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Aim: Targeted therapy (TT) and immuno-oncology (IO) drugs are approved for patients with BRAF mutant metastatic melanoma (MM). We compared real-world outcomes for first-line (1L) TT versus 1L IO to evaluate optimal sequencing. Materials & methods: Physicians-identified BRAF mutant MM patients initiating 1L TT or IO therapies and extracted treatment, disease and clinical outcomes including disease response which were compared between TT and IO and individual regimens. Results: 440 MM patients (TT = 283, IO = 157) were identified. A higher proportion of TT patients had liver metastases (46.3 vs 35.0%) and abnormal lactate dehydrogenase (61.1 vs 42.7%). IO-treated had a RECIST-determined response rate of 45.9 versus 60.1% for TT and time on treatment of 7.2 versus 11.4 months, respectively. There was no survival difference between cohorts. Conclusion: Despite higher risk patients, 1L TT resulted in higher response rate and longer treatment duration suggesting a preferred 1L sequence.

Aim: To characterize real-world neurological adverse events (AEs) associated with chimeric antigen receptor T-cell therapies in patients with refractory/relapsed large B-cell lymphomas. Materials & methods: Postmarketing case reports from the US FDA AEs reporting system involving axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) for large B-cell lymphomas were analyzed. Results: Of 804 AE cases identified (637 axi-cel, 167 tisa-cel), 428 (67%) of axi-cel cases and 43 (26%) of tisa-cel cases reported neurological AEs. Compared with cases without neurological AEs, significant associations were observed between neurological AEs and use of axi-cel, age ≥65 years, and the outcome of hospitalization. Conclusion: Neurological AEs were common with chimeric antigen receptor T-cell therapy in the real world and largely reflected those reported in clinical trials.

Background: Parkinson’s disease (PD) is a progressive, neurodegenerative disease which leads to postural and gait disorders, limitation in mobility, activities of daily living and disability. Although a number of studies have shown that supervised exercise programs have short-term beneficial effects, there are few studies addressing the effectiveness of home-based physiotherapy. Therefore, this study was done to analyze the effects of home-based physiotherapy on balance in participants with Parkinson’s disease. Material and Method: From January 2018 to December 2018, 44 participants who were recipients of HealthCare at Home physiotherapy (HCAH) services across various locations were included in the main analysis. The age ranges from 63 years to 87 years (mean age 75.18 years), average treatment cycle duration was 74.2 days. Physiotherapy was performed for approximately 45-60 min aiming to improve general mobility, static and dynamic balance. Berg Balance Scale (BBS) were taken as an outcome and were recorded fortnightly. Findings: Statistically significant improvement was seen in Berg Balance score (BBS) with mean difference of 6.09. Conclusion: The results of the study shows that home- based physiotherapy interventions like stretching exercises, active assisted, active exercises, strengthening exercises, balance and gait training. were found to have a positive effect on Berg balance scores among patients with PD.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for relapsed or refractory large B-cell lymphoma (LBCL) with the Food and Drug Administration (FDA) approvals of axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel). Although the incidence of LBCL is highest among patients age ≥ 65, clinical trials supporting approval of these 2 products primarily enrolled younger patients. Safety data for axi-cel and tis-cel in older patients is limited.In this analysis, we queried the FDA Adverse Events Reporting System (FAERS) database for cases associated with axi-cel or tis-cel from the FDA approval dates for the LBCL indication for each product through December 31, 2019, and compared adverse events (AEs) reported for cases involving patients aged65 and ≥ 65.A total of 804 cases were retrieved, with 333 (41%) involving patients age ≥ 65. Cytokine release syndrome (CRS) was the most common AE reported in both age groups. Cases involving older patients had a significantly higher proportion of neurological AEs, including CAR T-cell-related encephalopathy syndrome (8% vs. 4%, p = 0.03). Some individual clinical features of CRS were significantly more common among younger age group cases, including pyrexia (33% vs. 23%, p 0.01), tachycardia (10% vs. 5%, p 0.01), and thrombocytopenia (4% vs. 2%, p = 0.03).In this age-based analysis of FAERS reports for patients treated with axi-cel or tis-cel, we identified differences in patterns of AEs experienced. This large-scale post-marketing study complements clinical trial safety data and may help inform clinicians' decision making when treating adult patients with CAR-T cell therapy.

