Matthew Lunning, DO: Typically a patient is seen by a lymphoma physician. In our institution the CAR T-cell physician and the lymphoma physician are the same person. What may change is that if we are thinking that this could potentially be a patient receiving CAR T-cell therapy—whether or not it’s a clinical trial or commercial patient—each one of those individuals is alerted that we have a potential CAR T-cell patient.
We have a nurse research manager for our CAR T-cell patients that are going towards a clinical trial. We have a nurse case manager that navigates the commercial space for both our availability for axicabtagene ciloleucel [axi-cel] and tisagenlecleucel [tisa-cel]. Once that patient has been seen—they often meet both myself or one of my colleagues as well as the case managers for both settings—it’s kind of a parallel race. We’re looking to see if they are eligible for clinical trials: Does their pathology state and diagnosis show that we could get approval for CAR T-cell therapy on a commercial standpoint, or in the clinical trial standpoint?
We’re then doing the same eligibility checks in the commercial setting that are often done in the clinical trial setting. Do they have adequate pulmonary function and cardiac function? What is their renal function when we’re looking down the road for menthol-depleting chemotherapy?
What is their prior treatment history in consideration of possible tisa-cel treatment, bendamustine [Bendeka], instead of Cytoxan fludarabine? What are their counts? Maybe we don’t give lympho-depleting chemotherapy. We’re having these discussions several times a week. I try to meet with our CAR T-cell team at least every other week to assess the list of patients and where they’re at: what’s their insurance approval? That is one of the big things we’re going to consider. The financial person is the next person we’re calling if we’re thinking the commercial route.
We also ask: Who have we worked with before from an insurance standpoint versus somebody from a new financial background? We’re really in the single-payer contract arena right now; we’ll move past that eventually. We sort out the Medicare issue because we have to. They’re our patients—and for the citizens of the United States, we have to figure out the Medicare situation for their potential benefit.
There are many different streams of processing going on. They’re meeting with social workers because there is a commitment to time if they’re traveling from outside the region of my institution. We have to work on housing for when they’re receiving CAR T-cell treatment, and where their caregivers are going to stay during the process. We tell them this can be a tag-team event. It doesn’t have to be 1 person who’s the caregiver.
Then we have time after the apheresis to talk about how to keep the patient’s disease under control so that when the CAR T cells come back, we’re ready to begin lymphodepletion and infusion.
In the post-fusion setting, our patients become inpatients. There’s an experience with tisa-cel of giving the construct to outpatients. With improved understanding of the safety profile in the commercial setting, maybe we will venture into the outpatient arena for administering lymphodepletion and infusions. Seeing those patients daily to assess for the onset of cytokine release syndrome [CRS] or neurotoxicity would then require their admission.
Currently, our patients for axi-cel are being given lymphodepleting chemotherapy as outpatients and thereafter admitted for CAR T-cell infusion. They typically are spending anywhere from 10 to 14 days without CRS or neurotoxicity in the hospital. If there are CRS or neurotoxicity events, they may be in the hospital for longer.
Once they’re discharged and in the outpatient setting, they’re seen once or twice weekly depending on how their CAR T infusion went, what their counts are, and if they require transfusions. It’s an individual process.
Leo Gordon, MD: The workflow for CAR T therapy is perhaps similar to what it is for stem-cell transplantation. At our institution, because almost all the patients we’ve treated so far have been on clinical trials, we’re doing this with our clinical research office. We have a coordinator, a nurse coordinator, and several data managers assigned to this program as we increase the number of diseases in which we’re looking at CARs. And to include chronic lymphocytic leukemia and myeloma, I think we’re going to need more clinical research folks doing the work with us. As we evolve to commercial use of the drugs, we will evolve a coordinator position for all CAR T efforts.
Our intent now is to have a coordinator for the whole program. Once patients are sent to clinical trials, they’ll go to a clinical trial person. If they’re going to commercial, they’ll be managed mostly by our lymphoma program—we have nurse practitioners associated with each faculty member. The nurse practitioners involved in the treatment of lymphoma are going to be the ones that are going to be working on the commercial CAR-T product. We have a separate unit for those patients on clinical trials. Our developmental therapeutics unit is for early phase clinical trials; we have nurse practitioners and nurses and ancillary personnel that are helping us manage those patients.
Every institution has to figure out what works best. Having an intake person and the coordinator—at least 1 or 2 as the volume grows for this—is going to be extremely important.
There haven’t been any CAR T trials other than in the United States. China has myeloma trials, which is an exception. We are getting calls from around the world from patients, so we have involved our international office in that process; they’ve been very helpful in trying to get through some of the problems we have. These patients are obviously coming without any insurance, and there is a huge co-pay to figure out. Each institution has to work that out for themselves. This is going to change somewhat because there are studies just opening in Europe. Novartis is opening a trial in Europe.
Transcript Edited for Clarity