In an interview with Targeted Oncology™, Bruce Feinberg, DO, discussed the use of CAR T-cell therapy in the community oncology setting, the challenges oncologist face, and the next wave of innovation to improve CAR T-cell administration for patients.
Thirty-nine percent of oncologists working in the community setting refer 2 out of 5 patients to receive chimeric antigen receptor (CAR) T-cell therapy at hospitals, according to data from a surveydisseminated by Cardinal Health Specialty Solutions.1
The research also showed that a decent portion of oncologists (27%), do not refer or administer CAR T-cell therapy at all, and a small proportion, 6%, perform in-office infusions. The survey raises questions about how to improve CAR T-cell availability for patients treated at community clinics. The recommendation born from the survey was to align stakeholders to address the concerns of the oncology population
In an interview with Targeted Oncology™, Bruce Feinberg, DO, vice president, chief medical officer Cardinal Health Specialty Solutions, discussed the use of CAR T-cell therapy in the community oncology setting, the challenges oncologist face, and the next wave of innovation to improve CAR T-cell administration for patients.
TARGETED ONCOLOGY: Can you discuss CAR T-cell therapies that are FDA-approved in hematologic malignancies? How have these therapies impacted treatment?
Feinberg: The story of CAR T goes back a little before the drugs were approved. The recognition that our view of cancer in general was thinking of cancer as an invader. The way we thought about bacteria or viruses so that they were the enemy that we are going to then destroy.The recognition that changed all that was rather than thinking about cancer as the external alien enemy, because cancer was created by cells, and they are human cells that are transforming, should we be thinking about how to then look at the problem a little bit differently and see it as a failure of the host, as opposed to the invader.The story really begins as we think about empowering the immune system. The first aspects of that go back to the 1980s with interferons, interleukins, and tumor-infiltrating lymphocytes, and that was the first round.
The second way begins as we started to now think about the mid-2000 teams with the immune checkpoint inhibitors and start to look at manipulating T cells. The T-cell manipulation that begins with CART is not stopping with CAR T. It is going to be developing into bispecific antibodies, and natural killer cells that are then manipulated, so we are going to be seeing a rapid expansion of this host empowerment, how we really trigger the immune system to do its job, and then control this process, which really is a process of self as opposed to the external enemy.
Now that we have CAR T cells, what are the key challenges community oncologists facewith giving this treatment to patients?
The good news regarding these challenges is that we have had these challenges before. I mentioned that we think back in the early first phase of empowering the immune system with treatments like interleukin-2, we have the same kind of problem intensive treatment performed in hospital patients in ICU environments. We have also had that same world-specific to hematologic malignancies when we think about transplant, initially allogeneic transplant and then with autologous transplant, but similarly intensive complex programs, and multi-step approaches to patient care often done in tertiary care academic environments. There has been a background that really helps this field move forward quickly, based on that prior experience.
But the barriers that we have witnessed are those barriers we have seen before. Having an educated community workforce of healthcare providers who are knowledgeable about these treatments, an academic, tertiary care environment, where they remove all the barriers to those patient referrals, and hopefully patients who understand to some degree that complexity of the program will be willing to undergo consent for those procedures. Each of those barriers exist, but each of those barriers has been seen before, and we can rely on past experiences to help guide us forward.
Cardinal Health conducted a survey around in-office infusion and referrals for CAR T-cell therapy. How did community oncologists respond?
The research has been focused on both understanding physician perceptions. Are these therapies ready for primetime? Do they adopt and support these therapies? If they do support and adopt, what are the barriers to being able to refer patients for these treatments? Then lastly, what are the outcomes of these patients by getting into the chart itself and understanding the outcomes of patients? We have done all that in recent years, and some of that work was just recently presented at iSPOR.
At iSPOR, particularly regarding diffuse large B-cell lymphoma, there were 2 observational research studies that were done. One looked at the feasibility of being able to use that electronic health record in the community oncologist office to be able to understand the full journey of the patient who undergoes CAR T therapy, and can it understand the scope and quality of the data that is housed within that medical record?
The second aspect of it was understanding. Could you be able to assess outcomes from the data within that medical record? So,2 parallel studies that were done specifically in diffuse large B-cell lymphoma, and also studies that have been done trying to look at new areas like multiple myeloma and understanding what physicians' perceptions about another hematologic malignancy in which there will be CAR T therapy available.
How do you interpret the findings from this survey?
