bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy, safety, tolerability and price of newly approved drugs in solid tumors.
Authors: Barnes Tristan Alexandra , Amir Eitan , Templeton Arnoud J. , Gomez Garcia Susana , Navarro Beatriz , Seruga Bostjan , Ocana Alberto 
Published: September 2018

e18336 Background: New anti-cancer drugs utilize diverse mechanisms of action. Here we evaluate their differential efficacy, safety, tolerability and price. Methods: Drugs approved for the treatment of solid tumors between 2000 and 2015 were identified and analyzed in subgroups: agents targeting oncogenes or dysregulated pathways (group 1), anti-angiogenic drugs (group 2), immunotherapy (group 3), and chemotherapy (group 4). Hazard ratios (HRs) were extracted from the reports of randomized trials supporting registration and pooled in a meta-analysis. Odds ratios (ORs) for rates of toxic death, treatment discontinuation and grade 3-4 toxicity were compared relative to control groups. The Micromedex Red Book was used to calculate the monthly price of each agent. Results: Analysis included 74 studies comprising 48,527 patients. Progression-free survival (PFS) was improved to a lesser degree with groups 3 and 4 than with groups 1 and 2, (pooled HR:0.54, 0.56, 0.63, and 0.76 for groups 1–4 respectively, p for difference < 0.001). Compared to PFS, there was a lower magnitude of improvement overall survival in all groups and the degree of benefit was less for group 4 than for other groups (pooled HR:0.77, 0.78, 0.68, and 0.83 for groups 1–4 respectively, p for difference = 0.007). Compared to control groups in individual trials, immunotherapy was associated with better safety and tolerability than other groups. Drug prices have increased over time with no statistically significant difference between groups. There was limited to no correlation between drug pricing and efficacy. Conclusions: Compared to control groups, chemotherapy improves efficacy to a lesser degree than the other groups. Immunotherapy appears to have better safety and tolerability profile compared to other cancer therapies. Market price of drugs is not related to efficacy.
Association of pre-allogeneic hematopoietic stem cell transplant 25-hydroxy-vitamin D level and development of acute skin graft-versus-host-disease: A retrospective analysis of 154 patients.
Authors: Joseph Ranjit , Jabbar Seema , Reddy Manasa , Houghton Damon Eugene , Yun Trull , Tan Xainming , Hashim Ibrahim 
Published: September 2018

e18539 Background: The pathophysiology of acute skin graft versus host disease (asGVHD) is thought to be initiated when donor T cells encounter recipient dendritic cells (DC) and become activated. Studies have shown that vitamin D (VD) inhibits DC maturation, polarizes T cell populations toward Th2 cytokine phenotype, And biases toward tolerating T cell populations. We analyzed pre-SCT serum vitamin D levels and sought to determine an association with development of acute skin GVHD. Methods: 154 patients, with matched SCT at UTSW Medical Center from December 2007 to December 2014, and who had serum samples banked prior to conditioning were included in the analysis. Pertinent data were extracted from the UTSW BMT database and EMR. Serum samples collected 1-3 months prior to SCT were used to detect 25-hydroxyvitamin D (VD) concentrations. Cumulative incidence (CI) of asGVHD grade II-IV were assessed within 100 days post-SCT. A significantl difference (p-value = 0.026, Breslow-Day test) in the associations between Vit D and asGVHD for patients under RIC and ABLgroups was present, so we analyzed the primary endpoint, time to asGVHD since SCT, separately among two these 2 groups. CI functions were constructed with death and relapse as competing risks. Results: Out of 154 patients, 93 were male, mean age was 51, range 20-72 and median VD was 21 ng/ml (range 7.1-63.3). There were 112 patients with VD < 25 ng/mL (VD < 25) and 41 with VD ≥ 25 ng/mL (VD≥25). Age, conditioning regimen, donor type, cell source, ABO compatibility, GVHD prophylaxis were similar in both groups. Overall CI asGVHD was 24%. CI of asGVHD was 23.8% in VD≥25 and 24.1% in VD < 25. Patients were then analyzed separately with respect to type of conditioning regimen they received (Ablative (ABL) vs Reducing intensity (RIC)). Figure 1A shows that in the ABL group the CI of asGVHD appears increased in patient with VitD≥25 (40% vs 27.1%, p = 0.27). In contrast, Figure 1B shows that in RIC group the CI of asGVHD is higher for those with VD < 25 (4.8% vs 24.1% , p = 0.05). Conclusions: After accounting for competing factors, KM analysis in the RIC group showed that patients with VD level < 25 ng/mL were at a higher risk of developing asGVHD. Further studies to clarify the association between VD status and development of asGVHD are warranted.
