In January ASCO declared CAR-T therapy the Advance of the Year due to the incredible impact and potential this immunotherapy has had on the oncology landscape. In many cases, patients who failed to respond to every other treatment option and were considered terminal have achieved full remission through CAR-T therapy, and several new CAR-T treatments are showing profound positive results in pivotal trials.

As we gear up for ASCO’s Annual Meeting June 1-5 in Chicago, we look forward to learning more about breakthroughs in this groundbreaking therapy area, as well as discussing the obstacles that stand in its way. 

How it works

Chimeric antigen receptor T-cell (CAR-T) therapy uses the patient’s own cells to attack their cancer. The therapy involves extracting the patient’s T-cells and genetically engineering them to produce Chimeric Antigen Receptors that can recognize and attack a specific antigen on tumor cells. Once the cells are infused back into the patient’s body, the altered T-cells seek out and kill the cancer cells that harbor the antigen, then remain in the patient’s blood ready to attack if the cancer returns. 

In 2017, the U.S. Food and Drug Administration (FDA) approved two CAR T-cell therapies. The first, from Novartis, showed an 83 percent overall remission rate among children and young adults with acute lymphoblastic leukemia. The second, from Kite, a Gilead Company, showed 72 percent of patients responded and 51 percent achieved complete remission in a pivotal trial of adults with diffuse large B-cell lymphoma. 

These approvals are likely to be followed by many more. Companies across the industry are researching new applications for CAR-T therapies in leukemia, lymphoma, and myeloma, as well as solid tumor cancers.

However all of this progress and optimism around future applications of CAR-T therapy is also creating obstacles. CAR-T therapy is a complex treatment that can take several weeks to complete, and requires strictly managed protocols for T-cell extraction and engineering, along with highly trained staff and state-of-the-art handling and tracking infrastructure. This has limited the number of sites that can host these trials, and called into question who will pay for the time and effort involved in these therapies.

Growing pains

There are currently just 60 US sites conducting CAR-T therapy trials and they are all located at large academic transplant centers.  These are the same sites that are certified for commercial administration of CAR-T therapies per websites for KYMRIAH and YESCARTA.   This creates two distinct problems:

1. Too many trials, too few sites: Sites are being over-burdened with requests to host new CAR-T therapy trials, which is leading to delays in start-up, creating competition for a limited pool of patients, and overtaxing the existing staff and resources at the sites.
2. Limited access. For patients who don’t live near a centrally located transplant center, accessing these trials can be prohibitive. And because the window of opportunity to participate in these trials is short – most patients may only have months to live -- patients have little time to relocate or wait for the next trial to start. These time constraints are further exacerbated by the time it takes to engineer the cells. Kite’s recently approved treatment boasts a median 17 day turnaround on cell manufacturing, however in other trials manufacturing can take several weeks to complete.

These problems have created a frustrating dichotomy where trial sponsors are fighting to recruit trial participants from limited patient pools, while patients who may be eager to participate in this groundbreaking research but aren’t located near sites and cannot easily relocate aren’t being considered.

Another major challenge is the price tag.  Novartis’ recently approve therapy runs $475,000, while Kite’s is $373,000, and CMS and insuracne companies have been slow to put in place reimbursement rules.

These obstacles will need to be addressed for CAR-T therapy to become a mainstream treatment option and for this important research to continue. To get there, we need to expand the number of clinical research sites that can handle these trials, including community based transplant centers. We also need to implement more innovative strategies for recruiting patients, and to scale up T-cell manufacturing services to support the growing need.

While we don’t have all of the answers, there are several potential solutions to streamline the CAR-T clinical research environment through Human Data Science. These include:

• Building a patient registry that would expand and expedite trial sponsors’ access to a broader patient population.
• Using Real World Data, including medical claims data, to identify new potential trial sites based on their access to patients, number of experts, and experience in related trial research.
• Leveraging advanced analytics and machine learning to examine diverse, relevant data sets as a more efficient tool to find patients, identify trial sites, and generate better trial results.
• Creating more robust referral networks that link local experts and CAR-T trial sites as a way to better educate practitioners about the benefits of trial participation and encourage them to share these opportunities with their patients.

Let’s talk at ASCO

How can Human Data Science accelerate CAR-T trials? What other opportunities are there to consider? We look forward to talking with our clients and peers at the ASCO meeting in June about how we can collaborate on these projects and what other strategies we can pursue to help them move this exciting field of CAR-T research forward.

More about Jeffrey Hodge

Jeff Hodge is Vice President of Development Solutions in Oncology Center of Excellence at IQVIA. Jeff joined Quintiles in 2010 as Executive Director, Customer Solutions Management Group. In 2012, he also held the role as Vice President, Clinical Strategy & Delivery in Oncology/Neurology.

Contributors:

• Barbara Somlo
  Ph.D., Principal with our Oncology RWI Center of Excellence. Dr.Somlo focuses is on applying Real World Data including medical claims and oncology EMR data to business application such as market sizing, patient journey analytics and physician targeting.
• Marie Given
  Principal in Oncology Real World Insights for IQVIA. Her current responsibilities include building custom solutions and business development for Oncology Clients looking to understand market opportunity, patient treatment progression and more, using Real-World Insights.