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June 3, 2022

'How do you decide?': The CAR-T cell shortage is forcing impossible decisions

Daily Briefing

    Although CAR-T cell therapy is a promising treatment for many cancer patients, supply shortages and limited manufacturing capacity mean many eligible patients spend months on waiting lists—and around 20% die before they can receive the treatment, Angus Chen writes for STAT News.

    What is CAR-T cell therapy?

    In CAR-T cell therapy, providers remove a type of immune cell called T cells from a patient's blood, genetically modify them with receptors that target and destroy cancer cells, and then infuse the T cells back into the patient's blood.

    These therapies are promising treatments for certain cancers, particularly blood cancers. For example, a study of three patients with chronic lymphocytic leukemia who received CAR-T therapy as part of a clinical trial in 2010 found that two of the patients went into remission within a year of the initial treatment and remained cancer-free for the next ten years.

    However, CAR-T cell therapy does pose serious side effects—including cytokine release syndrome, neurological effects, high fevers, comas, dangerously low blood pressure, and even death. That said, these symptoms have dissipated in most patients.

    So far, FDA has approved CAR-T cell therapies to treat several types of leukemia and lymphoma, as well as multiple myeloma, and CAR-T clinical trials are ongoing for a range of other cancers.

    Long wait times limit access to CAR-T cells

    Although CAR-T cell therapies have shown great efficacy for many patients, access to the treatment has been largely limited due to relatively few manufacturing slots, as well as an extensive manufacturing process.

    Currently, there are only around 70 cancer centers in the United States that can prescribe CAR-T cell therapy for their patients. And although there may be dozens of eligible patients, there are much fewer manufacturing slots available to create the therapy, which must be manufactured individually in specialized labs. A shortage of raw materials and supply chain restraints have also made it harder to manufacture CAR-T cells.

    "The median is 1 to 2 slots per month," said Yi Lin, medical director of the cellular therapy program at Mayo Clinic. "It ranges from 0 to 4 per center, and some cancer centers get no slots." She added that clinicians "have to pick off a list of close to 100 patients to get these slots."

    Because of this, many eligible patients end up spending months waiting for slots to open up. "And people are dying—about 20% of all our patients together are actually dying before they can get CAR-T" said Krina Patel, director of the myeloma cell therapy program at MD Anderson Cancer Center.

    "That's the hardest part," Lin said. "How do you pick the patient that you think their disease is not going to progress quickly enough that they get too sick to get the treatment and are still healthy enough in the next few months to get to the CAR-T dosing? How do you decide?"

    According to Chen, there are currently no national guidelines to assist clinicians in choosing which patients should get the treatment, meaning many must try "to balance between advocating for their sickest patients and those who might be most likely to benefit" on their own.

    After patients are selected for CAR-T cell therapy, they must also wait out the "vein-to-vein time" between T cell collection and infusion, Chen writes. In a best-case scenario, the process will take roughly three weeks to complete, from patient evaluation to manufacturing to infusion.

    However, many myeloma clinicians say the average vein-to-vein time for CAR-T cells is usually around five to eight weeks due to manufacturing delays and other potential problems. In addition, "[i]f something happens to the patient while their CAR-T cells are being made, that slot's used up — and the cells may be wasted," Chen writes.

    "Within days, after collection, the patient got really weak, tired, didn't look right. The disease just took off. We did everything to keep this patient's disease under control — and he died before he could get the CAR-T," Lin said, recounting an experience with one of her myeloma patients. "That one hit us really hard. We didn't think he would progress that rapidly. It felt like we failed that patient, and maybe that slot would have helped another. It's heartbreaking."

    How companies are trying to improve the CAR-T cell process

    According to companies that produce CAR-T cell products, including Novartis, Bristol Myers Squibb, and Janssen, the industry is rapidly increasing its capacity to manufacture CAR-T cells and working to shorten patients' vein-to-vein time.

    Currently, many facilities manufacture CAR-T cell products by hand, but companies are planning to automate some steps and test new technologies to help expedite the process. In addition, some companies have built digital platforms for their CAR-T cell processes, and they are being integrated into both new and existing facilities.

    According to Kwok Pang, an executive at the cell and gene therapy company Autolomous, digital systems will reduce the risk of errors. In addition, being able to share records electronically across all stakeholders, including hospitals, shippers, and drugmakers, could potentially make the manufacturing process 40% faster.

    Although Patel said she is not sure when the current CAR-T cell shortage will end, she is optimistic that new technologies will help shorten the time patients are left waiting for the treatment.

    "How do we get enough slots for everyone if we can't do it now?" she said. "There's hope that people can manufacture CAR-T in two days — making it easier, faster, so you're not waiting around for bad things to happen. The field is moving towards efficiency." (Chen, STAT News, 6/2)

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