CAR T-Cell Therapy for the Management of Multiple Myeloma - Episode 8
Hematology/oncology experts explain why early referral to an academic center is important when approaching a case of relapsed/refractory multiple myeloma, especially as CAR T-cell therapy becomes a viable option for certain patients.
David S. Siegel, MD, PhD: The history of oncology is that we figure things out empirically. For example, “Here’s a new shiny toy. Let’s just try it. Some will like it, and some will not.” As such, we’re not that far from that now. The ability to identify who is an appropriate patient is one of the holy grails of oncology in general. Therefore, as we get into these new technologies that are extraordinarily expensive, these new technologies some of which have significant toxicities, we need to be able to predict who is going to respond and who is not.
The studies with CAR [chimeric antigen receptor] T cells that are going on now do show populations that are more likely to respond and less likely to respond, so we’re going to have to apply that information. Notably, that hasn’t really been the tradition of oncology. Instead, the process has been, let’s try it in as many situations as we can and then pick the best one.
My hope would be that we have the biomarkers and the ability to assess both the disease and the patient to know who to apply these extraordinarily complex, expensive, and potentially toxic therapies to, before we bring the patient in and start.
Parameswaran Hari, MD, MRCP: Early evaluation by an academic center where CAR T cells can be delivered will become a central piece of the strategy for patients with multiple myeloma [MM] going forward. It would be a shame if a patient who could’ve gotten CAR T therapy 6 months prior, for example, ends up waiting, or not getting referred, or not being able to be seen in a timely fashion at an academic center, which results in a negative outcome for the patient. I would emphasize that early referral will remain a key plank on which the CAR T success in the real world will need to be built on.
The logistics of CAR T dictate that the therapy will only be available in a limited number of centers in each state. Typically, these are going to be the large practices, or practices that have ability to do CAR T currently for lymphoma, for example, or those that are already doing stem cell transplantation for MM. In these kinds of centers across America, the availability varies quite widely, which will become an access issue as most patients, almost 80% of patients with MM, are treated in the community and treated near their homes where they live. These patients will have to be educated early on that if things don’t go as planned and relapses occur, then they will need to go to a CAR T-cell center near them and begin a CAR T program. Again, there will be multiple visits that the patients will have to understand, and their referring doctors will have to understand. Specifically, they will have to understand that the use of certain agents, especially high-intensity alkylator drugs, medications such as bendamustine, might lead to depression of their T cells. As a result, CAR T cells may not be able to be manufactured from patients right after these agents have been given. As such, what they are on right before referral also is an important consideration.
Once the patient is referred, they will need to come for CAR T-cell collection at a center, and will then have to do bridging chemotherapy, often close to their own doctors and close to home. From there, they will have to come down once the CAR T cells have been made. The median time for making these CAR T cells and getting them back from the manufacturing site is about 4 to 5 weeks. In that period, the patient has hopefully remained stable and on therapy, so that when the CAR T cells are eventually made, the patient can come down to the CAR T-cell center, get admitted, or stay near the center for 2 to 4 weeks, during which time they receive the CAR T cells and are monitored for [adverse] effects. Once they recover completely, they can go back. All of this is a logistical challenge for the patient. It’s a referral challenge for the referring physician, and an acceptance challenge and logistical challenge at the CAR T center, too. It will need close coordination between all 3 parties.
I always encourage earlier referral for patients to the CAR T-cell centers. Earlier referral achieves multiple objectives. One is that most of these therapies are going to paid for by Medicare or other third-party payers. Specifically, third-party payers sometimes need preapprovals, while Medicare does not. The patients requiring preapproval will need quite a bit of time for the approval process to happen, and time is life in this situation. Therefore, the earlier the referral happens, the more options the patient has to keep the disease at bay, even if the approval process is long. Second is the slotting for patients for pheresis. CAR T cells need to be gathered in the form of T cells from the patient, and then manufactured at a remote site. The gathering of T cells, which is a process of cell collection, or pheresis, will need a slot allotted for the patient, and these slots are difficult to come by as the pheresis machines are typically always busy in the CAR T centers. To get on those kinds of lists to get T cells collected quickly requires a lot of coordination, and early referral is needed. If a late referral happens, the MM typically is out of control at that point, and patients may not be able to wait to get on these collection schedules, insurance approvals, etc.