts. Methods: Adult NDMM pts who completed induction and were tested for t(11;14) by FISH/cytogenetics were grouped by race (AA vs NAA). Endpoints were PFS and OS. Kaplan-Meier analyses were adjusted for differences in cohort, age, ISS stage, transplant intent, t(4;14), hemoglobin, platelets, calcium, creatinine, and diabetes history. Data cutoff was Jul 7, 2016. Results: 3011 pts were enrolled in 2 cohorts (Cohort 1: n = 1493, Sep 2009–Dec 2011, median follow-up = 39.3 mos; Cohort 2: n = 1518, Dec 2012–Apr 2016, median follow-up = 16.4 mos). Of 1539 (52%) pts tested for t(11;14), 363 (24%) were t(11;14)-positive, including 53 (26%) of 205 AA and 310 (23%) of 1334 NAA pts. First-line bortezomib exposure was similar across groups. A trend of shorter PFS was observed in AA pts with t(11;14) vs AA without t(11;14) (Table). AA pts with t(11;14) had significantly higher risk of death compared to those without t(11;14) and higher rate of early mortality than NAA pts. No differences in PFS or OS were noted in NAA pts with or without t(11;14). For OS, the interaction between race and t(11;14) status was statistically significant ( P= 0.004). Conclusions: In Connect MM, the effect of t(11;14) on OS was significantly different between AA and NAA pts. t(11;14) was associated with poorer survival outcomes in AA pts, and thus, may be a risk factor for poor prognosis. Additional analyses will be conducted to elucidate the role of induction treatment, transplant and maintenance in AA and non-AA pts with t(11;14). Clinical trial information: NCT01081028. [Table: see text]
MOR202 with low-dose dexamethasone (Dex) and in combination with pomalidomide/dex and lenalidomide/dex in relapsed or refractory multiple myeloma (RRMM): Interim analysis of a phase I/IIa dose-escalation study.
Authors: Raab Marc , Chatterjee Manik , Goldschmidt Hartmut , Agis Hermine , Blau Igor W. , Einsele Hermann , Engelhardt Monika Martha , Ferstl Barbara , Gramatzki Martin , Röllig Christoph , Weisel Katja C. , Jarutat Tiantom , Weinelt Dominika , Winderlich Mark , Boxhammer Rainer , Peschel Christian 
Published: September 2018

8024 Background: CD38 is a type II transmembrane glycoprotein expressed by MM cells. MOR202, a human IgG1 CD38 monoclonal antibody, has shown high single-agent activity in preclinical models of MM and synergy in combination with immunomodulatory drugs (IMiDs), lenalidomide (LEN) and pomalidomide (POM). Methods: This interim analysis of a multicenter phase I/IIa study reports safety and efficacy data from RRMM patient (pt) cohorts treated with clinically relevant doses of MOR202 (2-hour IV infusion; 4, 8 and 16 mg/kg q1w) + Dex (≤40 mg), or at 8 or 16 mg/kg q1w with an IMiD/Dex. Primary objectives were to evaluate the safety, maximum tolerated dose (MTD) and recommended phase II dose of MOR202. Results: As of January 2017, 79 pts had been treated, including 44 in clinically relevant cohorts: 18 received MOR202 + Dex, 15 MOR202 + LEN/Dex and 11 MOR202 + POM/Dex. Pts had received a median of 3, 2 and 3 prior treatment lines, respectively. The MTD of MOR202 was not reached. Combinations were generally well tolerated, with grade ≥3 adverse events (AEs) mainly hematological; 2 pts discontinued due to a MOR202-related AE (one grade 4 thrombocytopenia; one grade 3 acute kidney failure). Infusion-related reactions (all grade 1 or 2) were seen in only 3/44 (7%) pts, and mainly occurred during the first infusion. In the MOR202 + Dex cohort, 5/17 (29%) evaluable pts (receiving at least 1 cycle of treatment) had a response, including 3 with partial responses (PRs) and 2 with very good PRs (VGPRs). Responses were also seen in 11/13 (85%, 8 PRs, 3 VGPRs) evaluable pts in the MOR202 + LEN/Dex cohort and 5/9 (56%, 2 complete responses, 3 PRs) in the MOR202 + POM/Dex cohort. Longest response duration was 17 months (MOR202/Dex). Preliminary analysis showed preservation of high CD38 levels on MM cells under MOR202 therapy. Conclusions: In heavily pretreated pts with RRMM, a 2-hour infusion of MOR202 administered at up to 16 mg/kg with Dex or in combination with an IMiD/Dex, showed a favorable safety profile, including excellent infusion tolerability. Promising preliminary efficacy and long-lasting tumor control was seen. Clinical trial information: NCT01421186.
Factors predicting organ response in light chain amyloidosis (AL).
Authors: Sidana Surbhi , Tandon Nidhi , Dispenzieri Angela , Gertz Morie A. , Buadi Francis , Lacy Martha , Dingli David , Fonder Amie L. , Hayman Suzanne R. , Hobbs Miriam A. , Gonsalves Wilson I. , Hwa Yi Lisa , Kapoor Prashant , Kyle Robert A. , Leung Nelson , Go Ronald S. , Lust John Anthony , Russell Stephen J. , Rajkumar S. Vincent , Kumar Shaji 
Published: September 2018

