Protocol for a mixed-methods study to develop and feasibility test a digital system for the capture of Patient-Reported Outcomes (PROs) in patients receiving Chimeric Antigen Receptor T-cell (CAR-T) therapies (The PRO-CAR-T Study)

Introduction: Chimeric antigen receptor (CAR) T-cell therapies are novel, potentially curative therapies for haematological malignancies. CAR T-cell therapies are associated with severe toxicities, meaning patients require monitoring during acute and postacute treatment phases. Electronic patient-reported outcomes (ePROs), self-reports of health status provided via online questionnaires, can complement clinician observation with potential to improve patient outcomes. This study will develop and evaluate feasibility of a new ePRO system for CAR-T patients in routine care. Methods and analysis: Multiphase, mixed-methods study involving multiple stakeholder groups (patients, family members, carers, clinicians, academics/researchers and policy-makers). The intervention development phase comprises a Delphi study to select PRO measures for the digital system, a codesign workshop and consensus meetings to establish thresholds for notifications to the clinical team if a patient reports severe symptoms or side effects. Usability testing will evaluate how users interact with the digital system and, lastly, we will evaluate ePRO system feasibility with 30 CAR-T patients (adults aged 18+ years) when used in addition to usual care. Feasibility study participants will use the ePRO system to submit self-reports of symptoms, treatment tolerability and quality of life at specific time points. The CAR-T clinical team will respond to system notifications triggered by patients’ submitted responses with actions in line with standard clinical practice. Feasibility measures will be collected at prespecified time points following CAR T-cell infusion. A qualitative substudy involving patients and clinical team members will explore acceptability of the ePRO system. Ethics and dissemination: Favourable ethical opinion was granted by the Health and Social Care Research Ethics Committee B(HSC REC B) (ref: 23/NI/0104) on 28 September 2023. Findings will be submitted for publication in high-quality, peer-reviewed journals. Summaries of results, codeveloped with the Blood and Transplant Research Unit Patient and Public Involvement and Engagement group, will be disseminated to all interested groups. Trial registration number: ISCTRN11232653

Development of a conceptual framework for an electronic patient-reported outcome (ePRO) system measuring symptoms and impacts of CAR-T cellular therapies in patients with haematological malignancies:A rapid review

Chimeric antigen receptor T-cell (CAR-T) therapy is associated with potentially severe toxicities that pose significant burden. Patient-reported outcomes (PROs) offer valuable insights into symptoms, functioning and other complex constructs of interest. This rapid review aimed to: 1) identify symptom and impact concepts important to CAR-T patients; 2) construct a conceptual framework for an electronic patient-reported outcome (ePRO) system; and 3) identify timepoints to capture PRO data for CAR-T cell therapies. We searched MEDLINE (OVID) and Web of Science (Clarivate) for English articles published from 2017 to Mar 2, 2023. No restrictions on study design were applied. 178 symptoms/constructs were extracted from 44 articles reporting PRO collection in adults with hematologic malignancies receiving CAR-T cell therapy. Six healthcare professionals and 11 patients and caregiver partners verified construct relevance to clinical management and lived experience respectively. 109 constructs were sorted according to the four domains of conceptual framework: Symptom Burden, Impact of Disease and Treatment, Tolerability, and Health-Related Quality of Life. The identification of concepts beyond symptom burden underscores the importance of PRO measurement for long-term monitoring, to align outcomes with patient concerns. The framework will facilitate PRO measure selection for systematic gathering of PROs from individuals with haematological malignancy receiving CAR-T cell therapies

Development of a conceptual framework for an electronic patient-reported outcome (ePRO) system measuring symptoms and impacts of CAR-T cellular therapies in patients with haematological malignancies:A rapid review

Chimeric antigen receptor T-cell (CAR-T) therapy is associated with potentially severe toxicities that pose significant burden. Patient-reported outcomes (PROs) offer valuable insights into symptoms, functioning and other complex constructs of interest. This rapid review aimed to: 1) identify symptom and impact concepts important to CAR-T patients; 2) construct a conceptual framework for an electronic patient-reported outcome (ePRO) system; and 3) identify timepoints to capture PRO data for CAR-T cell therapies. We searched MEDLINE (OVID) and Web of Science (Clarivate) for English articles published from 2017 to Mar 2, 2023. No restrictions on study design were applied. 178 symptoms/constructs were extracted from 44 articles reporting PRO collection in adults with hematologic malignancies receiving CAR-T cell therapy. Six healthcare professionals and 11 patients and caregiver partners verified construct relevance to clinical management and lived experience respectively. 109 constructs were sorted according to the four domains of conceptual framework: Symptom Burden, Impact of Disease and Treatment, Tolerability, and Health-Related Quality of Life. The identification of concepts beyond symptom burden underscores the importance of PRO measurement for long-term monitoring, to align outcomes with patient concerns. The framework will facilitate PRO measure selection for systematic gathering of PROs from individuals with haematological malignancy receiving CAR-T cell therapies

Integrated genomic characterization of endometrial carcinoma

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ~25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.National Institutes of Health (U.S.) (Grant 5U24CA143799-04)National Institutes of Health (U.S.) (Grant 5U24CA143835-04)National Institutes of Health (U.S.) (Grant 5U24CA143840-04)National Institutes of Health (U.S.) (Grant 5U24CA143843-04)National Institutes of Health (U.S.) (Grant 5U24CA143845-04)National Institutes of Health (U.S.) (Grant 5U24CA143848-04)National Institutes of Health (U.S.) (Grant 5U24CA143858-04)National Institutes of Health (U.S.) (Grant 5U24CA143866-04)National Institutes of Health (U.S.) (Grant 5U24CA143867-04)National Institutes of Health (U.S.) (Grant 5U24CA143882-04)National Institutes of Health (U.S.) (Grant 5U24CA143883-04)National Institutes of Health (U.S.) (Grant 5U24CA144025-04)National Institutes of Health (U.S.) (Grant U54HG003067-11)National Institutes of Health (U.S.) (Grant U54HG003079-10)National Institutes of Health (U.S.) (Grant U54HG003273-10