Background: To describe healthcare costs, excluding ipilimumab drug costs, in patients with advanced melanoma receiving ipilimumab in the US community practice setting. Methods: This was a retrospective chart review of unresectable stage III/IV melanoma patients who received first-line ipilimumab monotherapy between 04/2011 and 09/2012. Healthcare resource utilization included inpatient, emergency, specialist and hospice visits, laboratory tests, radiation, surgeries, and nursing home stays. Publicly available US unit costs were applied to each resource type to estimate costs, which were analyzed by time periods: during ipilimumab treatment, post-ipilimumab treatment (post-regimen), and within 90 days prior to death (pre-death). Generalized linear mixed models were used to explore cost predictors during the treatment period, on a per-dose-interval basis, defined as the time between ipilimumab doses. Results: Data were abstracted from 273 patient charts at 34 sites. Excluding ipilimumab drug costs, total monthly costs during the treatment regimen, post-regimen, and pre-death periods were $690, $2151, and $5123, respectively. Total healthcare costs were 27 times higher during dose intervals with a grade 3/4 adverse event compared with intervals without a grade 3/4 adverse event. Eastern Cooperative Oncology Group performance status ≥ 2 (vs 0) was also associated with significantly higher cost per dose interval. Conclusions: In this population, monthly costs exclusive of drug were significantly lower during the treatment period than in subsequent periods. Unfavorable ECOG PS was associated with significant increases in cost per dose interval. Grade 3/4 adverse events were associated with a marked increase in healthcare costs, but occurred in a small proportion of dose intervals.

Introduction: Neurotoxicity is a major adverse event (AE) of CAR-T therapy with diverse presentation. When severe, it can be fatal, and may lead to neurologic sequelae as well as contribute to increased health care utilization, driving up cost of therapy. In clinical trials, the most common neurologic AEs with axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel) included encephalopathy, headache, tremor, dizziness, aphasia, delirium, insomnia and anxiety. Fatal and serious cases of cerebral edema, leukoencephalopathy and/ or seizures have been reported with both agents. In this real-world analysis, we reviewed post-marketing case reports from the FDA Adverse Events Reporting System (FAERS). Database involving axi-cel or tis-cel for large B cell lymphoma (LBCL), with the dual objectives of characterizing the various components of neurotoxicity and assessing the association of neurological (neuro) AEs with demographic and treatment factors as well as with other AEs reported with CAR-T cell therapy use. Methods: The FAERS database contains anonymized reports of product-related AEs, classified using the Medical Dictionary for Regulatory Activities (MedDRA) and categorized as serious or non-serious. The FAERS database was queried for cases involving axi-cel or tis-cel (and their respective trade names) from the FDA approval date for the LBCL indication (October 18, 2017 for axi-cel; May 1, 2018 for tis-cel) through March 31, 2019. Cases were excluded if patient age was unknown or if the case was reported outside the US. Of all patients reported to have neuro AEs, the frequency of various components was collected. The association of neuro AEs with patient age, concomitant AEs and key lab abnormalities were evaluated by Fisher's exact test, using a two-sided α=0.05 to determine statistical significance. Median age in each subgroup was compared using the Mann-Whitney U test. Results: In the 397 case reports identified, the majority of reactions (376, 95%) were classified as serious. Overall, 258 (65%) were reported to have neuro AEs, with "neurotoxicity" reported in 170 cases (66%); encephalopathy including CAR-T cell-related, metabolic and toxic in 92 cases (36%); seizures including status epilepticus, myoclonus and partial seizures in 12 cases (5%); stroke including cerebrovascular accident, hemiparesis, basal ganglia, brain stem, cerebellar and cerebral infarcts, motor dysfunction, facial and cranial nerve paralysis in 13 cases (5%); speech disorders including terms of aphasia, dysarthria, speech and language impairment in 55 cases (21%); amnesia and memory impairment in 18 cases (7%); brain or spinal cord edema and increased intracranial pressure in 6 cases (2%). Peripheral neuropathy was reported in 5 cases (2%). Symptoms of headache, tremors, dizziness and somnolence were reported in 30 (12%), 41 (16%) 3 (1%) and 34 (13%) cases respectively. Confusional state, delirium or agitation were reported in 61 cases (24%). Neuro AEs were associated with use of axi-cel vs. tis-cel (69% vs. 24%, p 0.05). Conclusions: Neuro AEs were common with CAR-T cell therapy in the real world and largely resembled those reported in clinical trials. Neuro AEs were associated with the agent used, age ≥65 as well as the presence of CRS, cardiac and psychiatric AEs but not with any of the laboratory values studied. The limitations of this study include its retrospective nature, potential under-reporting to FAERS and the relatively small number of patients in the tis-cel group due to its later approval and shorter time available for uptake compared to axi-cel. Despite these limitations, our findings can serve to inform clinicians' decision making when treating adult patients with CAR-T cell therapy. Further research is needed to better discern the etiopathology and biomarkers of neuro AEs in CAR-T cell therapy. Disclosures Gajra: Cardinal Health: Employment. Zettler:Cardinal Health: Employment. Phillips Jr.:Cardinal Health: Employment. Klink:Cardinal Health: Employment. Kish:Cardinal Health: Employment. Mehta:Cardinal Health: Employment. Feinberg:Cardinal Health: Employment.

