The Price of Hope: Weighing the Cost of CAR-T Cell Therapy in Treating Blood Cancers

September 23, 2020

Weighing the cost of CAR-T cell therapy in treating blood cancers is a finical burden for many patients with blood cancer.

It’s been nearly a decade since Robyn Stacy-Humphries, a 58-year-old radiologist from Charlotte, North Carolina, first learned she had diffuse large B-cell lymphoma (DLBCL). Today, she’s in remission — a fact she attributes to her treatment with chimeric antigen receptor (CAR)-T cell therapy.

Through the years, Stacy-Humphries’ treatment has included everything from six cycles of R-CHOP chemo/biotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone and Rituxan [rituximab]) — the standard of care for DLBCL — to R-ICE (Rituxan, ifosfamide, carboplatin and etoposide), intrathecal chemotherapy (chemotherapy injected into the spinal fluid), myeloablative chemotherapy, high-dose BEAM chemotherapy (carmustine, etoposide, cytarabine and melphalan), rescued with an autologous stem cell transplant (a transplant using her own stem cells), and head and neck radiation. Although she’d gone into remission prior to her stem cell transplant, the cancer returned.

In April 2016, nine months after her stem cell transplant, Stacy-Humphries’ DLBCL returned again. With no matched donor on the horizon for an allogeneic transplant (a transplant using donor stem cells) — the next standard treatment for her cancer — she knew she was running out of time.

That’s when she and her husband got to work, researching clinical trials for an emerging treatment known as CAR-T cell therapy. She landed a spot in the phase 2 JULIET trial of Kymriah (tisagenlecleucel), a CAR therapy made by Novartis, at The Ohio State University’s Comprehensive Cancer Center.

“My early-phase clinical trial was like jumping out of a plane and hoping the parachute opens,” Stacy-Humphries says.

“I was one of the first 200 people in the world to receive this treatment. And the trial I was in was the basis for the FDA approval of the CAR-T cell product.”

Four years after receiving CAR-T cell therapy, she remains in remission and optimistic. “I’m likely to stay in complete remission,” she says. “But no one will actually give you a guarantee.”

What is CAR-T Cell Therapy?

CAR-T cell therapy is an immunotherapy, a type of therapy that helps a patient’s own immune system fight their cancer. Doctors draw blood from the person with cancer. The person’s T cells, white blood cells that develop from stem cells and help fight infection, are then separated from the blood in a laboratory that makes the CAR-T cell product. There, scientists change the genetic make-up of the T cells, making them produce customized receptors called chimeric antigen receptors that recognize specific proteins on tumor cells. These engineered T cells are then grown, or expanded, in the lab.

Once the CAR-T cell product has expanded, the person with cancer receives chemotherapy known as lymphodepleting treatment. This treatment clears the way in the body for an infusion of the re-engineered T cells, which multiply further in the patient’s body. The CARs then help the person’s T cells find a certain protein, known as an antigen, on the surface of cancer cells and destroy the cancer.

In 2017, the Food and Drug Administration (FDA) approved two types of CAR-T cell therapies. Kymriah was approved for patients up to age 25 with B-cell precursor acute lymphoblastic leukemia (ALL) who relapsed after two or more treatments, while Yescarta (axicabtagene ciloleucel) was approved for adult patients with large B-cell lymphoma who have relapsed after, or not responded to, two types of treatment.

In 2018, the FDA also approved Kymriah for adults with large B-cell lymphoma, including DLBCL, who have relapsed after or not responded to two or more standard therapies. In July 2020, the FDA approved Tecartus (brexucabtagene autoleucel) for adults with mantle cell lymphoma who have not responded to other treatments or relapsed after those treatments.

According to Dr. Frederick Locke, a medical oncologist and translational researcher in the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center in Tampa, Florida, which was part of the clinical trial that supported the approval of Tecartus, having CAR-T cell therapy as an option for patients with mantle cell lymphoma is critically important.

“We have therapies for relapsed refractory mantle cell lymphoma that can work, but when patients relapse after getting those treatments, the disease can progress very rapidly,” he says.

CAR-T cell therapy offers hope for some patients with certain blood cancers who have not responded to conventional therapies, Locke adds.

“When we look at outcomes in patients with refractory diffuse large B-cell lymphoma, we know from robust historical data that patients who didn’t respond to their last line of chemotherapy or relapsed after an autologous stem cell transplant have a very low chance of responding to more therapy — conventional therapy, that is,” he says, adding that about 1 in 4 patients can expect to respond to another line of chemotherapy and less than 1 in 10 can expect their lymphoma to disappear after additional conventional therapy.

“These are the same patients who are now eligible for CAR-T cell therapy and the results are remarkable,” he says.

Locke adds that 30% to 40% of patients with DLBCL who have CAR-T cell therapy achieve durable remission that stretches beyond three years and counting. “These are results we would not expect and would not have seen with existing therapies for refractory diffuse large B-cell lymphoma,” he says, noting that data from randomized controlled clinical trials on the long-term impact of CAR-T cell therapy are still needed.

Considering Cost

CAR-T cell therapy is complicated; it’s also potentially expensive for those who qualify for treatment. In a July 2020 comment on the Centers for Medicare & Medicaid Services (CMS) Hospital Inpatient Prospective Payment System proposed rule, the American Society of Clinical Oncology noted the average cost of a CAR-T cell product at $373,000, with the estimated cost of CAR-T cell therapy and related services at $419,238.

