CAR T-cell therapy could be effective for brain cancer

In CAR T-cell therapy,  white blood cells called T cells are removed from a patient's blood before being genetically modified to make proteins called chimeric antigen receptors (CAR). These receptors allow T cells to target and destroy cancer cells. The genetically modified T cells are then infused back into a patient's blood.

So far, FDA has only approved CAR T-cell therapies to treat blood cancers, including several types of leukemia and lymphoma and multiple myeloma, but early data suggests that it may also be effective against other types of cancer.

For example, findings from two separate studies suggest that CAR T-cell therapy could be used to treat glioblastoma multiforme (GBM), an aggressive and incurable type of brain cancer. After being diagnosed with GBM, patients have a median survival time of 15 months.

In the first study, which was published in the New England Journal of Medicine, researchers at Massachusetts General Hospital tested the treatment on three patients, with two being in their 70s and the other being in her late 50s.

The CAR T-cells used in the study were designed to identify and attack proteins called epidermal growth factor receptors (EGFRs), as well as a variant of (EGFRs) that are often found in GBM tumors but not in healthy brain tissue. All three patients in the study saw their tumors shrink after treatment. In the 57-year-old patient, an MRI taken five days after the infusion showed that her tumor was nearly gone.

"That's really sort of unprecedented," said Marcela Maus, the study's senior author. "As far as I know, there's really not any other drugs that do anything like that in glioblastoma."

In the second study, which was published in Nature Medicine, researchers from the University of Pennsylvania tested their own CAR T-cell therapy in six patients. Like the first study, the CAR T-cells targeted EGFRs, but the second target was another protein called IL13Rα2, which is found in 75% of GBM tumors.

All six patients in the study saw their tumors shrink in size after the first two days of treatment. They also had a significant spike in active CAR T-cells in their spinal fluid for several weeks after the treatment.

Although both studies found that CAR T-cell therapy could reduce tumor size, many of the patients saw their tumors grow again. A few patients have had longer-lasting responses, but it's not clear whether this will continue in the long-term.

Currently, both teams plan to continue their research into CAR T-cell therapy and modify their approaches to determine the best combination of treatments for GBM, including radiation and chemotherapy or potentially cancer-fighting vaccines.

"We're learning from each other. I think that's really a tremendous model, and what we are all seeing is that this sort of therapy has legs for brain tumor patients," Maus said. "It may not be the final version yet, but we're onto something."

Safety concerns about CAR T-cell therapy grow

CAR T-cell therapies have been shown to be an effective treatment for certain cancers, but there have been recent concerns about their potential safety risks.

Last November, FDA investigated whether CAR T-cell therapy could cause lymphoma, a blood cancer, following reports of CAR-associated T cell malignancies. In January, the agency sent letters to five companies that manufacture the treatment — Bristol-Myers Squibb, Juno Therapeutics, Janssen Biotech, Novartis, and Kite Pharma — requiring them to warn patients that "mature T-cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes."

Now, FDA staff are raising concerns about an increased risk of early death for patients being treated with two CAR T-cell therapies for multiple myeloma. One treatment is Janssen Biotech's Carvykti, and the other is Bristol-Myers Squibb's Abecma.

In trials for both treatments, more patients who were treated with CAR T-cells died in the early months of follow-up than those who received standard care. Although this trend reversed over the course of the trials, the information was enough to raise FDA's alarm.

On Friday, the Oncologic Drugs Advisory Committee met to evaluate whether the benefits of expanding CAR T-cell therapies to earlier stages of cancer outweigh the potential risks of harm. The group voted 11-0 and 8-3 that the benefits of Catvykti and Abecma outweighed their risks, respectively. FDA is not bound by the advisory committee's decisions, but usually follows its recommendations, according to MedPage Today. (Herper/Mast, STAT+ [subscription required], 3/13; Sullivan, NBC News, 3/13; Ledford, Nature, 3/13; Goodman, CNN, 3/13; Reed, Axios, 3/15; Bankhead, MedPage Today, 3/14; Garde, STAT, 3/14)

How leaders should approach CAR T-cell therapies amid safety concerns

By Chloe Bakst and Rachael Peroutky 

Many health system leaders are keen to transition CAR T-cell therapy delivery to outpatient care, but they are faced with mounting tension between the therapies' effectiveness in treating rare, deadly conditions and their potential safety risks.

By transitioning CAR T-cell therapy delivery to outpatient care, health systems can free inpatient beds, collect better reimbursement, and improve patient experience in some cases. However, outpatient delivery will introduce new challenges and may exacerbate existing ones, including patient safety concerns.

How leaders should be thinking about CAR T-cell therapy delivery

For outpatient delivery to work, caregivers will have to take on more responsibility in post-treatment care. In addition, packed outpatient infusion sites may have to extend their hours of operation and ready staff for higher acuity patients. Clinician teams will also need to prepare for the unplanned readmission of patients experiencing adverse events.

Providers can invest in ways to deliver CAR T-cell therapy in the outpatient setting when appropriate, but inpatient programs will need to scale as well. Much of this work depends on internal infrastructure and coordination. Leaders should evaluate whether their teams are properly staffed and educated on treatment options and whether the right standard operating procedures are in place.

When working with innovative therapies, the patient journey is complex and often moves between several sites of care. Inpatient and outpatient providers need to create workflows that accommodate and ease that transition. 

No provider would argue that every cell and gene therapy is a good candidate for outpatient delivery. The decision is often made on a drug-by-drug, patient-by-patient basis. Still, the overwhelming interest in outpatient CAR T-cell therapy delivery signals that leaders need to be wary of putting their sole strategic focus on this model. Doing so could put their program at risk as the cell and gene therapy pipeline matures and more drugs hit the market.

With several FDA-approved CAR T-cell therapies on the market, a growing development pipeline, and CMS's initial steps to remove reimbursement barriers, many cancer programs are considering investing in CAR T-cell therapy for their patients.

Use our data-driven tool to estimate current and future demand for CAR T-cell therapy among cancer patients in your market.