Introduction: Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel) are chimeric antigen receptor (CAR) T-cell therapies that target CD19-expressing B cells. Both therapies have been approved by the United States (US) Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after at least 2 lines of systemic therapy. The median age at diagnosis of diffuse LBCL is 66 years, with over half the cases occurring in patients over age 65. Patients >65 years have worse survival than younger patients. Despite this predilection for older age, only one quarter of the patients in the pivotal trials supporting approval of the 2 therapies were age 65 or older. An analysis of the safety of axi-cel in the pivotal ZUMA-1 trial showed no significant differences between the age Methods: The FAERS database contains anonymized reports of product-related AEs, classified using the Medical Dictionary for Regulatory Activities (MedDRA) and categorized as serious or non-serious. The database was queried for cases involving axi-cel or tis-cel (and their respective trade names) from the FDA approval date for the LBCL indication (October 18, 2017 for axi-cel; May 1, 2018 for tis-cel) through March 31, 2019. Cases were excluded if the age of the patient was unknown. Cases reported outside the US were excluded. Patient characteristics and adverse events were summarized using descriptive statistics. Comparisons of rates of AEs by age group were made using Fisher's exact test; statistical significance was determined at a two-sided α=0.05. Results: A total of 397 cases were retrieved (360 involving axi-cel, 37 involving tis-cel). The median age of the patients involved was 62 years (range 18-81), with 153 (39%) of the patients age 65 or older. The vast majority of reactions (376, 95%) reported to FAERS were classified as serious. Overall, 141 (36%) cases resulted in hospitalization; 33 (8%) cases had an outcome categorized as life-threatening; 46 (12%) cases resulted in death; 6 (2%) resulted in disability. The most common reaction in each age group was cytokine release syndrome (CRS), reported in 64% and 56% of patients Conclusions: This large-scale post-marketing report of CAR T-cell therapy associated AEs in the real world suggests differences based on age: patients ≥65 had a higher incidence of neurotoxicity and atrial fibrillation while younger patients had increased incidence of some CRS components, especially pyrexia and tachycardia. There was no demonstrable difference in deaths between the 2 groups, but younger patients had higher rates of hospitalization. This report provides real-world evidence for use of CAR T-cell therapy in patients ≥65 and can inform clinical care based on patterns of AEs observed. Potential under-reporting of cases to the FAERS database, the retrospective design of this study and limited data available in the case reports preclude interpretation of causality. Despite these limitations, our findings identified real-world trends in reported signals that complement clinical trial safety data and support further pharmacoepidemiologic study. Disclosures Zettler: Cardinal Health: Employment. Feinberg:Cardinal Health: Employment. Phillips Jr.:Cardinal Health: Employment. Klink:Cardinal Health: Employment. Mehta:Cardinal Health: Employment. Gajra:Cardinal Health: Employment.

141 Background: Dabrafenib plus trametinib (D+T), ipilimumab plus nivolumab (I+N), and both nivolumab and pembrolizumab (“PD-1 mono”) are approved for the 1L treatment of MM. This study reports real world 1L TTNT for patients receiving these therapies by LDH status. Methods: This was a retrospective, observational study. MM patients initiating 1L treatment with D+T, I+N, or PD-1 monotherapy from Jan-2014 through Jun-2017 were identified from community oncology practices in the U.S. Patients treating oncologist abstracted patient date into case report forms. LDH at initiation of treatment was classified by the provider as normal or abnormal ( > 1x and < 2x ULN or ≥ 2x ULN) according to the reference laboratory. TTNT was calculated from 1L initiation to initiation of second-line (2L). Cox proportional hazard models estimated the risk of initiating 2L (proxy for progression) between groups adjusted for age, gender, brain/liver metastases (mets), number of mets and ECOG-PS. Results: Data for 332 patients were submitted by 53 providers including 51.6% who initiated 2L. Abnormal LDH: D+T = 60.3%, ipi/nivo = 53.0%, PD-1 mono = 35.4%. No differences in the frequency of patients with stage IV M1c, brain mets, ECOG, or discontinuation due to toxicity (8.4% of all patients) were noted between cohorts. TTNT was significantly longer in both normal and abnormal LDH cohorts for D+T (14.1 and 11.6 mo.) vs. ipi/nivo (10.1 and 10.2 mo.) but not PD-1 mono (13.3 and 10.6). Adjusted for confounding variables in the abnormal LDH cohort the hazard ratio (HR) for risk of 2L initiation was significantly higher (2.08, p < 0.01) for ipi/nivo vs. D+T but not significant different among normal LDH patients (HR = 1.89, p = 0.054). No significant difference in the risk of 2L initiation between D+T and ipi/nivo were noted in either the normal or abnormal cohorts. Conclusions: For normal and abnormal LDH cohorts 1L TTNT was longer for patients receiving D+T vs. ipi/nivo (but not vs. PD-1 mono). Using the multivariate model we observed the risk of 2L initiation, a proxy for progression, was higher for ipi/nivo treated vs. D+T adjusted for clinical factors for abnormal LDH patients.

