Implications of Expanding Use of CAR T-Cell Therapy in Relapsed/Refractory Non-Hodgkin Lymphoma (NHL) - Episode 6
Jeff Sharman, MD, provides insight on patient eligibility for CAR T therapy, managing barriers to access, and steps for monitoring patients with R/R NHL post-treatment.
Jeff Sharman, MD: The patients who are most appropriate for CAR [chimeric antigen receptor] T are those individuals who have been diagnosed with large-cell lymphoma who have received standard frontline therapy with R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] or an equivalent regimen, experience disease relapse, have gone to stem cell transplant, and have then experienced relapse after transplant. Or those individuals who couldn’t get to transplant because their disease was not sufficiently sensitive to the salvage chemotherapy. These are going to be second- or third-line patients who are refractory. The details about the labeling information are going to be important and influence exactly who’s eligible for this therapy. Nonetheless, these are not your standard frontline patients by any means.
One of the big concerns about this disease having a high tempo is that oftentimes you have to move quickly for these patients in order to get them to whatever their next therapy is. If you can’t move quickly, sometimes time itself is what determines whether a patient is going to have a life-or-death outcome. Where that becomes particularly problematic is with access. A lot of these therapies may require patients to physically relocate within proximity of the treatment center. In a lot of communities, particularly a lot of Western states—I’m in Oregon—these are large moves. In our state, the only area where you can get CAR T therapy is Portland, and that can be a 5- to 6-hour drive for somebody living in Medford or Grants Pass. To physically relocate and move to an area for a month is a barrier for many of these patients to get access.
The hope is that what we can do is take very sophisticated medical practices. This is not going to be for every medical oncology practice, by any means, but for those practices who have existing transplant programs, perhaps very robust phase 1 capabilities, or a bandwidth to take on the ambitious project like this and allow this therapy to be delivered to patients in these practice settings. Therefore, enabling patients to get access to therapy that they might not otherwise get. I can tell you from my own experience, I have taken care of several patients already who presented with a life-and-death choice, a choice for life that required relocating, stated that that was an impossibility for them, that they couldn’t do it. It’s hard to overstate how important access andgeography are for patients to get this therapy.
When a patient is treated with CAR T, a lot of the reason for the more narrow distribution of the therapy is that the follow-up is intensive and recognizing some of the unique adverse effects of this therapy, the timing, and having the medical infrastructure in place to address these issues. We worry about neurotoxicity, which in many cases, is going to be subtle or mild or just present with some word-finding abnormalities but at its more severe stage can evolve all the way into seizures, obtundation, brain stem herniation—very dangerous outcomes. They’re not common, but you must presume that any patient being treated could experience these issues. Being trained on these, knowing how to recognize them, knowing how to bring on appropriate consultative services, having the hospital infrastructure in place, having protocols in place with the emergency department, the ICU [intensive care unit], the rapid-response teams in the hospital, and so forth.
The other toxicity that’s relatively common or needs to be familiar to the site is what we call cytokine release syndrome. For somebody who may not know what that is, it can look like a bad bacterial infection. It can look like sepsis, where patients have fever, low blood pressure, capillary leak syndrome, where they get fluid into their lungs, and have blood pressure that requires vasoactive medications—what we call pressors, to raise blood pressure. These are therapies that in most communities can be administered only in an intensive care unit setting. It’s 1 thing to be able to administer the therapy, but realistically the treating center has to be familiar and comfortable with addressing these unique adverse effects—cytokine release syndrome, neurotoxicity—that occur within the first month after therapy.
One of the unique aspects of CAR T therapy is that the existing products that are available oftentimes have a very rapid onset to their adverse-effect profile. You can see some of this cytokine release syndrome or neurotoxicity happen within 24 to 48 hours after administration of the product. As such, for products such as the Novartis [International] product or the Gilead [Sciences]/Kite [Pharma] product, these are administered within the hospital.
One of the unique aspects of the product being put forth by Juno is the possibility that these patients have fewer and more delayed adverse effects. It allows these patients to be treated in the outpatient setting, which creates several important socioeconomic considerations. Oftentimes it’s vastly less expensive for patients to receive therapy in the outpatient setting rather than in the hospital setting. There are the logistics of a hospital formulary product, and this is something that can be delivered outside a hospital formulary. That’s going to have the ability to expand access if this can be safely administered in the outpatient setting. That’s the protocol my center is currently working on.