The cell therapy industry is in the early stages of growth and development, with only a few having secured regulatory approval. This approval comes with regulatory requirements that ensure safety, including patient outcomes data collection for up to 15 years post-infusion.
While daunting, the strings attached to these first-generation therapy approvals help understand safety and advance next-generation cell therapies as the number of commercially treated patients grows. Specifically, the data captured in patient outcomes registries can help advance new cell therapies when the information is shared across the industry.
This article will discuss the benefits of using existing infrastructure for long-term outcomes collection and how using a single secondary database can improve next-generation therapies and increase patient access to cell therapy.
Building a cell therapy outcomes database infrastructure
Pharmaceutical companies could develop their infrastructure for long-term patient outcomes data capture. However, using existing infrastructure — or secondary database — offers three primary advantages for gathering data:
- Rapid implementation.
- Patient consent.
- Ease of use.
For example, let’s look at the Cellular Immunotherapy Data Resource (CIDR), which is funded by the National Cancer Institute, managed by the CIBMTR (Center for International Blood and Marrow Transplant Research), and part of the Moonshot Initiative to expedite cancer research. CIDR has an established infrastructure to collect data on cellular immunotherapies for cancer. In addition, this infrastructure fulfills the regulatory requirement to monitor the outcomes of therapy recipients.
Studies completed by CIDR — Post Approval Safety Studies (PASS) — seek to understand the safety of cell therapy products in a real-world setting. This is done by creating a prospective observational study with a defined targeted population and sample size.
Therefore, when a new CAR-T therapy becomes commercially available, patients receiving the therapy consent to share their data to a secondary database. This scenario allows data collection to begin rapidly because the mechanism for collecting and analyzing the data already exists.
Alternatively, using a primary database would require developing specific, informed consent implemented at every institution delivering the therapy, ultimately slowing the implementation process.
Finally, relying on a single secondary database provides standardization across the industry. Standardization is a critical factor for healthcare institutions infusing cellular therapies. In addition, having familiarity with one system — versus learning the slight differences between multiple systems — increases the likelihood of data submission.
In addition, collecting the same data points for each therapy allows for an apples-to-apples outcomes comparison. Presently, all approved commercial CAR-T cell therapies in the U.S. for treating hematologic malignancies have an associated PASS protocol with CIDR. These include axicabtagene-autoleucel, tisagenlecleucel, brexucabtagene autoleucel, lisocabtagene autoleucel and idecabtagene vecleucel therapies.
Rapidly disseminating data for research use
Even more important than how information is gathered is how the real-world information in the database can advance future cell therapies. An outcomes registry is not only for regulatory reporting use. A database like the CIDR is a resource for the entire cell therapy community.
While the collected data is shared with the reporting centers and the therapy stakeholders, the general cell therapy community gains access. This aggregate data from real-world practice helps researchers model the development of new clinical trials. In addition, it helps the medical community better understand these products applications.
The biomedical community can propose studies using the data through the CIBMTR study proposal and working committee activities. The CIDR oversees the Cellular Immunotherapy for Cancer Working Committee, which manages most of these study proposals.
As a result, the availability of this resource of real-world data may assist in shortening the time that new cell therapies become approved for patients. In addition, this resource can assist in using the existing data as artificial controls for new therapies and in the use of real-world data to analyze the safety and efficacy of novel cellular therapies derived from approved products but with a better manufacturing process. These are examples of how development time of these therapies might be shortened by using real-world instead of clinical trial data in the future.
Understanding cell therapy toxicity
Therapy developers and clinicians must understand toxicities after administering a cellular therapy like CAR-T cells. A cell therapy outcomes database provides the infrastructure to capture and analyze this information long-term.
For example, the Cellular Therapy Registry contains follow-up forms that are triggered at three, six and 12 months and yearly after that. In addition, event-driven forms on subsequent primary malignancies and pregnancies are also available for centers to report an event at any time.
The forms gather information regarding toxicity — for example, cytokine release syndrome (CRS), neurotoxicity and grading — along with the disease treated, disease response and whether the patient received additional treatment after cell therapy.
It is essential to note the registry captures toxicity information differently than a clinical trial. The CIDR provides aggregate data to understand the expected toxicity of a therapy versus individual narratives.
By capturing the information in aggregate form, the number of cases that develop these toxicities and their severity are better assessed. In addition, this data can inform future therapy development with the goal of reducing the toxicities of next-generation cellular therapies.
Additionally, the field is evolving rapidly, and clinicians are adapting to these new therapies. As a result, new practice patterns emerge, which are then captured by the CIDR. For example, since the launch of the cellular therapy registry and the establishment of the CIDR, the treatment of CRS has evolved by physicians using anti-cytokine therapy at earlier stages.
Increasing patient access to cellular therapies
Understanding patterns of care in the real world is vital to assessing underrepresented populations. The CIDR captured over 5,000 recipients of CAR-T cells. Eighty percent of these cases represent commercial CAR-T cells. Evaluating the number of commercial CAR-T cells shipped to a center by the number of cases that the same center reported to the CIDR provides an assessment of the representativeness of the data.
According to the first two PASS, assessing axicabtagene-autoleucel for large cell lymphoma, and tisagenlecleucel for acute lymphoblastic leukemia, and diffuse large B-cell lymphoma, the capture rate by the CIDR is between 60–70% in the US. This representative sample of the population provides a good understanding of the demographics of populations receiving these therapies.
As these therapies become more widely available, barriers to access will start to appear. Analysis of different population subsets can demonstrate whether observed outcomes align with those expected for the population as a whole, further refining its use.
Enriching future cell therapy research and development
Just like the cell therapy field, cell therapy outcomes databases are in the early stages of development.
As the number of approved therapies grows and more patients receive cell therapies, the information collected and reported will continue to enrich future research, provide data to improve cell therapies’ toxicity profiles, and, most importantly, expand patient access to next-generation cell therapies.
Marcelo C. Pasquini, MD, MS, is a professor of Medicine at the Medical College of Wisconsin, senior scientific director at the CIBMTR, and the principal investigator of the CIDR. He oversees the cellular therapy registry, the PASS, and the cellular therapy studies for CIBMTR. For more information, visit http://www.bethematchbiotherapies.com.
Filed Under: Drug Discovery