Medicare covers a portion of CAR-T cell therapy provided in health care facilities that are enrolled in FDA risk evaluation and mitigation strategies (REMS), a federal program that oversees the safe use of drugs, for FDA-approved uses. Medicare may also cover a portion

of some off-label uses of CAR-T cell therapy that meet certain recommendations. While private health insurance plans may cover some or all of the cost of the product for patients who qualify for FDA-approved treatment, there are additional costs related to CAR-T cell therapy for which patients might bear a heavy financial burden.

These additional costs include a pre-therapy consult, chemotherapy to deplete the lymphocytes, and collection procedures, as well as expenses during recovery and ongoing monitoring according to Dr. Stuart Goldberg, chief of the Division of Outcomes and Value Research at the John Theurer Cancer Center at Hackensack University Medical Center in Hackensack, New Jersey.

“It also involves doctor visits, two weeks in the hospital, post-procedure care, all of the X-rays, CT scans, etc.,” he says. “None of that is the $400,000 cost of the CAR T. And CAR-T cells aren’t available in your backyard. So, you’re talking about hotel rooms, transportation, time off work for loved ones and caregivers. There are other costs that sneak in that no one talks about.”

Goldberg wants to change that.

“Everybody thinks that cancer patients are most worried about pain,” he says. “It turns out that more cancer patients are worried about the cost of care. When patients come in to see us, we ask about side effects like fever, pain and nausea. But most times when we see a patient, we rarely talk to them about whether they can pay the bills.”

According to Goldberg, patients who go through expensive treatments such as bone marrow transplant or CAR-T cell therapy talk to a financial counselor as part of the consult. “They map out what the out-of-pocket costs might be, and what costs their insurance might cover,” he says. “If we identify someone who we think may have some difficulty, we start to plug them in to various support programs that might be available. But even then, we cannot anticipate all the costs of travel, hotels, lost wages and other non-medical expenses that could burden the patient and their family.”

Stacy-Humphries says it’s important to keep costs — and outcomes — in perspective when evaluating treatment options. While much of her CAR-T cell cost was covered as part of her clinical trial, she had to pay out-of-pocket costs for all of the tests required to get into the trial before she met her insurance’s high deductible, she says. “But those were the same tests that would be required to have an allogeneic transplant,” she says, noting that her own research puts the cost of an allogeneic transplant, over time, at about $800,000. “And it’s not like chemotherapy is free. It’s very expensive.”

Dr. David Siegel, chief of the Myeloma Division at the John Theurer Cancer Center at Hackensack University Medical Center, says the standard of care for multiple myeloma, a four-drug combination given to newly diagnosed patients with the intention of administering it indefinitely in the absence of progression, is incredibly expensive.

“The cost of these drugs is tens of thousands of dollars a month,” he says. “If you’re a lucky patient and you stay in remission for three or four years, which is certainly not out of the realm of what’s expected, it’s $300,000 a year to give these drugs.” The cost of CAR-T cell therapy, which is not yet FDA approved for myeloma treatment, seems relatively inexpensive by comparison if a patient then doesn’t need to be treated for two years, he adds.

Treating potential side effects of CAR-T cell therapy may add additional costs. Some patients develop cytokine release syndrome, an immune system response that causes high fever and low blood pressure, or neurotoxicity, brain impacts such as seizures or confusion. Although these medical toxicities can usually be controlled, the additional treatments may add to the “financial toxicity.”

Finding Support

Some nonprofit organizations offer assistance for eligible patients — or can help connect patients to programs that help with paying for care, travel and lodging. The Leukemia & Lymphoma Society (lls.org) offers a co-pay assistance program for eligible patients, while CancerCare (cancercare.org) offers travel and other assistance for eligible patients.

Pharmaceutical companies may also offer patient assistance programs; for example, Novartis offers Kymriah Cares. According to Julie Masow, global head of Novartis Oncology External Communications in Cambridge, Massachusetts, assistance and support for eligible patients may include benefit and network investigation, co-pay assistance and travel support. Patients seeking help with private insurance to help cover their portion of financial responsibility for Kymriah should speak to their doctor or treatment center about eligibility and submitting a request for co-pay assistance.

Patients participating in clinical trials find that many CAR-T cell therapy expenses are covered. Chrissy Degennaro, 50, of Ocean City, New Jersey, was 36 when she received a multiple myeloma diagnosis. She has participated in two CAR-T cell clinical trials — one in 2017 and one in 2018 — with Celgene, now a Bristol Myers Squibb company.

During the first trial, when her engineered T cells were infused, Degennaro spent two weeks in the hospital, followed by two weeks in a hotel nearby. A bone marrow biopsy two weeks after completing treatment showed no signs of myeloma, she says.

Her treatment and hotel costs were covered during the trial, she says.

“Participating in the study made it affordable,” Degennaro says. “It wasn’t the financial burden on me that it could have been.”

A year later, her myeloma returned, so she had a second CAR-T cell treatment and was in remission for a few months. Her myeloma has since returned.

“To have even six months off treatment is a treat,” Degennaro says, adding that today, she takes a combination of selinexor, Velcade (bortezomib) and dexamethasone. “Some people say CAR T is not worth it. It was totally worth it for me. It gave me all that time off treatment.”


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