Survival outcomes in patients with chronic phase chronic myeloid leukemia (CP-CML) receiving third- or subsequent line (3L) treatment prior to the availability of ponatinib.
Authors: Stellato Daniel R , McGarry Lisa , Huang Hui , Hastings Shaina , Delea Thomas E. 
Published: September 2018

e18553 Background: PACE was a phase 2 single-arm trial of ponatinib, a 3rd-generation tyrosine kinase inhibitor (TKI), in 449 highly-refractory patients with CML or Philadelphia-chromosome positive (Ph+) acute lymphocytic leukemia (ALL) or who had the BCR-ABL T315I mutation. Overall survival (OS) for 3L CP-CML patients in PACE at 1, 2, 3 and 4 years was estimated to be 91%, 83%, 80%, and 79%, respectively. Expected survival for 3L CP-CML patients prior to the availability of ponatinib has not been documented. Methods: A systematic literature review was conducted to estimate OS in patients with CP-CML receiving 3L treatment prior to ponatinib. Studies were identified from a review by Lipton et al. (2015), updated with studies identified from searches of electronic databases (MEDLINE, EMBASE, Cochrane Libraries) and abstract databases of key conferences. Landmark and median survival were extracted from study reports. Pseudo-individual patient data (IPD) for survival outcomes were derived from digitized Kaplan-Meier (KM) survival curves then pooled and analyzed using KM methods. Results: Fifteen studies (717 patients) were identified that reported median, landmark, or KM curves for survival outcomes for CP-CML patients receiving 3L treatment without ponatinib. KM curves for OS were obtained for 6 arms (3 nilotinib and/or dasatinib; 3 other TKIs). OS at 1, 2 and 3 years based on the pooled IPD is reported in the Table. To avoid confounding of OS from post-progression treatment with ponatinib, 1 study was excluded that included follow-up after the date of ponatinib’s approval. Conclusions: EstimatedOS in patients with CP-CML receiving 3L treatment prior to ponatinib appears to be shorter than that observed among ponatinib-treated patients in PACE: 4-year survival probability in PACE is higher than estimated 2-year survival probability prior to ponatinib. Further analyses are needed to identify and adjust for potentially confounding factors. [Table: see text]
Treatment of essential thrombocytopenia patients intolerant/ resistant to hydroxyurea: A physician survey.
