September 24, 2018
By Julie Gould
Podcast Series: In this episode, Elizabeth Budde, MD, PhD, assistant professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope, discusses recommendations that were recently created by a National Comprehensive Cancer Network task force for use of CAR-T therapy and also explains why she is concerned about current reimbursement models for CAR-T therapies.
First Report Managed Care: First, can you give us a little bit about your background and what the National Comprehensive Cancer Network is?
Dr. Budde: Sure. My name is Elizabeth Budde and I’m a hematologist at City of Hope. I’m also an immunotherapist with a focus on CAR-based therapy and antibody-based immunotherapy. My clinical research is focusing on patients, treating patients with lymphoma and leukemia and transplants and my clinical research interest is designing early stage research on CAR-T cell therapy.
NCCN is a National Comprehensive Cancer Network that comes up with guidelines, for treating cancers and the associated complications. The guidelines usually will be provided by a committee with experts from multiple comprehensive cancer centers who have expertise in treating a specific type of cancer or managing a specific type of toxicity. So, for example, immunotherapy-related toxicities, and the committee will meet regularly throughout the year, multiple times a year, and will update the guidelines in a very timely manner. So, it is the guidelines that are being translated into multiple languages as well worldwide. So, it’s not just a guideline for physicians in the United States, but it’s also being used as cancer care for cancer patients worldwide.
First Report Managed Care: I didn’t realize any of that, that it was worldwide, but that’s very interesting.
Dr. Budde: Yes, it is on multiple websites and can be seen in Chinese, Japanese, Spanish, multiple languages.
First Report Managed Care: Can you discuss what the NCCN Task Force was that was created to review the CAR-T therapies for your recent study?
Dr. Budde: Sure. So, the NCCN CAR-T Task Force was formed due to the demand in the field that CAR-T cell therapy was a therapy that offered the clinical trial last year. But at the end of last year, two of the approved products became available and more and more CAR-T-based clinical trials are ongoing right now. But there’s really an increasing need for NCCN to look into the matter and come up with recommendations really to guide the practice and guide the management of our CAR-T patients. So, therefore, this task force was formed in early this year, I want to say in March 2018.
First Report Managed Care: Can you go into detail about the issues that the task force observed during your report and how they were addressed?
Dr. Budde: So the task force had a very productive meeting. We discussed the mechanism of action, CAR-T cell design, the manufacturing, and the clinical treatment process. We also spent time discussing the efficacy and we observed the toxicities and how managing the toxicities differs in different places. In addition, the task force also focused on a very critical issue. That is the reimbursement and how to make it more available for patients.
First Report Managed Care: Do you feel that the benefits of CAR-T therapy outweigh the risks such as toxicity that is often associated with the treatment?
Dr. Budde: Yes. If you look at the pivotal or registration trials that led to the CAR-T approval, the efficacy of both the C19 based CAR-T therapy for acute lymphoblastic leukemia and diffuse large B-cell lymphoma, the efficacy, the result rate is a unprecedented before the response rate is in the 80%. For lymphoma, the results rate is over 60%. So, we never had any treatment for patients with similar disease conditions had such a high response rate. But definitely, the efficacy is there for those two approved products.
The toxicity is a significant issue too, but as we treat more CAR-T patients we learn more about the mechanism of CAR-T therapy and management of those patients, I foresee that the toxicities will become more and more manageable, and with more education, the toxicities can be managed and the benefits will definitely outweigh the risks.
First Report Managed Care: Do you feel that right now where we are with CAR-T therapy that the risks impact patient decisions to follow through with the treatment or, do most patients choose to follow through with CAR-T therapy?
Dr. Budde: So, for most patients nowadays, if they need CAR-T therapy, they’ve run out of options, so they don’t have more types of care for their disease. Also, most often, they’re desperate and yes, you’ll be required to have a discussion between the treating physician and the patient to go through the benefits of meeting the efficacy of the treatment. And also, to go through the potential risks and toxicities. So, I think that a good discussion would then lead to a good decision, whether the patient is indeed eligible for CAR-T treatment and whether they’re well informed of the risks.
First Report Managed Care: Do you see a day where CAR-T therapy will be able to treat solid tumors or other diseases outside of hematological malignancies?
Dr. Budde: Absolutely. If you do a search within PubMed you see more and more pre-clinical studies using CAR-T cells for solid tumors in the pre-clinical setting or in mouse models or in vitro studies. Even in the pre-clinical, in the early stage clinical trials, there are more and more different kinds of CAR-Ts and different treatment methods are being developed for patients with solid tumors. At the same time, we also begin to understand more about the so-called hostile micro environment in solid tumor settings. So, I’m pretty hopeful that soon we’ll see a breakthrough in treating solid tumors with CAR-T cell therapy.
First Report Managed Care: Can you discuss the challenges with making CAR-T specific treatment guidelines?
Dr. Budde: So, I think the most difficult challenge is not all CAR-T cells are the same because they can recognize the same antigen, but they can have different CAR-T signs by different manufacturers, and different end products. So, therefore, it’s very difficult to have a predictable side effect toxicity because they all differ and that can affect the toxicity profile. So, therefore, it’s hard to have a very strict guideline for all CAR-T cell therapies. The guideline needs to be flexible but also with safety in mind.
First Report Managed Care: Do you believe that standardized reimbursement structures will be adopted as possible payment policies, and why is that important? And if they are not adopted into policy, do you feel patients will not have complete access to all potential treatment options?
Dr. Budde: This is a very good question. I’m very concerned that with the way nowadays of reimbursement works, it will become very unsustainable to continue to offer CAR-T cell therapy for patients who otherwise would benefit from it.
First Report Managed Care: Do you think the more CAR-T therapies that are approved, the more expensive they’ll get or, do you see competition decreasing the cost of some of these therapies?
Dr. Budde: I think with more CAR-T cell therapies approved, the competition will definitely will build there and so I think more importantly, because the CAR-T cell therapy is still relatively new, we don’t have enough long-term outcome data to support the durability of the response, or even cure. If the CAR-T cell therapy can lead to a substantial portion of patients a very durable response or a cure, then the high cost of drugs compared to other types of salvage therapies for the same problem might not be that prohibitive. Because if you factor in all the years that the quality of life, the other years that the treatment can provide for the patients and the complications or other treatments, so the end cost might not be that much higher than the current treatment. But we don’t know that yet, so it’s important to have good, long-term outcomes analysis. There’s also a need for CMS for private payers to really seek a way to allow patients who otherwise are eligible for CAR-T treatment now have the chance to have the treatment.
First Report Managed Care: Finally, do you have any further comments to add about the NCCN recommendations and the overall future of CAR-T?
Dr. Budde: So, what I’d like to add is I think there are many, many, more and more people are learning about and many CAR-T now. I think that early referral is always a key because the CAR-T cell therapy is so specialized not all centers can offer CAR-T cell therapy. These patients’ benefit is they get CAR-T cell therapy at the right time. If you wait too long, it definitely takes time to coordinate. So, therefore, to have benefits, early referral to a CAR-T center is really key.
First Report Managed Care: I really hope that CAR-T is continually becoming more popular and I know it’s just in the news more and more often, so hopefully it will be adopted by more facilities for these patients.
Dr. Budde: I certainly hope so. I think that more facilities will be. We also have to be very careful about whether the treatment centers or facilities are able to manage the toxicity in the structure and a guided way. Because patient safety is also very important so, therefore, at least for now there are two FDA-approved products only available in certain centers but not in all of the treatment centers.
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