Real-World Data Offer Good News for CAR T-Cell Therapy

When the first chimeric antigen receptor (CAR) T-cell therapy was approved in August 2017, the headlines spoke of the miracle it offered for some patients with incurable forms of leukemia. But most stories let the other shoe drop: the price tag for the first treatment was $475,000. And that was just for the treatment itself, before any hospital costs were added.

On its face, it might seem ridiculous that a cancer treatment costs more than most homes in the United States. But then health care analysts waited for the data to come in. And it turns out that when one compares the total, real-world costs of CAR T-cell therapy with its alternatives, including autologous or allogenic hematopoietic cell transplants (HCT), the newer technology compares pretty well.

An abstract presented recently at the American Society of Hematology examined costs during the period 6 months before and after these procedures, and compared CAR T head to head with transplants. Researchers from Avalere Health included data from matched pairs of 175 patients each for the comparison of CAR T-cell therapy to autologous HCT, and 142 patients each for the allogenic HCT comparison. All cohorts had a median age of 69-70 years, with mostly white and mostly female. Of the group, only 10% to 15% were dual eligible. Patients in the autologous HCT group had slightly more comorbidities on average than the allogenic HCT group.¹

The analysis by Avalere Health made the following comparisons:

• Mean medical costs of autologous HCT were higher than CAR T by 35% ($85,382 vs $63,081) during period prior to the procedure. Post-procedure cost slightly favored auto HCT, but by a smaller amount ($25,277 vs $33,876).
• In the allogenic HCT comparison, transplant mean costs were higher prior to the procedure ($92,119 vs $70,105) except emergency department visits. However, post-procedure costs were substantially higher for the allot HCT procedure compared with CAR T ($82,847 vs $34,477).

The American Journal of Managed Care® (AJMC®) asked Karl Kilgore, PhD, a senior research scientist at Avalere Health, to discuss the real-world data gleaned from Medicare fee-for-service (FFS) Part A and B claims. The data set go back to the beginning of CAR T-cell therapy administration in Medicare FFS, so AJMC® asked Kilgore: Could the data confirm the anecdotal reports that clinicians are getting better at CAR T-cell administration? Could the numbers tell us that costs are coming down?

The short answer: not yet. Kilgore explained that because this year’s abstract was a follow-up of one presented in 2019 (with a much smaller number of patients), Avalere didn’t alter how it evaluated the costs. But the question of how costs are changing over time is one that payers and others want to know.

“It's definitely a focus on the Avalere side. We are designing studies … to try to address those very questions,” Kilgore said. “We are hearing exactly the same thing.”

Below are excerpts from the AJMC® interview with Kilgore, edited for clarity:

AJMC®: How do real-world data on chimeric antigen receptor (CAR) T-cell therapy presented last year at ASH compare with updated data you presented this year?

Either in terms of the utilization or the costs, you may recall the CAR T sample that we used a year ago at [the American Society of Hematology annual meeting] was literally the first year of real-world CAR T experience. And we used the Medicare fee-for-service database the same as we used the claims database, same as we used for this study here.

More data [are] becoming available rapidly, both in terms of the frequency of CAR T occurring and it appearing in our data assets that we have. This study, however, because of the design, we decided it was best to stay with our initial CAR T sample.

So, the CAR T sample is still that original sample of a little over 200 patients that represent the initial CAR T experience. Then we took our other samples for the same time period to make them comparable in terms of the timing. … The number of CAR T events that we are seeing in our data is doubling about every 6 months. And if we were to do this study again now with fresh data, we would probably have 1000 patients that we could use and be able to trend that over time. One of the limitations of the earlier study was we didn't have any [Medicare] Part D data, prescription drug data, at all. Now we do, all the way up through 2019. And so, while I unfortunately don't have any trend data on cost for utilization to share, it's definitely a focus on the Avalere side. We are designing studies, talking to our clients just to try to address those very questions, because our clients and we are hearing exactly the same thing.

Costs are going down, adverse events are going down. We're having those discussions, and I can't wait to get my hands on some data that I can share with the community that quantify what people are observing, kind of idiosyncratically.

AJMC®: Basically, as clinicians get better at the administration of a very new technology, the outliers will get reined in, and health systems will get better get better at predicting who should get CAR T in the first place.

Kilgore: I think that's true. And think of [intensive care unit] stays, per se. We know from this study, for example, that ICU stays are slightly more likely in the CAR T patient than in the stem cell transplant patient. Although the length of stay in the ICU tends to be longer for the transplant and for the CAR T patient, we know from our discussions with clinicians, and from their own experience that they're seeing as time goes on, is that patients are much, much less likely to go to the ICU now during their stay. The clinicians have become more used to seeing what the impact of CAR T is on the patient. And they know a little better not to be so quick to pull the trigger and transfer the patient to the ICU. We will definitely have data on that as well, as we as we move forward. That's a key that's a key contributor to the cost of that stay over and above the cost of the drug itself.

And our anecdotal evidence suggests that ICU stays are going down as well. I do find it interesting that that our data in this study do support that, in that ICU stays for the CAR T patients, while slightly higher in prevalence during the inpatient stay, they stayed in the ICU for less for a shorter period of time than for both auto- and allo- stem cell transplant patients.

