From referral to infusion: Accelerating the CAR-T process
Click Here to Manage Email Alerts
There are many frustrating aspects to a cancer diagnosis.
Perhaps the most challenging is the waiting required for everything from test results to diagnosis confirmation to treatment initiation.
Patients eligible for chimeric antigen receptor T-cell therapy typically have high-risk or advanced disease that requires timely treatment to achieve maximum benefits, according to Jason Westin, MD, MS, FACP, director of lymphoma clinical research and section chief for aggressive lymphoma at The University of Texas MD Anderson Cancer Center and chair of the Government Relations Committee for ASCO.
Despite a need for timely treatment, commercially available CAR-T products require patients to wait up to a month for manufacturing.
“Cell therapy, including CAR T cells, has been an incredible breakthrough for patients fighting lymphomas, myeloma and leukemias,” Westin told Healio. “However, a big risk for our patients is having to wait for treatment and letting their aggressive and treatment-refractory cancer get worse in the meantime.”
In this installment of In Practice, Westin explains what referring physicians can do to expedite the CAR-T process and enable optimal outcomes for their patients.
Healio: How significant of an issue are late referrals for CAR T-cell therapy?
Westin: It's a big issue, and it's something we struggle with at our clinic every week. A discussion about bridging therapy is required for most patients who receive CAR T-cell therapy, and about half the patients ultimately will receive it. That percentage goes up a lot if there is a delay referring patients with diffuse large B-cell lymphoma. The longer it takes to refer somebody, the more likely they will receive toxic bridging treatment and be at risk for not receiving CAR T cells. Therefore, the right time to refer patients would be as soon as an oncologist suspects they might need CAR T cells.
Healio: Do outcomes improve for patients who receive CAR T-cell therapies sooner?
Westin: Patients who receive CAR T cells generally have aggressive cancers, and most patients with lymphoma who receive them need some type of treatment relatively quickly. Time really matters, and days and weeks count for patients who are sick and have an aggressive malignancy that is progressing.
It doesn't matter whether we approach this from the angle of the line of therapy or the time to therapy. The longer it takes for a patient to receive their CAR T cells, the greater risk of death from cancer or bad outcomes.
A couple clinical trials have looked at the impact of time to infusion of the cell therapy product, and results have suggested that longer manufacturing wait periods can impact the success or failure of some treatments.
When it comes to earlier use of CAR-T for large B-cell lymphoma, three randomized trials have reported results on use as second-line therapy. Two of these three trials demonstrated that CAR T-cell therapy was dramatically better than high-dose chemotherapy and autologous stem cell transplant. Based on the results from one of these trials, the FDA has approved axicabtagene ciloleucel (Yescarta; Kite Pharma/Gilead Sciences) for use as a second line treatment for patients with early relapsing or refractory DLBCL.
Healio: What role does the insurance approval process have in treatment delays?
Westin: This is the first choke point in the process and a required first step, so referring physicians need to submit requests for approval as soon as possible. The impact of delays caused by the approval process has changed over time. A few years ago, when the FDA first approved CAR T cells, there were frequent delays. Most patients had to wait for a significant amount of time — at least a week. Now that we have had more experience — both among institutions that provide CAR T cells, as well as on the payer side — usually there is a way to move these through the process relatively quickly. But you can't count on expediency, and clinicians should expect that it could take a week or longer to receive a decision.
Healio: What additional delays need to be addressed?
Westin: Getting the appointment for apheresis is another choke point. This includes establishing the timeframe for collecting the patient's blood and then shipping it off for manufacturing. It's a twofold process. The first part involves getting your apheresis colleague to have the machine ready and the personnel available to draw and collect the patient's blood.
More importantly, however, is for the CAR T-cell company to have a manufacturing slot available. Some CAR T cells can be cryopreserved and basically put on hold, while others need to be fresh, and apheresis is not conducted until the appointment on the manufacturing side is available. Sometimes those appointments can be weeks out, or even up to a month away.
Reserving a patient’s manufacturing appointment is when the clock really starts. It is the vein-to-vein time of when the blood is drawn to when the product is returned that we consider as total manufacturing time.