Authors: Nejadnik Bijan , Mascarenhas John , Rappaport Karen M , Lu Biao , Gagnon Bruno M , Verstovsek Srdan 
Published: September 2018

e18565 Introduction: Hydroxyurea (HU) is deemed first-line cytoreductive therapy for patients with essential thrombocythemia (ET) at high-risk for vascular complications with 20-25% of patients developing HU intolerance/ resistance (HUIR). Up to one-third of patients taking anagrelide, often the 2nd line drug of choice, are also unable to tolerate its side effects (cardiovascular and gastrointestinal). A review of the medical literature suggests widespread support for individualized treatment plans in ET with multiple options, including HU, anagrelide, interferon and busulfan, but little is known about physician practice. Methods: We contracted with a research company to perform an internet survey of 20 academic and 20 community hematologists to assess treatment practices for HUIR ET patients. We assumed a 25% rate of resistance to anagrelide. Results: Academic and community physicians reported 22% and 25% HUIR rates, respectively. An estimated 60% and 44% of HUIR patients in academic and community settings, respectively, would undergo treatment with an agent other than anagrelide (interferon, busulfan, or ruxolitinib) in 2nd or 3rd line treatments. Physicians not using anagrelide as 2nd line therapy also would not use it as 3rdline therapy. Anagrelide is used more frequently in the community setting. Conclusions: About 50% of HUIR patients are treated with agents other than anagrelide as 2nd/ 3rdline therapy. Reasons for practice variation in the treatment of ET remain poorly understood. [Table: see text]
Evidence of low incidence of myelodysplastic syndrome (MDS) in patients exposed to bendamustine treatment for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Authors: Burke John M. , Bibeau Kristen , Kahl Brad , Carson Kenneth R. , Zelenetz Andrew D. , Brander Danielle M. , Maddocks Kami J. , Gerecitano John F. , Pathak Ashutosh K. , Cheson Bruce D. 
Published: September 2018

e19008 Background: CLL/SLL is a treatable malignancy, which is responsive to therapies that include bendamustine. However, as with many alkylating agents, there is concern for the development of secondary malignancies and MDS after exposure to bendamustine. We evaluated the risk of MDS using electronic medical records from a geographically diverse cohort of cancer patients (pts). Methods: Pathologically confirmedCLL/SLL pts with any exposure to bendamustine were identified in the Flatiron Health database (FHD, Flatiron Health, New York [122016]). This is a longitudinal US-based cohort with > 1.5 million cancer pts drawn from over 250 cancer clinics. Pts with bendamustine exposure and no history of MDS or other malignancy were included. Pts were followed longitudinally to identify incident cases of secondary malignancies or MDS. Results: Of 3140 CLL/SLL pts in the analytic cohort, 1022 met inclusion criteria. Median follow-up after bendamustine exposure was 1.7 years. Overall, 8% received bendamustine monotherapy, 84% received combination therapy, and 8% received cycles of bendamustine monotherapy and combination therapy. Of the 1022 pts, 205 (20%) had prior antineoplastic exposure, a risk factor for MDS. During the follow-up period, five pts developed MDS (0.48% of the bendamustine-exposed cohort), one of whom had prior antineoplastic exposure. Conclusions: This real-world study demonstrated that pts received bendamustine overwhelmingly as combination therapy, and 20% had prior antineoplastic exposure. MDS related to alkylators and purine analogs can have a latency of > 3 years; in this study a minority (~20%) of pts had > 3 years of follow-up. Thus, longer follow-up is required to draw definitive conclusions regarding the risk. Nevertheless, the FHD provides a source of oncology data for studying long-term outcomes of cancer pts, which have historically been difficult to capture in epidemiological studies. At a median of 1.7 years after exposure, the current study identified a low risk of MDS after controlling for potential confounders.
Clinical outcomes of DLBCL, follicular lymphoma (FL) and Richter transformation (RT) patients treated with ibrutinib: A real-world experience of off-label ibrutinib use.
Authors: Isaac Krista , Kennard Kaitlin , Landsburg Daniel Jeffrey , Hughes Mitchell E. , Svoboda Jakub , Nasta Sunita , Latorre Tanya , Surkis William , Fanning Molly J , Chatburn Elizabeth , Dorsey Colleen , Daniel Catherine , Timlin Colleen , Gill Jennifer , Schuster Stephen J. , Mato Anthony R. 
