Chicago, IL—So far, 2 chimeric antigen receptor (CAR) T-cell therapies have been approved by the FDA for some types of relapsed or refractory lymphoma and leukemia. Although CAR T-cell therapy has shown promise in many patients who have run out of standard treatment options, it is incredibly resource-intense: the complexities of its administration require an interdisciplinary approach for success, the side effects can be severe, and its high cost can reach upward of $1 million per course of treatment.
There is a push from payers to treat CAR T-cell therapy similar to bone marrow transplant in terms of reimbursement, so pharmacy directors should be well-versed in various payment models.
According to Julie Kennerly-Shah, PharmD, MHA, Assistant Director, Department of Pharmacy, Ohio State University Wexner Medical Center–James Cancer Hospital, Columbus. In addition, cancer institutions should be cognizant of the fact that they may need to make operational changes based on new drugs that are entering the market.
Last year, the FDA approved the first 2 CAR T-cell therapies—axicabtagene ciloleucel (Yescarta) for relapsed or refractory large B-cell lymphoma, at a cost of $373,000 per course; and tisagenlecleucel (Kymriah) for relapsed or refractory B-cell precursor acute lymphoblastic leukemia, with a price tag of $475,000 per course.
One of the reasons the high price of CAR T-cell therapy has received so much attention is because it is not spread out over multiple infusions; CAR T-cell therapy requires a one-time administration and therefore a one-time payment, which is difficult for patients and for payers to absorb.
“I will not negate the fact that it is expensive, but expensive agents are not new to oncology care,” Dr Kennerly-Shah said at the 2018 Hematology/Oncology Pharmacy Association Practice Management conference. “The landscape of oncology has transformed, and CAR-T is now another tool in our arsenal to treat patients.”
“A multidisciplinary approach is required to make sure you’re using it in appropriate patients, getting paid for the therapy, and managing adverse events appropriately,” said Dr Kennerly-Shah.
She recommends identifying individuals within the multidisciplinary team to serve as leaders in a number of key roles: the finance team should be in charge of negotiating single-case agreements with payers, ensuring precertification of every patient, monitoring reimbursement, and measuring the overall cost of care.
Members involved in leadership should be involved with guideline development and implementation, and should ensure proper and individualized education of staff related to CAR T-cell therapy and management of its associated adverse effects.
Cell therapy program coordinators should be held responsible for interface with the manufacturer portal, including entering patient data into the portal, scheduling encounters, and tracking patient progress with CAR T-cell therapy. Data managers should take on data collection and quality tracking, routine distribution of quality tracking reports to all stakeholders, and reporting on adverse events.
Nursing should facilitate patient-friendly communication around all aspects of CAR T-cell therapy, while maintaining a high level of training in recognizing and managing adverse effects.
The emergency department (ED) and intensive care unit (ICU) staff should be educated on all current guidelines related to the management of cytokine release syndrome (CRS)—an oncologic emergency—including the administration of tocilizumab (Actemra), when warranted. In addition to pharmacists, they must also ensure no steroids are administered to patients receiving CAR T-cell therapy.
“I cannot emphasize enough the importance of making sure the ED and ICU are well-versed on CAR-T,” she emphasized. “CRS is one of the worst parts of CAR-T therapy, and one of the most challenging things to manage; the key is to have advance consensus within the clinical staff as to how these adverse events will be managed, ie, not jumping to the use of rescue therapies prematurely.”
Pharmacy should ensure appropriate dosing and timing of all medications in relation to each other and to leukapheresis. They should also be able to recognize and manage adverse effects. A member of the team should be put in charge of reporting these events to the FDA, as is currently required; maintain stock of tocilizumab in the pharmacy; and administer as needed; and build the electronic medical record (EMR).
The EMR build should include any lymphodepleting chemotherapies and CAR T-cell therapies, such as any prophylactic medications (eg, fluconazole, levofloxacin, acyclovir), premedications (ie, acetaminophen, diphenhydramine), laboratory monitoring (ie, ferritin, fibrinogen), and the use of tocilizumab, in addition to all nursing communications.
“There’s an operational workflow and a stepwise approach to how we manage patients from start to finish,” Dr Kennerly-Shah said. “It’s not just one discipline that’s in charge of making this happen for patients.”
She noted that more than 40 CAR T-cell therapies are currently in various stages of clinical trials, so institutions should remain adaptable and amenable to the reality that these roles and responsibilities may change.
Dr Kennerly-Shah suggested that any individual who is in any way involved with CAR T-cell therapy should undergo training. She recommends a computer-based learning system using institutional software, as opposed to live trainings. She also suggests combining the required Risk Evaluation and Mitigation Strategy program training with other clinical, policy, and operational education required for staff, to maximize efficiency.
Establishing clear roles and setting up a designated CAR T-cell staff—including a business manager, data manager, clinical staff, and financial staff—can serve as subject matter experts.
“There’s really zero margin for error, so prep in advance,” she advised. “Have a designated person at the manufacturer who is assigned to your institution and can be contacted by anyone at any time.”
There is no getting around the heavy financial burden of these treatments. Although one study from the Institute for Clinical and Economic Review showed that CAR T-cell therapies do provide a net health benefit and are cost-effective in the long-term, the added healthcare costs may be difficult for the system to absorb over the short-term.
Many factors contribute to the cost of CAR T-cell therapy in addition to the difficulty in producing the therapy itself, including bridging chemotherapy, hospitalization, treatment of adverse effects (including CRS, neurotoxicity, and prolonged B-cell aplasia), and potential stays in the ICU. These factors make it difficult to prospectively predict how much will be spent on each patient.
There are also huge financial considerations related to inpatient versus outpatient treatment with CAR T-cell therapy. Inpatient treatment is not sufficiently reimbursed, according to Dr Kennerly-Shah, although the majority of patients who receive CAR T-cell therapy are treated in this setting.
Additional considerations include the operational costs of implementation, including the training of large numbers of staff, and the ongoing provision of care. It is important to educate payers on the complexities of these treatments, and to establish a sense of urgency so that patients don’t run out of time before their insurance company responds to their request.
“It’s a PR nightmare to think about the position we’ve been put in, and how much we have to mark up these drugs in order to get anywhere close to being paid appropriately for them,” she said. “I think it’s really the responsibility of pharmacy directors to be well-versed [on these drugs], to interact with chief financial officers, and to advocate that perhaps we should look at CAR-T therapy differently, because of the PR associated with it.”
Try to negotiate longer payment agreements, and consider cash flow (which can deplete quickly if expensive treatments are not reimbursed in a timely manner). In addition, consider patient responsibility, because many might have already met their out-of-pocket limits, and develop a charge structure for patients who are interested in paying cash for the therapy.
Financial considerations will continue to evolve as additional CAR T-cell therapies are brought to market, and as payers refine their reimbursement models.
“There’s fear on both sides,” Dr Kennerly-Shah said. “But we’re all trying to figure this out together.”