Both of these factors can have a significant impact on the overall length of the CAR-T process.
Healio: Does the CAR-T product type have an impact on how long the process takes?
Westin: Yes, it does, and sometimes the anticipated vein-to-vein time is a way to differentiate which product should be used. If there is a patient who requires bridging therapy, then it may be more attractive to do apheresis immediately — before the additional treatment — and hold those cells in the freezer vs. waiting for a few weeks to do apheresis. Bridging therapy can potentially have consequences on the fitness of the T cells, so waiting is not just a risk for the patient, it increases the risk that the T cells become ineffective.
Healio: What can referring physicians do to accelerate the process for the patient and for the team at the CAR-T center?
Westin: First is early identification of patients who may be eligible for and benefit from CAR T cells. Referring physicians should not hesitate if they have a patient who may be at risk for relapse. Considering the use of CAR T cells should come early in a community-based oncologist's thought process.
For example, if a patient with large B-cell lymphoma calls the clinic and has developed a new mass or pain, anticipating that this could turn into a CAR-T referral should be explored at this time and not wait until after all the patient's tests are completed and they come into the clinic weeks later. Clinicians should have a high suspicion early on that their patient may need CAR T cells to help reduce the timeline.
Second, referring physicians must communicate effectively and early with the CAR-T center that will treat their patient. I would encourage the physician or someone on their staff to call the intake personnel or a physician they know at the CAR-T center and clearly communicate that they have a potential patient. This typically will raise alarm bells among the people at the CAR-T center to get the process moving quickly.
Opening communication with the CAR-T center quickly is especially important for higher-risk patients. Having this heads-up allows the center to ensure spots are available and will help them prioritize that patient to avoid any delays that may jeopardize their ability to receive the treatment.
Healio: Will the process become faster if more CAR T-cell therapies are approved?
Westin: Yes, I believe having more products approved will speed up the process. But a lot of patients need these therapies so, when a new product comes to market, the existing built-up demand overwhelms the additional supply. Although I think new products receiving approval would have many positive effects, the most important fix we need to expedite the CAR-T process is expanding the manufacturing capacity to make more of these cells. Because increasingly more patients are aware of and interested in cell therapies, the demand and supply must match up.
Healio: Will centers like yours be able to keep up with increased demand as more indications are approved? Could this become another choke point if manufacturing capacity is not expanded?
Westin: Increased demand is an issue but will be required for the growth of successful CAR-T programs. Large CAR-T centers like ours may struggle with the number of patients that can be treated, but we can handle that demand because it's a home-run therapy that we want to offer to our patients. Our job is to provide the best available therapies to the largest number of people we possibly can. Cell therapies are a wonderful example of what technology can do to lengthen and improve the lives of people who are living with cancer or even provide them with a potential cure.
The charge for cell therapy centers is to staff up and to grow their programs such that they are keeping up with that demand. I feel that centers like ours are doing that, but we need help on the manufacturing side to do their part.
Healio: In the future, do you expect the CAR-T process to become more timely?
Westin: I think it will become more expedient due to improved manufacturing processes. Everybody involved with CAR-T development is interested in providing therapies faster — whether that be from diagnosis to infusion, the vein-to-vein manufacturing time, or as an earlier line of therapy. There is huge pressure to provide these therapies in a more timely and effective fashion.
Some of the newer products still in research theoretically will be manufactured within a handful of days. There are CAR T cells in development that are designed to expand after infusion — meaning that the final product is not fully baked by the time it's given to the patient and the cells continue to develop once they are infused.
Then there is the promise of what are called off-the-shelf therapies — immediately available allogeneic products that are not produced for one patient but are manufactured to have multiple doses from a single donor. Hopefully, in the not-too-distant future, patients will be able to receive a cell therapy without waiting for apheresis and manufacturing. Instead, cell therapies will be like a drug that is available in the pharmacy — one the patient can receive at a cell therapy center or local infusion clinic. All of these advances in development will help us in the coming years to shorten the treatment process.
For more information:
Jason Westin, MD, can be reached at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.
Collapse
Healio Interview
Click Here to Manage Email Alerts