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Title:
A Review of Two Regulatory Approved Anti-CD19 CAR T-Cell Therapies in Diffuse Large B-Cell Lymphoma: Why Are Indirect Treatment Comparisons Not Feasible? | Advances in Therapy
Description:
Anti-CD19 chimeric antigen receptor (CAR) T-cell therapies can be effective for diffuse large B-cell lymphoma (DLBCL), a cancer with limited treatment options and poor outcomes, particularly for patients with relapsed or refractory (r/r) disease. Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CAR T-cell therapies approved by regulatory bodies for certain patients with r/r DLBCL on the basis of demonstrated treatment effects in their pivotal single-arm trials, ZUMA-1 and JULIET, respectively. In the absence of head-to-head trials, the question of whether a valid indirect treatment comparison (ITC) between axi-cel and tisa-cel could be performed using existing evidence is of interest to patients, physicians, payers, and other stakeholders. This article addresses that question by summarizing the current evidence from clinical trials and real-world studies and discussing the challenges and limitations of potential analytical approaches associated with an ITC. Two ITC approaches attempting to adjust for cross-trial heterogeneity between ZUMA-1 and JULIET, matching-adjusted indirect comparison and regression-prediction model analysis, were evaluated. After evaluating the current clinical trial data and real-world evidence, and present and prior ITC analyses of axi-cel and tisa-cel, the authors conclude that a valid comparative analysis is not currently feasible. The substantial differences (e.g., timing of leukapheresis and enrollment, use of bridging chemotherapy [90% in JULIET vs. 0% in ZUMA-1], lymphodepleting regimens) between the two trials’ designs and patient populations preclude a robust and reliable ITC. No other approaches are able to account for such differences. The current real-world data are still too immature to be used for ITCs. Thus, drawing conclusions from such ITCs should be avoided to prevent misinforming treatment choices or limiting patient access to effective treatment options. Additional data from ongoing or future real-world studies with appropriate statistical analyses are needed to provide insights into the comparative effectiveness and safety of these two treatments.
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Keywords {🔍}
patients, article, tisacel, trials, data, juliet, car, treatment, zuma, patient, scholar, tcell, axicel, google, clinical, therapy, realworld, lymphoma, pubmed, outcomes, bridging, therapies, trial, differences, studies, bcell, itc, comparative, chemotherapy, dlbcl, large, indirect, evidence, blood, analysis, access, model, study, care, health, received, infusion, diffuse, comparison, characteristics, axicabtagene, ciloleucel, approaches, analyses, accessed,
Topics {✒️}
uk/wp-content/uploads/2018/08/population-adjustment-tsd-final-ref-rerun uk/wp-content/uploads/2018/05/rwd-dsu-report-updated-december-2016 uk/wp-content/uploads/2016/03/tsd17-dsu-observational-data-final org/newsletter/content/patient-access-medicines-growing-challenge i-report-patients-treated-car-t-cells-ebmt-registry int/selection_medicines/committees/expert/20/applications/diffuselargebcelllymphoma uk/guidance/ta319/resources/guidance-ipilimumab org/indication-data/market-access-report/ granulocyte-macrophage colony-stimulating factor gov/2020/topics-objectives/topic/access cd19 car t-cell chimeric antigen receptor car t-cell therapies anti-car immune response car t-cell therapy double/triple hit lymphoma car t-cells bind car t-cell treatment maic matching-adjusted indirect comparison car t-cell infusion b-cell lymphomas james signorovitch & eric wu anti-cd19 bispecific car t-cell treatments double/triple gene hits open-label single-arm trials autologous-hematopoietic-cell-transplantation de/downloads/92-975-2746/2018-10-31_modul4a_axicabtagen-ciloleucel relapsed/refractory large matching-adjusted indirect comparison t-cell therapies uk/guidance/ta410 t-cell therapy org/magazine/vol9_issue2/patient_access_to_necessary_and_appropriate_medical_care tisa-cel patient-level data population-adjusted indirect comparisons autologous t-cells utilizing patient-level data previously-untreated-advanced-unresectable car t-cells future real-word studies /blog/navigating-patient-access axi-cel axicabtagene ciloleucel axi-cel axicabtagene ciloleucel current real-world timelines indirectly compare tisa-cel ich topic e10—choice future real-world studies van den neste current real-world data
Questions {❓}
- A Review of Two Regulatory Approved Anti-CD19 CAR T-Cell Therapies in Diffuse Large B-Cell Lymphoma: Why Are Indirect Treatment Comparisons Not Feasible?