For the community oncologist's electronic health record as a data source for conducting research on patients who are undergoing CAR T and other therapies, what we found is that the data source was rich and robust. For almost every major benchmark, in terms of the patient journey for CAR T,prior therapy, the timing of that prior therapy, the nature of that prior therapy, the referral to the tertiary center for consideration for CAR T, the actual evaluation for CAR T, the pheresis procedure, the site of the lympho-depletion procedure, chemotherapy, the actual administration of CAR T, the subsequent adverse event tracking, and the ER visits and hospitalizations, as well as the return to the community oncology clinic, all of that data was available within the community oncologist health record. That is a treasure trove of data that we can use as we start to expand the CAR T arsenal to understand the patient experience with CAR T in the real-world setting.
As we know, patients and clinical trials are often not representative of what is happening in real-world patients and clinical trials. First, less than 3% of adults with cancer participate in oncologic clinical trials, and those that do are healthier, they are less diverse, they are younger, they often are more health literate, and they have a higher socioeconomic status. That lack of representation becomes a problem that we start to extrapolate to all comers. Understanding what is happening in the real world to these patients is critical, and our data demonstrates that using the community oncologists to abstract the records is giving us that data that is necessary to understand the patient's experience. That is1 key outcome is that in the feasibility study, we saw as a strong positive for a new data source that can evaluate the real-world experience of patients undergoing CAR T-cell therapy.
The second outcome is that based on the feasibility of that data, could we find interesting details and insights about those patients being treated?We saw some interesting patterns of care that seemed to be geographically different. The timing of referrals and the nature of the CAR T-cell treatmentwere different as we looked across the major geographic regions of the country. Trying to understand that is going to be critical as the research continues, so are these trends and patterns related to Centers of Excellence and the KOLs, who often speak from those centers of excellence within a region?
Memorial Sloan Kettering often influences what happens in the Mid Atlantic, MD Anderson influences what happens in the South and the Southwest, and a center like UCLA influenceswhat's happens on the West Coast. As the Centers of Excellence have an influence, are we going to see differences in patterns of care in these different regions? Then, what were the outcome differences between those patterns of care?
Can you provide background on your study of CAR T-cell utilization patterns for relapsed/refractory diffuse large B-cell lymphoma in the US-based community hematologists/oncologists?
It has been almost 7 years since we first started to evaluate and publish on the broader world of empowering the host through immunologic therapies in the treatment of cancer. Our CAR T work now is 5 years, there have been a half dozen publications, similar tothe ones that we are talking about now, over the course of the past 5 years. We are trending that rate of adoption, that perceptions of physicians, the perceived barriers they find, and we are not just doing that assessment of physicians in the community, but we are also gathering experts from the major tertiary care centers to understand what they are perceiving as barriers and a general sense that CAR T therapy currently is under-utilized for those reasons and those barriers. What we find is there are still problems. The patients undergoing CAR T therapy have advanced disease, and are not clinically stable. The current timeline for CAR T, which can take 6 weeks from point of referral to point of CAR T-cell administration, often is problematic because of that patient instability.
Then, there are a host of new therapies which entered the armamentarium of treating physicians, which are making it confusing as to which is the appropriate second-line, third-line treatment. Recent data from ZUMA-7 [NCT03391466] trial has demonstrated that CAR T is a more effective therapythan autologous stem cell transplant as the first salvage treatment. That also adds a dynamic so that when we are doing this research, it can't be viewed as static. We have to be viewing it as a need for recurrent evaluations, as therapy indications change, and as new therapies come alive. Part of the basis for this research is really to be able to constantly trend what's happening in the field of newer therapies and how physicians perceive those new therapies and what are the outcomes of the patients. They're referring for those therapies. That was the focus of the work we've recently have done in diffuse large B-cell lymphoma.
Based on these 2 studies, how do you think the challenges that oncologists are experiencing with CAR T cells are impacting patient care?
I think overall, it is a good story. I think all physicians who treat cancer, particularly patients who have refractory or relapsed disease, for whom cure has been elusive, are looking for new therapeutic options. CAR T came with a tremendous amount of enthusiasm and excitement, but also with some concern about its toxicity. Now, we are seeing second- and third-generation CAR T therapies, we're seeing expanded indications for earlier line of treatment. I think that excitement continues, and I think reservations are decreasing.
I think communication between tertiary care centers and community oncologists is improving, and we're getting closer to that point where patients will not have to leave home and leave their communities for this treatment, but we are not there yet. We are still testing and trying to understand what it will take for community physicians to participate in this aspect of care. I think that is going to be the next wave of innovation, and it will be operational innovation, rather than just drug development innovation, on how we can get these therapies to be done closer to the time of need.