Published: September 2018

e19043 Background: Ibrutinib (IBR), a BTK inhibitor, is FDA approved for CLL, Waldenstrom macroglobulinemia, marginal zone lymphoma and mantle cell lymphoma. Despite limited data, IBR is being utilized as a therapy for patients (pts) with relapsed/refractory (RR) DLBCL and FL. In an effort to further characterize the efficacy of IBR in these settings, we conducted a retrospective cohort study of IBR-treated pts with DLBCL, RT or FL. Methods: A retrospective cohort study of DLBCL, RT and FL pts treated with IBR was completed. Data collected included demographics, stage, IPI, prior treatments, IBR dose/duration, reasons for discontinuation, and response. PFS and OS were estimated using the Kaplan Meier method. Results: 44 pts were identified (DLBCL: n = 24, 55%; FL: n = 12, 27%; RT: n = 8, 18%). Baseline characteristics: age (range 19 – 80), 61% male, 95% ECOG 0 - 1, 71% stage IV, 62% elevated LDH, 48% R-IPI ≥ 4. DLBCL subtypes (Hans criteria) were 46% non-GC (n = 11), 29% GC (n = 7), 25% unclassifiable (n = 6). In FL, 8% were grade 1, 59% grade 2, and 33% grade 3a. Med number of prior therapies was 5 (range 1-11). Most common reasons for IBR discontinuation were progression (35%), toxicity (20%), bridge to CAR-T (10%). PFS and OS data are shown in the table below. In DLBCL, cell of origin (Hans) did not impact outcomes (p = .97, LR test). PFS was superior in RT as compared to DLBCL (p = .03, LR test). Conclusions: In the largest single-center, real-world experience of IBR use in DLBCL, RT and FL, we validate findings reported in clinical trials. In FL, responses appear to be durable (median PFS > 10 months). Outcomes are poor in DLBCL and use of IBR as monotherapy is not recommended. Perhaps IBR is best used as a short-term bridge to more definitive therapies. Cell of origin (Hans) may not predict PFS and should not be used to select pts for IBR. Pts with RT appear to have more durable responses (vs. DLBCL) suggesting differing dependence on BTK signaling. [Table: see text]
Differences in health care costs and utilization: BR vs RCHOP in patients with follicular lymphoma.
Authors: Zhou Jifang , Pathak Ashutosh K. , Brander Danielle M. , Gabriel Susan 
Published: September 2018

e19049 Background: Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma (iNHL) with an incidence of more than 1500 cases annually and comprising 35% of all iNHL cases in North America. Combination chemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) or bendamustine plus rituximab (BR) are both category 1–approved first-line therapies. This analysis examined differences in healthcare costs and utilization between two cohorts of newly diagnosed FL patients undergoing BR or RCHOP therapy. Methods: Newly diagnosed FL patients from 1/1/2006 to 7/31/2016 treated with first-line RCHOP or BR were identified in the Truven Health MarketScan Research Databases. Inclusion criteria were age ≥18 years and continuous enrollment from 3 months before to 1 month after the index date (eg, first prescription for RCHOP/BR). Healthcare utilization and costs were calculated on a per month basis from the index date to 6 months post-index date. Costs included all payments made by insurance providers except for pharmacy claims. Healthcare utilization variables included number of outpatient visits, emergency room (ER) visits (yes/no), and hospitalizations (yes/no). Logistic regression and general linear models were used to test for differences. Results: Of the 6460 FL patients (male = 55%; mean age = 60.46 years, SD = 12.56) identified, 2360 were in the BR cohort and 4100 patients were in the RCHOP cohort. At baseline, the BR cohort was significantly older; had more comorbid conditions, lower costs, and fewer outpatient visits; and was less likely to have an ER visit or hospitalization relative to RCHOP patients. Over the first 6 months of therapy, controlling for baseline differences, the BR group experienced significantly lower costs and fewer outpatient visits. The BR cohort was also significantly less likely to be admitted to the ER or experience a hospitalization. Conclusions: The results of this analysis suggest that, in general, the healthcare costs and utilization of FL patients receiving BR is significantly lower than for RCHOP patients. These results support the emerging prominence of BR as an effective and safe first-line treatment option for FL patients.