AJMC®: There's been a lot of discussion over the last 2 years about whether CAR T cell therapy should be administered earlier in the course of cancer treatment, when patients are still relatively healthy. The idea is that the treatment would work better, that it would avoid some poor outcomes; and avoid treatment patients with therapies that aren’t going to work. The idea is, “Maybe we would avoid the complete cost of one therapeutic regimen completely and go straight to CAR T.” Is there anything in these data, or other data that you’re working with, that would speak to this issue?

Kilgore: Yes, in this study, these were matched samples of patients. As you may recall, between CAR T auto and allo (HCT); in one of the we matched them on patient characteristics, and ECOG performance status and the presence of certain comorbidities, which impact the treatment decisions in this sample.

What we were unable to do was … to look backwards in time, as far as we could, so that we could match patients based on prior treatments to get a better sense of where these patients were. These are relapsed refractory DLBCL [diffuse large B-cell lymphoma] patients; it's an aggressive disease, and they're going to treat it aggressively. And so, can we match the patients on how much prior treatments that they have had? We couldn't do that in this study, because our sample was small. And as we look backwards in time, our sample got smaller and smaller …

What we did identify as we tried to match them and look back is that the stem cell transplants tended to have standard first line, CHOP plus rituximab, or related and then a single course of chemotherapy, which was preparatory for their transplant of a small number of patients had maybe 3 lines of treatment prior to stem cell. But in general, the pattern came out very clear. In contrast to the CAR T patients that we looked at, who tended to have prior to their CAR T, 2, 3, 4, 5 prior lines of chemotherapy.

We ultimately a sample got too small to take that into account. And so that is data that that is kind of behind the scenes data I wanted to share.

At the same time, we do have another study at ASH. While it's not a CAR T study, it looks at burden of illness of stem cell transplants in this same population-- the relapsed refractory DLBCL patient.²

We found that so these were patients who were in our Medicare fee-for-service data, so they’re elderly with relapsed refractory DLBCL. Seventy-five percent of the patients with relapsed refractory never even received a chemotherapy regimen using NCCN guidelines as intended to get a stem cell transplant, [but] these patients had a fair number of third, fourth and fifth lines of treatment after that.

In addition, when we looked at the patients in this population, who got a second-line treatment that was intended for stem cell transplant about 75% of those patients who got a second-line treatment intended [as preparation] for stem cell transplant, they never got a stem cell transplant, either. What they did get in about 30% to 40% of the cases was additional lines of treatment, …30% to 40% of them had third, fourth, fifth line of chemotherapy beyond that second line treatment. And that suggests a while not specifically to your question about [having treatment] earlier, that suggests that there is a large population out there who are deemed inappropriate for stem cell transplant and who never get it, or never get a preparatory regimen. Even those who do may not respond well or they have trouble tolerating therapy, and that presents an opportunity for CAR T to be considered a little sooner than to just continue to try additional lines of therapy.

AJMC®: It's a lot to consider. That’s the argument that some are making—you’ve spent all this money, you've put the patient through all of this treatment and it doesn’t work. But if you had tried CAR T right out of the gate, it might have worked better, and you would spend less in the first place.

Kilgore: That’s right. We can look at the cumulative cost. But there’s the opportunity costs, the humanistic outcomes as well. Chemotherapy is hard on a patient.

AJMC®: Is there anything that we haven't covered on this topic that you'd like to discuss?

Kilgore: One of the key takeaways from this study is that CAR T is new, and that stem cell transplants, whether they be autologous or allogenic, are well understood. The variation in costs are less. They have their own drugs, and that of course leads to a certain consistency and treatment.

In CAR T, the field is still gaining knowledge and a comfort level. What we need to remember is that despite those advantages to stem cell transplants, they are not free. They have costs before the procedure itself. In our study, we looked at 6 months pre vs 6 months post, examining health care utilization, and costs tended to be higher than CAR T prior to the procedure for both auto and allo transplants, Costs were higher during the 6 months post for allo HCT, and were materially higher than Carty. This leads to potential cost offsets, which tend to offset some of those costs associated with the CAR T and stem cell procedures themselves. If you just look at the procedure, you're only getting half the story. You need to look at what happens before and what happens after when you consider the full course of therapy.

References

1. Mohammadi I, Purdum AG, Wong AC, et al. Cost and health care utilization in relapsed/refractory diffuse large B-cell lymphoma: a real-world analysis of Medicare beneficiaries receiving chimeric antigen receptor T-cell vs. autologous and allogeneic hematopoietic cell transplants. Presented at: 62nd American Society of Hematology Annual Meeting and Exposition; Virtual, December 5-8, 2020. Abstract 2500.

2. Kilgore KM, Wong AC, Snider JT, et al. Burden of illness and outcomes in the second-line treatment of large B-cell lymphoma: a real-world comparison of Medicare beneficiaries with and without stem cell transplants. Presented at: 62nd American Society of Hematology Annual Meeting and Exposition; Virtual, December 5-8, 2020. Abstract 2548.