Multimodal Telerehabilitation in Patients Undergoing CAR-T Cell Immunotherapy

CAR-T therapy is a relatively new, innovative treatment strategy to manage refractory hematological cancers, including some types of leukemia, lymphoma, and multiple myeloma (Efficace, 2022). This pivotal treatment has become a standard-of-care for certain malignancies, such as relapsed non-Hodgkins lymphoma, relapsed or refractory acute lymphoblastic leukemia, and relapsed refractory multiple myeloma, with some studies showing at least 80% of the patients with a positive response to treatment (June, 2018; Landry, 2020). While CAR T-cell therapy has led to significant advances in the treatment of hematologic malignancies, it also presents a set of unique toxicities. The two most common acute adverse effects are cytokine release syndrome (CRS) and neurological toxicity known as immune effector cell-associated neurotoxicity syndrome (ICANS), respectively (Neelapu, 2017).

Recent studies suggest that there should be an emphasis on prehabilitation soon after initiating the workup process for CAR-T therapy, maintaining function during active treatment, and close follow-up with rehabilitation especially if neurological sequelae persist (Obaisi, 2022; Kiefer, 2023). Effective interventions are urgently needed to improve the QoL and functional capacity in patients with hematological cancers undergoing CAR-T therapy (Cenik, 2020;Jeevanantham, 2021). Physical activity programs have been shown to impact psychological symptoms, fatigue, and quality of life (Vermaete, 2013, 2014). Crucially, no evidence has been presented to date for patients with hematologic malignancies while undergoing CAR-T therapy. Thus, studies exploring approaches to expand access to multimodal cancer rehabilitation practices in these patients are necessary to address the needs of the rapidly growing population of cancer survivors receiving CAR-T therapy. Recent systematic reviews demonstrated the high potential of telehealth approaches to facilitate cancer rehabilitation (Brick, 2022; Chang, 2022).

Home Automated Telemanagement (HAT). The HAT system is a telemedicine platform supporting patients in following individualized self-care plans and assisting healthcare practitioners in the treatment and monitoring of their patients according to evidence-based guidelines (Finkelstein, 2012; Fleg, 2020; Shero, 2022). HAT is based on the chronic disease care model (Grover, 2014) and provides support for patient self-management, comprehensive patient-provider communication, and multidisciplinary care coordination (Drouin, 2015). The main objective of the HAT system is to minimize the burden of chronic disease management and to simplify monitoring in ambulatory care. To achieve this goal, the HAT system is required (1) to support a constant information feedback loop between the patient and health care providers; (2) to take over all routine repetitive tasks; and (3) to provide real-time clinical decision support both for the patient and clinician. HAT has been successfully implemented and tested in a variety of chronic diseases.

Patient units are used at patient homes to guide patients in following their treatment plans including exercise and diet prescriptions, monitor patients' progress and symptoms, and to communicate with health care providers. Any web-enabled device can serve as a patient unit including touchscreen tablets, VR headsets, and smartphones. The home unit interface underwent rigorous usability testing (Jeong, 2015; Finkelstein, 2021; Gabriel, 2023) and is very simple to operate, even by those without any prior computer experience. The clinician units (any web-enabled device) are used to set up and update individualized treatment plans, analyze patient self-testing results, and review computer-generated alerts. The HAT server implements computerized decision support based on individualized alert setup and realtime monitoring of patient self-testing data. In this study, the HAT system will be focused on the delivery of a multimodal cancer rehabilitation program comprising individualized therapeutic physical exercise, nutrition plan, behavioral counseling, and tailored educational empowerment targeting the social, cognitive, reproductive, and vocational needs of blood cancer survivors.

The proposed multimodal telerehabilitation model allows a rehabilitation therapy team to set up individualized rehabilitation plans using a web-based care management portal and monitor patient progress online. Patients at home follow a safe and effective personalized exercise and nutrition plan guided by interactive touch-screen technology combined with behavioral counseling, social support, and interactive education and empowerment. The design of the telerehabilitation system is based on the cloud-based Internet-of-Things architecture allowing real-time monitoring of cardiovascular parameters and exercise performance. The patient's level of exertion during exercise is automatically identified by a validated AI-driven algorithm supporting exercise safety and efficacy. The ultimate goal of this pilot feasibility project is to establish the extent of the impact of the proposed patient-centered cancer telerehabilitation model on disease-specific quality of life, and functional and symptom outcomes and to obtain sufficient evidence for a definitive randomized clinical trial evaluating this approach in a multi-center study.