New protocols, remote patient monitoring, and improved standards of care among ways industry can take next steps in CAR T-cell research.
Chimeric antigen receptor (CAR) T-cell therapies have demonstrated inspiring clinical results for the treatment of various cancers, including advanced leukemias and lymphomas, for several years.1
FDA has approved six CAR T-cell therapies for the treatment of various cancers since 2017, and most recently, multiple myeloma. Nearly 1,200 trials were under way as of August 2023 (based on ClinicalTrials.gov) to study the treatment’s therapeutic effect on brain, colorectal, pancreatic, renal and other types of cancer.2,3
Although CAR T-cell therapies are highly effective against cancer and have the potential to be successful against many more, the therapy is not without risks. It possesses a unique set of acute toxicities that include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which can be fatal in a few cases and require close management following treatment. As a result, patients often need to stay in the hospital for a week or longer following treatment so they can be closely monitored. While CRS is a common reaction, serious CRS (grades 3 or higher) occur in as few as 2% of patients and as many as 22%, according to a review of clinical studies.4
Certainly, hospital-level surveillance is warranted after a treatment with such risks, but does it need to be in a hospital facility? As an example, Vanderbilt University’s Ingram Cancer Center is examining whether patients with lymphoma can be safely and effectively monitored in a home-like setting using wearables along with artificial intelligence (AI)-based predictive analytics to notify clinicians if a patient is likely to decompensate and requires a clinical intervention. The trial, which was recruiting participants as of early spring 2023, is intended to explore the feasibility of treating subjects with a specific CAR-T therapy in the outpatient setting and guide the development of guidelines by which the treatment in the outpatient setting can be done safely. More details on this study are discussed later.5
Other leading clinical research institutions, such as Cleveland Clinic, are also studying how CAR T-cell therapies can be safely delivered on an outpatient basis.6 Not only are these leading healthcare organizations interested in avoiding hospitalizations, but eliminating the need for an admission means that these life-extending treatments could be more feasibly extended to communities that currently lack access.
In a prospective real-world study that included a cohort of 367 patients (169 admitted to a hospital-at-home program post-discharge and 198 receiving usual care), researchers concluded that the hospital-at-home program shows initial promise as a model for oncology care that may lower unplanned healthcare utilization and healthcare costs.7 In propensity-weighted analyses, the odds of unplanned hospitalizations were reduced in the home group by 55% and healthcare costs were 47% lower over 30 days.
If based on this line of research hospital at home and remote patient monitoring (RPM) becomes the new standard of care following CAR T-cell therapy, it could significantly reduce healthcare spending and improve outcomes—while vastly improving the treatment and recovery experience for patients.
Across the care continuum—acute, post-acute and chronic condition management—clinical care is shifting to patients’ homes, and RPM is becoming increasingly commonplace. RPM, combined with advanced analytics (such as artificial intelligence [AI] and machine learning [ML] algorithms) to process the high volume of patient data, has become the foundational capability that is accelerating this shift to care at home. Nearly 71 million Americans are expected to engage in some type of RPM by 2025—which involves collecting vitals and biometrics data in the real world, outside a traditional care setting, and sharing it electronically with a provider.8
Similar to clinical care shifting to patients’ homes, clinical research is starting to leverage advances in RPM and moving towards fully or partially virtual clinical trials, also referred to as decentralized clinical trials (DCTs). Among pharmaceutical and biotech companies, DCT usage increased by 11 percentage points in 2022 and was expected to increase another 13 percentage points over the next two years.9
Yet monitoring conditions such as heart failure, diabetes, chronic obstructive pulmonary disease and others where many patients may be otherwise healthy and well-managed with medication and behavioral change can vary greatly from monitoring patients with cancer, especially those receiving CAR T-cell therapy. Often, the therapy is applied when no other treatments have been effective. Patients can be older adults who are frail, but they can also be younger adults and children who, although sick, are still active. Not only do these patients not want to be in a hospital—they don’t need to be.
Yet due to the risk of a serious adverse event, few patients receive the therapy outside a hospital, even though a 2020 study found that outpatient administration of the therapy was associated with a $32,987 (40.4%) reduction in total costs.10,11
Accommodating patient and family preferences by delivering treatments at home would likely also help reduce healthcare spending—and related clinical studies. Decentralizing trials involving CAR T-cell therapy could also ease recruitment by pulling from a larger population spread across a geographical area, which would also increase the diversity of the cohort—and could encourage participation by enabling patients to recover at home.
The Vanderbilt clinical trial (which leverages virtual care and a digital clinical research platform from Biofourmis) focuses on patients with large B-cell lymphoma receiving the CAR T-cell therapy. Instead of remaining in the hospital after receiving immunotherapy, patients are discharged to a home-like setting near the medical center.
The primary objective of the initial study is to evaluate the feasibility of treating subjects in the outpatient setting, which could then guide the development of a subsequent, larger study that will determine the tolerability and safety profile of the treatment in the outpatient setting supported by an RPM platform. Investigators will also determine the time to specific interventions post-infusion and the number of subjects who remain outpatient through 3, 7, 14, and 30 days.
Off-site, patients receive periodic “house calls” from clinicians that include physical exams. In between those in-person encounters, patients enter their blood pressure every four to six hours into a patient-facing app on a mobile device. Their other vital signs, including heart rate, body surface temperature, oxygenation levels, respiratory rate and others, are continuously collected around the clock through biosensors and analyzed by investigators. On a continuously updated dashboard, clinicians and researchers can evaluate the patient’s trajectory at a glance. They also receive notifications when physiologic signals deviate from an established, personalized baseline developed through machine learning and/or if a study participant has not entered required blood pressure readings.
Clinicians may then intervene based on data received through the RPM technology either in-person, by phone or through a video visit. As an exploratory objective, Vanderbilt researchers are tracking the frequency of abnormal vital signs, and the analytics will be used to identify trends in hospitalization and other outcomes.
In earlier trials, as well as real-world care delivery settings, researchers have demonstrated that the AI-based RPM technology used in the Vanderbilt study can help clinicians identify the early signs of clinical decompensation across various disease areas, enabling early interventions for better outcomes and lower cost of care. Establishing clear, reliable RPM guidelines for patients receiving CAR T-cell therapy, thanks to this study and related future investigations, would be a major achievement in cancer research and treatment.12,13
When a patient is monitored in the hospital following CAR-T therapy, clinicians perform all the tests and data entry during their rounds. When patients are monitored at home, the patient and/or their family caregiver shares in that responsibility. Technology can automate some activities, such as collecting data from biosensors and analysis and reminding the patient to perform activities, but patients and families also need to be engaged in the care plan and perform associated duties.
Patients and families, especially those facing cancer, are under enormous stress. Certainly, it is comforting to patients when they are in a home setting surrounded by family and a familiar environment. To further improve their experience and foster engagement, easy-to-understand and highly usable patient-facing technology is essential—especially when it comes to data entry, completing questionnaires, and virtual visits.
As all researchers know, greater participant adherence ensures that the information gathered is accurate and reliable, which can yield more meaningful results. Ultimately, the goals of clinicians and researchers are the same: to improve patient outcomes and experiences. CAR T-cell therapy is the first step in achieving these goals in patients with certain cancers. Shifting the recovery venue to the home and supporting patients with a simple, effective, engaging and reassuring remote management plan can take the next step while improving the experience for everyone involved.
Jaydev Thakkar, MBA, MCA, is chief operating officer of Biofourmis