Fluoroquinolone prophylaxis for the prevention of central line-associated bloodstream infection in autologous stem cell transplant.
Authors: Ziegler Matthew , Gilmar Cheryl , Landsburg Daniel Jeffrey , Pegues David , Kucharczuk Colleen , Gorman Theresa , Bink Kristen , Moore Amy , Fitzpatrick Rebecca , Stadtmauer Edward A. , Mangan Patricia , Kraus Kelly , Han Jennifer 
Published: September 2018

e19508 Background: Patients (Pts) undergoing stem cell transplant (SCT) for the treatment of hematologic malignancy are at increased risk for central line-associated bloodstream infection (CLABSI). Use of prophylactic antibiotics to prevent CLABSI in autologous SCT (autoSCT) is of unclear benefit. We aimed to evaluate the impact of levofloxacin prophylaxis on reducing CLABSI in autoSCT. Methods: Pts undergoing autoSCT at the University of Pennsylvania received levofloxacin prophylaxis during a 6-month intervention period from 1/13/2016 - 7/12/2016. Levofloxacin was administered from autoSCT until day 13, absolute neutrophil count > 500/mm3, or febrile neutropenia. Outcomes were compared to a retrospective cohort who underwent autoSCT, but did not receive routine antibacterial prophylaxis during the previous year (1/13/2015 – 1/12/2016). The primary endpoint was incidence of CLABSI assessed using Cox proportional hazards regression. Results: A total of 243 pts underwent autoSCT, with 69 receiving levofloxacin prophylaxis during the intervention period. Median age was 59 yrs, 74% had multiple myeloma, and 58% received melphalan 200mg/m2. Median duration of neutropenia was 6 days. CLABSI rate was reduced from 18.4% during the baseline period to 7.3% during the intervention period ( P= 0.03). There were no significant differences in characteristics between the baseline and intervention groups except for liver disease (1% versus 5%, P= 0.03). On multivariable analysis, levofloxacin prophylaxis was associated with a significant reduction in CLABSI incidence (HR 0.33; 95% CI 0.12-0.88; P= 0.02), as was underlying multiple myeloma (HR 0.38; 95% CI 0.20-0.74; P= 0.004) and liver disease (HR 4.31; 95% CI 0.99-18.8; P= 0.05). There was also a reduction in neutropenic (NTP) fever (OR 0.21; 95% CI 0.11-0.38; P< 0.001) and a trend toward reduction in ICU transfer for sepsis (OR 0.13; 95% CI 0.01-1.39; P= 0.08) in patients receiving levofloxacin prophylaxis. There were no significant differences in rates of secondary BSIs, C. difficileinfection, or mortality. Conclusions: Levofloxacin prophylaxis was effective in reducing CLABSI and NTP fever in patients undergoing autoSCT.
The use of proteasome inhibitors among patients with POEMS syndrome.