8048 Background: Organ response (OR) in AL is often delayed and difficult to predict early. Methods: We retrospectively analyzed 1308 patients (pts) with newly diagnosed AL from 2006 – 2015 to determine factors which could predict for OR. Results: Median age was 64 years (yr) and Mayo Stage was: 1 (22%); 2 (23%); 3 (25%); 4 (31%). Organ involvement was: cardiac (74%, n=932); renal (59%, n=738), liver (16%, n=205); gut (24%, n=310) and autonomic (12%, n=152). 59% (n=765) had > 1 organ involved, including 43% (n=567) with > 1 critical organ (heart, kidney, liver) involved. Treatment was: ASCT based (28%, n=330, N=1186), bortezomib based (24%, n=281), alkylator based (33%, n=392), others (5%, n=54) and none (10%). In evaluable pts, VGPR or better rates were: 53% at 6 months (m) (N=625), 72% at 12 m (N=465) and 57% overall (N=688). Table 1 lists OR at various time points. Complete OR in all involved critical organs was seen in: 51% (n=308, N=600), partial response (at least 1 OR when >1 organ involved) in 12% (n=73) and none in 37% (n=219). Complete OR was associated with better overall survival (OS) than partial or no OR (median OS: not reached vs 42 m vs 29 m; P <0.0001). In multivariate model the following variables at baseline or 1 yr mark were predictive of complete OR: lower Mayo Stage (p=0.01), fewer critical organs involved (p=0.007), higher baseline GFR (p=0.03), female sex (Complete OR 60% vs 47%; p=0.04) and VGPR at 1 yr (Complete OR 70% vs. 36%; p <0.0001). Other factors included in the model were age (p=0.9), bilirubin (p=0.1) and transplant (p=0.2). All aforementioned factors were significant in univariate analysis. Conclusions: Achievement of response in all involved critical organs is associated with better survival in AL pts than partial or no OR. Various baseline factors and VGPR at 1 yr can predict for achieving complete OR, with 70% pts who achieve VGPR at 1 yr having a complete OR. [Table: see text]
Salvage guideline for local-regional failure after stereotactic ablative radiotherapy for early-stage non-small cell lung cancer.
Authors: Brooks Eric , Sun Bing , Zhao Lina , Komaki Ritsuko , Liao Zhongxing X. , Jeter Melenda , O'Reilly Michael , Welsh James William , Gomez Daniel Richard , Nguyen Quynh , Antonoff Mara , Hahn Stephen M. , Heymach John , Rice David C. , Chang Joe Y. 
Published: September 2018

8501 Background: Up to 1 in 7 patients receiving stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer (NSCLC) will develop local-regional recurrence. While SABR is the pillar of treatment for medically inoperable patients, little is known about outcomes and management for this potentially curable, local-regionally recurrent patient group. Methods: We present the first long-term results for the largest group of salvaged patients with local-regional recurrence after SABR. 772 patients with clinically early-stage I-II NSCLC were treated with SABR (50 Gy in 4 or 70 Gy in 10 fractions) between 2004-2014 at our center. Patients with isolated local recurrence (LR, n = 34) or regional recurrence (RR, n = 41) were analyzed and compared to patients with no recurrence (NR, n = 569). Results: Median time to LR or RR after SABR was 14 months. Salvage was performed in 79.4% of LR and 92.7% of RR patients. Salvage consisted of surgery (20% LR, 2% RR), re-irradiation (24% LR, 17% RR), radiofrequency ablation (15% LR), chemotherapy (15% LR, 26% RR), and chemoradiation (6% LR, 44% RR) based on a standard multi-disciplinary decision approach (Figure 1). 5-year OS was 37.1% for LR and 39.1% for RR patients. Of LR and RR patients, those receiving salvage had significantly better 5-year OS compared to those not receiving salvage (45.2% LR, 42.9% RR, 0% no salvage; p = 0.009). 5-year OS for salvaged patients was not statistically different from patients with NR (53.5% NR, p = 0.466). 5-year lung-cancer specific survival was 51% for LR and 55.1% for RR patients. Subsequent DM occurred in 20.5% of LR and 29.3% of RR patients at a median of 8.4-10.3 months. No salvaged patient experienced grade 5 toxicity. Conclusions: Patients with local or regional recurrence after SABR have excellent outcomes with salvage therapy, with no statistical difference in 5- year OS between LR and RR patients salvaged after SABR, and patients with no recurrence. Because a standard multidisciplinary approach was applied to any LR or RR patient after SABR, a novel treatment algorithm is generated. We offer a much needed management guide for thoracic oncologists treating patients who local-regionally recur after SABR.