Objective This study compared the effectiveness and safety of second generation (atypical) antipsychotic (SGA) versus traditional mood stabilizers (MS) in children and adolescents with bipolar disorder. Methods The study was a retrospective cohort study on 5 years (2003–2007) of Medicaid claims data from four geographically diversified states. Children and adolescents aged 6–18 years who initiated a new treatment episode for bipolar disorder on either an SGA or an MS were followed for 12 months to compare the effectiveness and safety between the two therapeutic categories for pediatric bipolar disorder (PBD). The outcome measures were psychiatric hospital admission, all cause medication discontinuation and treatment augmentation. Potential selection bias caused by unobserved confounding was addressed with instrumental variable methods, using physician prescribing preference and year of cohort entry as the instruments. Sensitivity analysis was conducted to test the robustness of findings against the uncertainties on PBD diagnosis. Results Of the 7423 bipolar children and adolescents identified, 66.60% started treatment on SGA, whereas 33.40% initiated on MS. Patients who initiated on MS and SGA had comparable risk of psychiatric hospital admission (HR = 1.172, 95%CI: 0.827–1.660). However, as compared with those who initiated on MS, patients who initiated on SGA were less likely to discontinue the treatment (HR = 0.634, 95%CI: 0.419–0.961) and less likely to receive treatment augmentation (HR = 0.223, 95%CI: 0.103–0.484). Conclusion As compared with MS monotherapy, SGA monotherapy could be a more effective and safer treatment option for PBD. Copyright © 2014 John Wiley & Sons, Ltd.

e21516Background: Combination TT, dabrafenib/trametinib (D+T) or vemurafenib/cobimetinib (V+C) and combination I-O (ipilimumab/nivolumab [I+N]) or PDL1 monotherapy (nivolumab [N] or pembrolizumab [...

e21538Background: D+T, I+N, N and P are approved for the treatment of BRAF+ MM. Without head to head trials of D+T v. I+N or N/P comparative effectiveness of real world outcomes are needed to bette...

C5.0 classifier is optimized using Bayesian theory. The C5.0 algorithm is a classifier that discovers patterns in data and uses them to make accurate predictions. It classifies data objects based on the information gain of its attributes. Though it responds to noisy and missing data, its accuracy can be improved upon. This research work proposes a post pruning decision tree algorithm that will use C5.0 as its base and Bayesian posterior theory as an enhancer. Post pruning is performed by evaluating the decision tree using Bayesian posterior theory. Bayesian theory uses probability to judge the relative validity of hypothesis in terms of noisy and uncertain data. The proposed algorithm attempts to support low memory usage, higher accuracy and improved speed with the help of smaller decision trees. It will also reduce the risks associated with over-fitting.