- A Review of Two Regulatory Approved Anti-CD19 CAR T-Cell Therapies in Diffuse Large B-Cell Lymphoma: Why Are Indirect Treatment Comparisons Not Feasible?
- Diffuse large B-cell lymphoma: R-CHOP failure-what to do?
- How do I report on patients treated with CAR-T cells to the EBMT Registry?
- No head-to-head trial?
- What was learned from this study?
- Why carry out this study?
Schema {🗺️}
WebPage:
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headline:A Review of Two Regulatory Approved Anti-CD19 CAR T-Cell Therapies in Diffuse Large B-Cell Lymphoma: Why Are Indirect Treatment Comparisons Not Feasible?
description:Anti-CD19 chimeric antigen receptor (CAR) T-cell therapies can be effective for diffuse large B-cell lymphoma (DLBCL), a cancer with limited treatment options and poor outcomes, particularly for patients with relapsed or refractory (r/r) disease. Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CAR T-cell therapies approved by regulatory bodies for certain patients with r/r DLBCL on the basis of demonstrated treatment effects in their pivotal single-arm trials, ZUMA-1 and JULIET, respectively. In the absence of head-to-head trials, the question of whether a valid indirect treatment comparison (ITC) between axi-cel and tisa-cel could be performed using existing evidence is of interest to patients, physicians, payers, and other stakeholders. This article addresses that question by summarizing the current evidence from clinical trials and real-world studies and discussing the challenges and limitations of potential analytical approaches associated with an ITC. Two ITC approaches attempting to adjust for cross-trial heterogeneity between ZUMA-1 and JULIET, matching-adjusted indirect comparison and regression-prediction model analysis, were evaluated. After evaluating the current clinical trial data and real-world evidence, and present and prior ITC analyses of axi-cel and tisa-cel, the authors conclude that a valid comparative analysis is not currently feasible. The substantial differences (e.g., timing of leukapheresis and enrollment, use of bridging chemotherapy [90% in JULIET vs. 0% in ZUMA-1], lymphodepleting regimens) between the two trials’ designs and patient populations preclude a robust and reliable ITC. No other approaches are able to account for such differences. The current real-world data are still too immature to be used for ITCs. Thus, drawing conclusions from such ITCs should be avoided to prevent misinforming treatment choices or limiting patient access to effective treatment options. Additional data from ongoing or future real-world studies with appropriate statistical analyses are needed to provide insights into the comparative effectiveness and safety of these two treatments.
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description:Anti-CD19 chimeric antigen receptor (CAR) T-cell therapies can be effective for diffuse large B-cell lymphoma (DLBCL), a cancer with limited treatment options and poor outcomes, particularly for patients with relapsed or refractory (r/r) disease. Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CAR T-cell therapies approved by regulatory bodies for certain patients with r/r DLBCL on the basis of demonstrated treatment effects in their pivotal single-arm trials, ZUMA-1 and JULIET, respectively. In the absence of head-to-head trials, the question of whether a valid indirect treatment comparison (ITC) between axi-cel and tisa-cel could be performed using existing evidence is of interest to patients, physicians, payers, and other stakeholders. This article addresses that question by summarizing the current evidence from clinical trials and real-world studies and discussing the challenges and limitations of potential analytical approaches associated with an ITC. Two ITC approaches attempting to adjust for cross-trial heterogeneity between ZUMA-1 and JULIET, matching-adjusted indirect comparison and regression-prediction model analysis, were evaluated. After evaluating the current clinical trial data and real-world evidence, and present and prior ITC analyses of axi-cel and tisa-cel, the authors conclude that a valid comparative analysis is not currently feasible. The substantial differences (e.g., timing of leukapheresis and enrollment, use of bridging chemotherapy [90% in JULIET vs. 0% in ZUMA-1], lymphodepleting regimens) between the two trials’ designs and patient populations preclude a robust and reliable ITC. No other approaches are able to account for such differences. The current real-world data are still too immature to be used for ITCs. Thus, drawing conclusions from such ITCs should be avoided to prevent misinforming treatment choices or limiting patient access to effective treatment options. Additional data from ongoing or future real-world studies with appropriate statistical analyses are needed to provide insights into the comparative effectiveness and safety of these two treatments.
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Diffuse large B-cell lymphoma
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Internal Medicine
Oncology
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Rheumatology
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