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Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are autologous anti-CD19 chimeric antigen receptor T (CAR T) cell therapies for the treatment of patients with relapsed/refractory large B cell lymphoma (RR-LBCL). Both can induce durable responses; however, cross-trial comparisons are difficult due to differences in study design. In this study, the registration trials of axi-cel and tisa-cel were compared using a matching adjusted indirect comparison (MAIC). A MAIC was performed to adjust for differences in patient characteristics between trials. The estimates for the ZUMA-1 (axi-cel) trial were adjusted using patient-level data to match the study population in JULIET (tisa-cel) for key variables: International Prognostic Index), Eastern Cooperative Oncology Group score, stage, refractoriness or relapsed disease, double/triple hit status, cell of origin, and number of prior lines of therapy. The endpoints analyzed were response, overall survival (OS), and adverse events. After adjusting for differences in patient characteristics between trials, axi-cel was associated with a greater objective response rate (relative risk [RR]=1.61; 95% confidence interval [CI], 1.29 to 2.01) and complete response (RR = 1.62; 95% CI, 1.16 to 2.27) than tisa-cel among patients who underwent infusion. The OS from infusion onward comparing axi-cel to tisa-cel had a hazard ratio of 0.51 (95% CI, 0.31 to 0.83). The indirect comparison showed a higher rate of grade 1 to 2 cytokine release syndrome (CRS) in ZUMA-1 compared with JULIET (RR = 2.03; 95% CI, 1.55 to 2.65) and similar rates of grade ≥3 CRS and neurologic events. In the absence of a direct head-to-head study, the MAIC statistical technique suggests axi-cel may have superior efficacy but a greater risk of grade 1 to 2 CRS. Future real-world studies can further inform the relative efficacy and safety of CAR T therapies in RR-LBCL.

Patients treated with anti-CD19 chimeric antigen receptor (CAR) T-cell therapies have shown either sustained remission or rapid progression. Traditional survival modeling may underestimate outcomes in these situations, by assuming the same mortality rate for all patients. To illustrate this issue, we compare standard parametric models to mixture cure models for estimating long-term overall survival in patients with relapsed or refractory large B-cell lymphoma treated with axicabtagene ciloleucel (axi-cel). Compared to standard models without cure proportions, mixture cure models have similar fit, but substantially different extrapolated survival. Standard models (Weibull and generalized gamma) estimate mean survival of 2.0 years (95% CI (1.5, 3.0)) and 3.0 years (95% CI (1.7, 5.6)), respectively, compared to 15.7 years (95% CI (9.3, 21.1)) and 17.5 yrs (12.0, 22.8) from mixture cure models (using Weibull and generalized gamme distributions). For cancer therapies where substantial fractions achieve long term remission, our results suggest that assumptions of the modeling approach should be considered. Given sufficient follow-up, mixture cure models may provide a more accurate estimate of long-term overall survival compared with standard models.

e20070 Background: CAR T therapy is being investigated as 2nd line therapy in RR-DLBCL. To evaluate its impact on patients’ HRQOL, it is essential to understand the HRQOL of patients receiving current standard of care (SOC) therapy for DLBCL and NHL patients. Methods: A systematic literature review (SLR) of studies reporting HRQOL in RR-DLBCL patients was conducted in March 2019 (updated to include RR-NHL in May 2019) using EMBASE, MEDLINE, Cochrane (all from 2007), Northern Light and International Society for Quality of Life Research abstracts (both from 2017). A targeted literature review (TLR) for untreated or 1st line patients was conducted in July 2019 using PubMed. Search terms included diseases, lines of therapy and patient-reported outcome (PRO) measures. Abstracts and publications were screened for eligibility and data were extracted. Results: Of the 977 publications screened for the SLR, 26 met the inclusion criteria. Another 18 studies were included from the TLR. The most commonly used PRO measures were the SF-36 (10 studies), EORTC QLQ-C30 and FACT-Lym (8 studies each). The EORTC QLQ-C30 showed statistically significant or clinically meaningful changes in a greater number of domains (86%) than the FACT-Lym (75%) and SF-36 (62%). Additional results in table. Conclusions: While research is limited, RR-DLBCL patients receiving current SOC therapy report decreases in HRQOL and health utility. Further research is needed on how existing and future therapies may affect HRQOL among RR-DLBCL patients. [Table: see text]

Background Studies demonstrate the potential for statins to prevent dementia and Alzheimer's disease (AD), but the evidence is inconclusive. Objective Conduct a meta-analysis to estimate any benefit of statins in preventing dementia and examine the potential effect of study design and confounding on the benefit of statins in dementia. A secondary goal is to explore factors that may elucidate the mechanisms by which statins exert their potentially beneficial effect. Methods Performed systematic literature review to identify relevant publications. Relative risk (RR) estimates were pooled using both fixed and random effect models. Studies were stratified by study design and potential confounding factors. Results The pooled results for all-type dementia suggest that use of statins is associated with a lower RR of dementia when compared to non-statin users (random effects model: RR 0.82 (95%CI [0.69, 0.97]). The pooled results for AD also suggested a lower RR with statin user compared to non-statin users in random effects models (RR: 0.70, 95% CI [0.60, 0.83]). Study design and methods used to address biases may influence the results. Conclusion These pooled results suggest that statins may provide a slight benefit in the prevention of AD and all-type dementia. This benefit observed in both disease states should be interpreted with caution as observational studies are subject to bias, and it is possible that the slight benefit observed may disappear when these biases are addressed in a well-designed randomized controlled trial. Copyright © 2012 John Wiley & Sons, Ltd.

