ORLANDO, Florida — Chimeric antigen receptor (CAR) T-cell therapy has been hailed as a major advance and a game changer, but their cost has redefined the meaning of "expensive."

Karl M. Kilgore, PhD

However, new "real-world" data now suggests that CAR-T cell therapy may actually be cost effective, as it may lower other expenses related to the illness.

When used in a population of older adults with non-Hodgkin's lymphoma, these new data show that CAR-T cell therapy cut related expenditures compared with healthcare costs prior to receiving this treatment.

"CAR-T therapy was associated with fewer hospitalizations, shorter time in the hospital, fewer ED visits, and lower total healthcare costs," said lead study author Karl M. Kilgore, PhD, of Avalere Health in Washington, DC.

He presented the findings here at the 2019 annual meeting of the American Society of Hematology (abstract 793).

CAR-T cell therapies were approved in the United States in 2017. First came tisagenlecleucel (Kymriah, Novartis), for the treatment of pediatric and young adult patients with acute lymphoblastic leukemia, with a price tag of $475,000. Closely following it was axicabtagene ciloleucel (Yescarta, Kite/Gliead), indicated for adult patients with relapsed/refractory aggressive B-cell non-Hodgkin's lymphoma who are ineligible for autologous stem cell transplant, with a price tag of $373,000.

The formidable price tags sent shock waves through the blood cancers community, which is struggling to incorporate this novel approach because of the remarkable responses that have been seen.

Real-World Experience

In the current study, Kilgore and colleagues evaluated the demographic and clinical characteristics of Medicare patients who received CAR-T therapy (axicabtagene ciloleucel or tisagenlecleucel) and then compared healthcare utilization, costs, and outcomes pre- and post-CAR T therapy.

"The goal of this study was to look at the real use of CAR-T cell therapy and real-world data on the use of these therapies," said Kilgore. "And to look at healthcare utilization."

Data was obtained from the Centers for Medicare & Medicaid Services 100% Medicare Fee-for-Service Part A and B claims data, and patients were included in the study if they had been diagnosed with lymphoma and received CAR T therapy between October 1, 2017, and September 30, 2018.

A total of 177 patients met all of the inclusion criteria and were included in the analysis.

The average age was 70 years, more than half (58.8%) were male, and they were primarily white (87.6%). Nearly all patients (91.5%) had a primary diagnosis of diffuse large B-cell lymphoma (DLBCL), as well as multiple co-morbidities with 74.6% having a Charlson Comorbidity Index score ≥ 3. Fewer than 5% of patients had undergone a previous autologous stem cell transplant, and 51% had one or more comorbidities that would have disqualified them from participating in CAR-T clinical trials (eg, renal failure, heart failure, recent history of DVT/PE).

Just over half of participants (52%) had been treated with intravenous chemotherapy in the 6 months prior to receiving CAR-T cell therapy, and 60% received outpatient lymphodepletion.

During their index episode of care for CAR-T infusion, the patients spent a median of 16 days (interquartile range, 10) in the hospital during and 45.5% required ICU care after infusion. In the 6-month period prior to CAR-T cell therapy (pre-index), 51.2% had been hospitalized at least once, and almost 20% had three or more periods of hospitalization. Of that group, 27.1% were readmitted during the post-index period.

Among patients who required hospitalization, the median length of stay pre-index was 7 days and 5 days post-index. The number of ED visits was also lower in the post- vs pre-index (15.8% vs 29.9%).

"Patients spent 17% less time in the hospital 6 months after CAR-T cell therapy than before," he said.

While there were no deaths during the post-index period, a small percentage (< 5%) were admitted to hospice care. It is unclear if any patients received chemotherapy during the 100-day post-index period, which would suggest disease progression. However, the authors note that claims for the period might be lagging behind for some patients.

Kilgore pointed out that half of the patients had one or more chronic conditions that, in some cases, would have excluded them from clinical trials. "But 73% remain alive at 6 months," he said. "We have data that goes out to 21 months, and over 50% are still alive at almost 2 years."

As for cost, the median total healthcare costs during the pre-index period were $51,999 (mean, 58,820; standard deviation [SD], 45,701) and $14,014 post-index (mean, 23,738; SD, 29,698). This extrapolates into $9,749 pre- vs $7,121 post-index for each patient per month, which is a 27% decrease in expenditures.

Kilgore explained that the total paid amounts for CAR-T from all sources (Medicare and patient) varied significantly, depending on whether patients were treated in a clinical trial and whether the hospital was reimbursed under standard Medicare prospective payment system (PPS) for inpatient facilities or through the PPS-exempt payment system.

Impressive Survival

Commenting on the study, Sarah Rutherford, MD, a hematologist at Weill Cornell Medicine and New York-Presbyterian in New York City, believes that the key takeaway from this study is that the majority of participants — who were older and sicker than many enrolled on CAR T-cell clinical trials — did quite well.

"Diffuse large B-cell lymphoma is a disease that usually causes people to die quickly if they are refractory to multiple lines of therapy, so the 6-month survival of 75% in this patient population is impressive," she said. "A large proportion of these patients are likely to have died had they not received CAR T-cell therapy."

Rutherford noted that the study authors analyzed the costs associated with patients in the pre- and post-CAR T-cell setting, finding that healthcare costs were lower following CAR T-cell therapy in this Medicare patient subset compared with costs prior to the therapy.

"I think CAR T-cell use is certainly justified given the lack of efficacious therapies in relapsed and refractory DLBCL patients, and this study indicates that there may be a financial benefit as well, though the actual costs associated with CAR T-cell therapy were not included in the analysis," she told Medscape Medical News.

Also weighing in on the study, James Essell, MD, from the US Oncology Network, pointed out that CAR-T cell therapy is changing the paradigm of treatment. For example, refractory lymphoma has a life expectancy of about 6 months. "But with newer data we're seeing about 50% of patients alive at 3 years after CAR-T cell therapy and we're thinking that will equate into a cure," he said.

Essell explained that In the past, the scenario would be 6 months of chemotherapy, relapse, other chemotherapy, relapse, and then CAR-T, but several clinical trials are now looking at giving CAR-T at first relapse. "Instead of waiting until they've had a transplant, which is going to be about $100,000 at least, they are going to be randomized between autologous transplant and CAR-T up front," he said.

"We are also doing clinical trials through the network for patients who are not candidates for an autologous transplant," Essell continued. "They will go straight to CAR-T therapy and that will really increase the cure rate because these are people who weren't eligible for any curative therapy — and now they are being given a chance."

Whether CAR-T cell use will expand to broader populations will depend on the results of the randomized trials that are ongoing now, he added.

"That's our hypotheses right now, but they are being studied in a wide range of hematological cancers, and in addition, there is a lot of research in solid tumors," Essell said. "I don't think you'd see this mass amount of research and dollars being poured into it if people didn't think it was going to be a game changer."

Kilgore has disclosed research funding from Kite Pharma. Several of the other co-authors have disclosed relationships with industry, which are noted in the abstract. Essell has disclosed no relevant financial relationships.

2019 Annual Meeting of the American Society of Hematology: Abstract 793. Presented December 9, 2019.

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