Background Painful diabetic peripheral neuropathy (pDPN) is prevalent among persons with diabetes and increases over time. Published guidelines recommend a number of medications to treat this condition providing clinicians with a variety of treatment options. This study provides a comprehensive systematic review and meta-analysis of published pharmacologic therapies for pDPN. Methods The published literature was systematically searched to identify randomized, controlled trials of all available pharmacologic treatments for pDPN (recommended or nonrecommended) reporting predefined efficacy and safety outcomes. Bayesian fixed-effect mixed treatment comparison methods were used to assess relative therapeutic efficacy and harms. Results Data from 58 studies including 29 interventions and 11,883 patients were analyzed. Pain reduction over that of placebo on the 11-point numeric rating scale ranged from −3.29 for sodium valproate (95% credible interval [CrI] = [−4.21, −2.36]) to 1.67 for Sativex (−0.47, 0.60). Estimates for most treatments were clustered between 0 and −1.5 and were associated with more study data and smaller CrIs. Pregabalin (≥ 300 mg/day) was the most effective on the 100-point visual analog scale (−21.88; [−27.06, −16.68]); topiramate was the least (−3.09; [−3.99, −2.18]). Relative risks (RRs) of 30% pain reduction ranged from 0.78 (Sativex) to 1.84 (lidocaine 5% plaster). Analysis of the RR ratio of these 2 treatments reveals marginal significance for Sativex (3.27; [1.07, 9.81]), indicating the best treatment is only slightly better than the worst. Relative risks of 50% pain reduction ranged from 0.98 (0.56, 1.52) (amitriptyline) to 2.25 (1.51, 3.00) (alpha-lipoic acid). RR ratio for these treatments was not statistically different (3.39; [0.88, 3.34]). Fluoxetine had the lowest risk of adverse events (0.94; [0.62, 1.23]); oxycodone had the highest (1.55; [1.45, 1.64]). Discontinuation RRs were clustered around 0.8 to 1.5, with those on the extreme having greater uncertainty. Conclusions Selecting an appropriate pDPN therapy is key given the large number of available treatments. Comparative results revealed relative equivalence among many of the studied interventions having the largest overall sample sizes and highlight the importance of standardization of methods to effectively assess pain.

Aim: A recent large pooled survival analysis has shown that ipilimumab (ipi) conveys long-term survival benefit in a significant proportion of patients (pts) with advanced melanoma (mel). We conducted a retrospective study of clinical outcomes and adverse events (AEs) among pts receiving ipi in a real world setting which may define whether longer survival is associated with increased HCRU. The present analysis describes HCRU by length of survival and baseline ECOG status. Methods: This medical chart review comprised adult pts in the US with unresectable stage III/IV mel treated in a community setting with ≥1 dose of ipi 3 mg/kg as first-line monotherapy between 04/2011 and 09/2012. Demographic/clinical characteristics, details of ipi dosing and subsequent therapies, AEs, and HCRU (hospitalizations, emergency department (ED) visits, nursing home stays) were collected. Pts were categorized according to survival ( Results: Data were abstracted from 273 pt charts at 34 sites. As of 12/20/2013, 231 pts had been followed ≥1 year or until death, and 200 had ECOG status recorded. The 4 groups were similar in age (median 64 years), sex (66% male), and race (95% white). More hospitalizations per pt occurred among pts surviving Conclusions: In this population, the rate of resource use was lower among those surviving ≥1 year than among those surviving Healthcare Resource Utilization during Follow-Up, Mean (SD) Survived ≥1 year ECOG 0 N = 55 Survived ≥1 year ECOG ≥1 N = 51 Survived ECOG 0 N = 26 Survived ECOG ≥1 N = 68 Hospitalizations Number per pt per 100 days* Total days per pt per 100 days * 0.08 (0.16) 0.49 (1.17) 0.09 (0.19) 0.35 (0.79) 0.50 (0.70) 2.22 (3.45) 1.13 (1.77) 5.12 (8.93) Emergency department visits, number per pt per 100 days 0.01 (0.05) 0.02 (0.11) 0 (0) 0.02 (0.07) Nursing home stays Pts (%) Total days per pt per 100 days 1.8% 0.04 (0.30) 5.9% 0.46 (2.01) 7.7% 1.63 (7.20) 7.4% 1.89 (9.00) * p Disclosure: A. Tarhini: Advisory boards: Bristol-Myers Squibb, Merck, and Genentech; Corporate-sponsored research: Bristol-Myers Squibb, Merck, Novartis, Amgen, and Prometheus. A.S. Rao: Employee of Bristol-Myers Squibb. S. Corman: Employee of Pharmerit International; consulting fee or honorarium paid by Bristol-Myers Squibb to Pharmerit International. M. Botteman: employee of Pharmerit International; consulting fee from Bristol-Myers Squibb during the conduct of the study. S. Mehta: employee of Pharmerit International; consulting fee or honorarium paid by Bristol-Myers Squibb to Pharmerit International. X. Ji: employee of Pharmerit International; consulting fee or honorarium paid by Bristol-Myers Squibb to Pharmerit International. M. Katyal: Employee of Medical Data Analytics; corporate-sponsored research: Medical Data Analytics is consultant vendor to Bristol-Myers Squibb, Inc., the financial sponsor of this research study. K. Margolin: Corporate-sponsored research: GlaxoSmithKline, Bristol-Myers Squibb, Genentech, Pfizer, Altor, and Prometheus.