Introduction Patients with relapsed/refractory large B-cell lymphoma (RR-LBCL) treated with salvage chemotherapy have a poor prognosis, with a median survival of 6.3 months (Crump 2017). Given the recent approval of chimeric antigen receptor T-cell therapies (CAR T) for patients with RR-LBCL, efforts to demonstrate the comparative effectiveness of different CAR Ts are imminent. In the absence of head-to-head trials, such an assessment will likely be based on indirect or between-trial comparisons of reported survival estimates. Due to differences in the multi-step manufacturing process preceding the infusion of CAR T cells, the duration of the pre-infusion period, which accounts for time from leukapheresis to infusion, may vary across CAR Ts. This variability may be associated with differences in the prognostic characteristics of patients who endure the pre-infusion period. As such, comparisons of reported survival among these selected patients with the different CAR Ts evaluated in different trials may be biased. Estimating the comparative effects of CAR T therapies on survival requires careful attention to these potential differences and the use of thoughtful analytic approaches to address bias. We aimed to review current methodological approaches used to address bias related to time-to-treatment initiation and assess their potential utility in comparative analyses of CAR T based on between-trial comparisons. Methods A targeted literature review was performed to identify studies that used methods to adjust for bias related to time-to-treatment initiation when estimating relative treatment effects regarding survival outcomes between interventions in oncology. Relevant studies published in English from 2008 onwards were identified by searching the Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica dataBASE (EMBASE). In addition, manual searches of the reference lists of the identified studies were performed. Studies that provided the most recent application of a proposed method were selected for inclusion. Results We identified several manuscripts that utilized methods to address survival or survival treatment selection bias (STSB) in observational studies where the classification of "treated" individuals required them to have survived until treatment initiation, and individuals who died early without the opportunity to get treatment were classified as "untreated". The identified methods to adjust for the over-estimation of the treatment effect include landmark survival and time-dependent exposure assignment. The landmark method restricts the analysis sample to patients who are event-free and alive at a given point (i.e, landmark) during follow-up; patients are assigned to risk groups based on their status at the landmark and survival outcomes are estimated from that point. Time-dependent exposure assignment addresses STSB by accounting for changes in patient exposure or treatment status during the course of follow-up. All patients begin in the same risk group; when exposure changes, patients and person-time are switched to the applicable risk group at that point. However, these methods do not address bias resulting from a comparison of reported survival estimates between different CAR Ts for a follow-up starting at the successful infusion of the CAR T cells. When comparing CAR Ts, the differences in prognostic patient characteristics due to differences in the pre-infusion phase are similar to channeling bias or confounding-by-indication. These concepts are well known, and established methods are available. However, those methods have limited applicability without access to individual patient data for the CAR Ts of interest. Conclusion Comparing survival upon successful infusion with different CAR Ts reported in separate studies is likely to be biased due to differences in the duration of the pre-infusion period. Methods previously used to address bias related to differences in time-to-treatment initiation may not be relevant or applicable, particularly in the absence of patient-level data. A between-trial comparison of reported survival estimates with the different CAR Ts might benefit from incorporating external evidence to inform the mortality during the pre-infusion periods. Disclosures Katz: Amgen: Other: Former employee and stockholder; Kite, a GILEAD Company: Consultancy. Lin:Kite/Gilead: Employment. Blaylock:Kite, A Gilead Company: Consultancy. Jansen:Kite, A Gilead Company: Consultancy.

ObjectiveTo estimate the relationship between health utilities and body mass index (BMI) among a cohort of obese patients who underwent laparoscopic adjustable gastric banding (LAGB).MethodsWe used a cross-sectional survey to ascertain demographic, clinical, and health utility data from patients who had undergone LAGB in Washington State from 2004 to 2010. The EuroQol five-dimensional (EQ-5D) questionnaire was used for health utility estimation. We calculated adjusted EQ-5D questionnaire indices across BMI categories by using a two-part model. We also used logistic regression to examine the relationship between BMI and the likelihood of reporting problems on each of the EQ-5D questionnaire dimension.ResultsData were obtained from 790 subjects. The mean adjusted EQ-5D questionnaire indices for all obese BMI categories were significantly lower than those in the normal weight category. The relationship between BMI and EQ-5D questionnaire indices was nonlinear. Respondents classified as morbidly obese II (BMI > 50 kg/m2) had the greatest decrement (−0.15, 95% confidence interval −0.28 to −0.01) in EQ-5D questionnaire indices. The association between EQ-5D questionnaire indices and BMI at the time of the survey was weaker after adjusting for weight loss after LAGB. Respondents with higher BMI were more likely to report having problems in the mobility, usual/activity, pain/discomfort, and anxiety/depression dimensions (trend test, P < 0.05), but not for the self-care dimension (trend test, P = 0.08).ConclusionsThe EQ-5D questionnaire has a negative and nonlinear relationship with BMI for obese patients who had LAGB. The relationship is confounded by weight loss. Within the EQ-5D questionnaire dimensions, patients are more likely to report having problems in the mobility, usual/activity, pain/discomfort, and anxiety/depression dimensions in higher BMI categories, but not in the self-care dimension.

