Know-How About New CAR-T Cell Therapies Shifting

Ingrid Hein

September 30, 2019

Chimeric antigen receptor (CAR) T-cell therapies for cancer are still so new and they can be extremely effective, but "it's a therapy that carries a lot of risk," said Lauren Spendley, NP, from the Dana-Farber Cancer Institute and Harvard Medical School in Boston.

At her center, she explained, all patients who have received CAR T-cell therapy are admitted for a minimum of 1 week after infusion. A rotating team of advanced practice providers take care of those and other hemo-malignancy patients.

"We realized that we needed a dedicated group to make sure we were able to safely provide quality care for these patients, given the unique toxicity profile" said Spendley, who described her experience as a CAR-T program manager and presented research on associated toxicities from two studies she was involved in (Brain. 2019;142:1334-1348 and J Adv Pract Oncol. 2019;10[suppl 3]:11-20).

Typically, the toxicity comes in two waves. "The onset of cytokine release syndrome [CRS] occurs 24 to 48 hours after the cells are infused. It can last about a week. It looks a lot like sepsis," she explained. "Then the neurotoxicity comes on day 5 or 6, and can last days to weeks," she said, noting that it usually overlaps CRS.

If patients have severe CRS, "we predict they'll have severe neurotoxicity as well," she added. And patients with a higher burden of disease tend to have higher-grade toxicities. "You can sort of see that coming."

These patients undergo an infection workup, and treatment with antibiotics and tocilizumab usually resolves the infusion reaction. "Having vigilant advanced care at the bedside plays a role in identifying and treating symptoms," Spendley explained. Both CRS and neurotoxicity can be fatal when not treated quickly.

Before CAR T-cell treatment is administered, patients are assessed for comorbidities, performance status, and organ function. "They need to be able to tolerate these toxicities if they become severe," she noted.

But the results of CAR T-cell therapy are nothing short of amazing, she emphasized at the Association of Physician Assistants in Oncology 2019 Annual Symposium in Boston. "That someone suffering so much from their disease can, days to weeks later, be in complete remission is remarkable. It's truly ground-breaking for the lymphoma landscape."

Demand on the Rise

The Centers for Medicare and Medicaid Services recently announced that the costly therapy would be covered for indications approved by the US Food and Drug Administration — along with some off-label uses — in hospitals that participate in the Risk Evaluation and Mitigation Strategy (REMS) program, as reported by Medscape Medical News.

For children with acute lymphoblastic leukemia, the therapy costs $475,000; for adults with diffuse large B-cell lymphoma, it costs $373,000. Until now, this was out of reach for patients without insurance or other means to foot the bill.

But care teams need to be ready for increased demand. Centers offering the therapy will benefit from a dedicated team, Spendley asserted. "At our center, we can now accommodate a larger volume of patients without missing a beat because we are prepared with the knowledge and experience to know the signs of complications," she said.

The treatment can be highly effective, "making the tumor disappear within days," said Kadee Raser, PA-C, CAR T-cell therapy lead at the University of Michigan Rogel Cancer Center in Ann Arbor.

She described a patient with a tumor on the side of her neck: "Just days after the CAR T-cell therapy, you visibly saw the area shrink dramatically and go away. You don't typically ever see that with standard-therapy radiation."

These patients can end up in the ICU. It's different than your typical transplant or chemo.

However, the toxic effects of the therapy "can get complicated," Raser told Medscape Medical News. These patients "can end up in the ICU. It's different than your typical transplant or chemo."

"We watch these patients very closely," she added.

The Rogel Cancer Center did its first CAR T-cell infusions when the treatment was in its infancy and then developed a dedicated program.

"It helps that our advanced providers were involved from the beginning," said Adrienne Trentacosti, PA-C, outpatient CAR T-cell therapy lead at Rogel. "We have a rapidly growing team of nurse practitioners and physician assistants with CAR-T knowledge who work interchangeably to manage patients."

A physician always performs the preliminary patient consult, Trentacosti said, but once the patient is deemed suitable in a team meeting, advanced practitioners — including nurse practitioners and physician assistants — set up the therapy and follow the patient through to recovery.

"We're the continuity, the glue, that holds the treatment together, and the daily connection to the patient," she said. That makes it easier to identify any change in the patient. "Assistant practitioners don't rotate; we're always there. Physicians move from inpatient to research to something else."

"We spend more time with the patient than the physicians or nurses are able to," she added.

As the general population ages, oncology will continue to be a growing field for physician assistants. "We're going to see more oncology patients," Trentacosti noted.

Because "the cellular therapy program is fairly new, we're just now hiring dedicated staff, dedicated social workers, and dedicated physician assistants for CAR T-cell therapy," she added. "We're expanding rapidly. I just hired four new people."

There is a lot of interest and excitement about the therapy, Raser confirmed, but she warned that the final results are not in yet. "We're a little early in speaking to the durability of the treatment." she said. "We don't know how long it lasts. We are still learning."

Spendley, Raser, and Trentacosti have disclosed no relevant financial relationships.

Association of Physician Assistants in Oncology (APAO) 2019 Annual Symposium.

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