Authors: Kourelis Taxiarchis , Kapoor Prashant , Dingli David , Stewart A. Keith , Buadi Francis , Gertz Morie A. , Lacy Martha , Kumar Shaji , Gonsalves Wilson I. , Go Ronald S. , Lust John Anthony , Hayman Suzanne R. , Warsame Rahma M. , Rajkumar S.Vincent , Zeldenrust Steven R. , Russell Stephen J. , Hwa Lisa , Kyle Robert A. , Dispenzieri Angela 
Published: September 2018

e19530 Background: Neuropathy is a universal symptom of patients with POEMS syndrome, which makes the use of bortezomib less appealing. However, proteasome inhibitors (PIs) can provide rapid and deep hematologic responses in plasma cell disorders. Because there is very little data regarding the use PIs in POEMS syndrome, we performed a study of patients with POEMS syndrome treated with PIs. Methods: Among the 167 patients with POEMS syndrome seen at our institution between 2001-2016, we identified 12 patients who received a PI. One patient receiving < 1 cycle of bortezomib because of worsening neuropathy was included but was excluded from response analyses. One patient received 2 different PIs at separate points during the disease course and each course was considered separately. Four response categories were considered: hematologic, PET, VEGF and clinical as previously described (Dispenzieri et. al AJH 2015). Results: Among the 12 patients who received 13 courses of therapy, the median age at PI initiation was 59; 8 patients were male. Median number of prior therapies was 1 (0-4) and median time from diagnosis to initiation of PI was 75 months. Excluding steroids, regimens were as follows: bortezomib, n=3; bortezomib and cyclophosphamide, n=4; carfilzomib, n=1; and ixazomib, n=1. With a median follow-up from PI initiation of 18 months, the median duration of treatment was 7 months (1-18). Three patients achieved a hematologic CR. Of 6 patients with an abnormal baseline VEGF, 3 achieved normalization VEGF levels. Of 5 patients with an abnormal baseline PET, 2 achieved normalization of their PET. Two patients had improvement of their neuropathy, with the rest having stable symptoms. Of 9 patients with fluid overload, 8 improved. Only 2 patients stopped therapy due to worsening neuropathy related to PIs. Median PFS and OS from initiation of PI were 50 months and 53 months, respectively. Conclusions: We show that PI use in patients with POEMS syndrome can be safe and effective. Nearly 75% of patients treated with bortezomib had no exacerbation of their neuropathy. Clinical improvement in severe fluid overload symptoms (edema, ascites, pleural effusions) is almost universal, making PI-based therapy an attractive potential option in these patients.
Three-year survival after combined treatment with induction chemoimmunotherapy in patients (pts) with non-small cell lung cancer (NSCLC).
Authors: Lazutin Yuriy N. , Pyltsin Sergey P. , Kharitonova Anna Pavlovna , Ayrapetova Tamara G. , Leyman Igor A. , Chubaryan Anna V. , Anistratov Pavel A. , Shogenov A. S. , Gappoeva M. A. , Afaunov M. Kh. 
Published: September 2018

e20064 Background: Induction chemotherapy (iCT) for NSCLC has potential advantages over adjuvant CT, high therapeutic compliance, the ability to influence the primary tumor and metastatic disease. Standard approaches to iCT improving are largely exhausted. However, the development of iCIT techniques using recombinant cytokines and assessment of the effectiveness of its clinical application remains poorly understood. Methods: Clinical trial included 65 pts. with stage IIB, IIIA (N2), IIIB (T4 ipsi. nod.) NSCLC, randomized in main (n = 33) and control (n = 32) groups with comparable clinical and pathological characteristics: m 23 (69.7) vs. 23 (71.8%), W 10 (30,3%) vs. 9 (28.2%); stage IIB - 8 (24.4%) vs. 9 (28.6%), IIIA - 22 (66.6%) vs. 19 (59.4%), IIIB - 3 (9%) vs. 4 (12.5%); 40-49 years 5 (15,5%) vs. 5 (15,6%), 50-59 14 (42,4%) vs.15 (46,8%), 60 years and older 14 (42,4%) vs. 12 (37,8%). Pts. of the control group received 2 iCT cycles: cisplatin 75 mg / m2 i.v. 1 day and gemcitabine 1000 mg / m2 i. v. 1 and 8 days; pts. of the main group additionally received recombinant tumor necrosis factor coupled with thymosin (TNF-T Farmaclon Russia) 50. 000 ED / m2i.v. 3, 5 and 7 days of the cycle. The direct results were evaluated 3 weeks after completion of induction. Pts. who underwent radical surgery received 2 cycles of platinum-based adjuvant CT. DFS was studied by the method of Kaplan-Meier. Results: 3-year DFS in the main group was 72% vs. 48% in the control group (p = 0.10603). Conclusions: Clinical trial of the effectiveness of iCIT with using immune drug TNF-T demonstrated a tendency to improve 3-year DFS by 24%, which favors further studies on a larger number of pts.