Studies demonstrate the potential for statins to prevent dementia and Alzheimer's disease (AD), but the evidence is inconclusive.Conduct a meta-analysis to estimate any benefit of statins in preventing dementia and examine the potential effect of study design and confounding on the benefit of statins in dementia. A secondary goal is to explore factors that may elucidate the mechanisms by which statins exert their potentially beneficial effect.Performed systematic literature review to identify relevant publications. Relative risk (RR) estimates were pooled using both fixed and random effect models. Studies were stratified by study design and potential confounding factors.The pooled results for all-type dementia suggest that use of statins is associated with a lower RR of dementia when compared to non-statin users (random effects model: RR 0.82 (95%CI [0.69, 0.97]). The pooled results for AD also suggested a lower RR with statin user compared to non-statin users in random effects models (RR: 0.70, 95% CI [0.60, 0.83]). Study design and methods used to address biases may influence the results.These pooled results suggest that statins may provide a slight benefit in the prevention of AD and all-type dementia. This benefit observed in both disease states should be interpreted with caution as observational studies are subject to bias, and it is possible that the slight benefit observed may disappear when these biases are addressed in a well-designed randomized controlled trial.

Background There is very little evidence regarding the real world experience and outcomes after laparoscopic adjustable gastric banding (LAGB). Our objective was to estimate the amount of postoperative weight loss, change in co-morbidity status, and complications after LAGB. The setting was LAGB surgical centers in Washington state. Methods A cross-sectional survey was developed to collect primary data from patients who had undergone LAGB in Washington state from 2004 to 2010. The survey contained questions on patient characteristics, weight change, co-morbidities, and complications after LAGB surgery. We used descriptive and other statistical tests to evaluate our key research questions by the period since LAGB. Results A total of 1556 surveys were sent out, and 790 were returned (response rate 50.8%). Responders were categorized into 4 groups according to the follow-up period: 4 years. The corresponding average body mass index reduction in each group was 21.0%, 22.5%, 21.3%, and 20.4%. Of the respondents, 21.7%, 34.8%, 44.6%, and 38.7% indicated they did not have any adjustments in the year preceding the survey. The percentage of respondents who had undergone additional operations related to LAGB was 8.6%. Specifically, 3.6% of the respondents had undergone either band removal or conversion to another type of bariatric operation. Conclusion We found that although LAGB appeared to be beneficial for weight reduction and improving co-morbidities, the underuse of band adjustments and significant rate of treatment failure might limit the long-term effectiveness of LAGB.

OBJECTIVE To compare the efficacy of ustekinumab with that of other biological agents using the Psoriasis Area and Severity Index (PASI) among adult patients with moderate to severe plaque psoriasis. DATA SOURCES We conducted a systematic search of the period January 31, 1992, to February 1, 2012, using MEDLINE (PubMed), Embase, the Cochrane Library, and clinicaltrials.gov. STUDY SELECTION We included randomized controlled trials of biological agents compared with placebo or other biological agents using the PASI in patients who had moderate to severe plaque psoriasis. DATA EXTRACTION Study data were extracted independently by 2 of us, with disagreement resolved by consensus. Data extracted included the size of the trial, follow-up period, age range of patients, disease duration, body surface area involvement, baseline PASI, PASI response, and previous treatment with biological agents. DATA SYNTHESIS A Bayesian network meta-analysis was performed by fitting 3 regression models: a fixed-effects model, a random-effects model, and a random-effects model with meta-regression coefficients. The random-effects model achieved the best fit for these data. In pairwise comparisons, ustekinumab use was associated with statistically significantly higher odds for achieving a 75% reduction in the PASI compared with adalimumab use (odds ratio [OR], 1.84; 95% credible interval [CrI], 1.01-3.54), alefacept use (OR, 10.38; CrI, 3.44-27.62), and etanercept use (OR, 2.07; 95% CrI, 1.42-3.06) but was associated with lower odds compared with infliximab use (OR, 0.36; 95% CrI, 0.14-0.82) . In the therapeutic class comparison, the interleukin-12/23 inhibitor had the highest odds for achieving a 75% reduction in the PASI compared with placebo (OR, 69.48; 95% CrI, 36.89-136.46), followed by tumor necrosis factor inhibitors (OR, 42.22; 95% CrI, 27.94-69.34) and the T-cell inhibitor (OR, 5.63; 95% CrI, 1.35-24.24). CONCLUSION For the treatment of moderate to severe plaque psoriasis, ustekinumab may be more efficacious than adalimumab, etanercept, and alefacept but not infliximab.