Chicago, IL—Chimeric androgen receptor (CAR) T-cell is a form of gene therapy now used in some relapsed and refractory malignancies. Although this type of treatment 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 there is no denying its high cost, often upward of $1 million per course of treatment.
According to Julie Kennerly-Shah, PharmD, MS, MHA, BCPS, Assistant Director, Pharmacy, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital, Columbus, pharmacists play a crucial role in successfully implementing CAR T-cell programs. There is a push from payers to treat CAR T-cell similarly to bone marrow transplantation for reimbursement, so pharmacy directors should be well-versed in various payment models. In addition, institutions should be cognizant that they may need to make operational changes based on new drugs entering the market.
Last year, the FDA approved 2 CAR T-cell therapies, axicabtagene ciloleucel (Yescarta; Gilead) for certain types of relapsed or refractory large B-cell lymphoma, at a cost of $373,000 per course; and tisagenlecleucel (Kymriah; Novartis) for patients aged ≤25 years with 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 has received so much attention is because it is not spread out over the course of multiple infusions. It requires a 1-time payment, which is difficult for patients and 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 Hematology/Oncology Pharmacy Association (HOPA) 2018 Practice Management Conference. “The landscape of oncology has transformed, and CAR T-cell is now another tool in our arsenal to treat patients.”
Key Roles in CAR T-Cell Administration
“I think one of the most important things you can consider when implementing CAR T-cell therapy is the various roles and responsibilities that are required. A multidisciplinary approach is required to make sure you are 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 responsible for 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 interfacing with the manufacturer’s 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 and intensive care unit (ICU) should be educated on all current guidelines around the management of cytokine release syndrome (CRS)—an oncologic emergency—including the administration of tocilizumab (Actemra; Genentech), if 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 [emergency department] and ICU are well-versed on CAR T-cell,” Dr Kennerly-
Shah noted. “CRS is one of the worst parts of CAR T-cell 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 and Operational Workflow
Pharmacy personnel should ensure appropriate dosing and timing of all medications in relation to each other and to leukapheresis (the collection of white blood cells from peripheral blood). 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 it when warranted, and build the electronic medical record.
The electronic medical record build should include any lympho-depleting chemotherapies and CAR T-cell therapies, including any prophylactic medications (ie, fluconazole, levofloxacin, acyclovir), premedications (ie, acetaminophen, diphenhydramine), laboratory monitoring (ie, ferritin, fibrinogen), and any 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. It’s not just one discipline that’s in charge of making this happen for patients,” she added.
She noted, however, 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 fact that these roles and responsibilities may change.
Dr Kennerly-Shah asserts that any individual that 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 training with other clinical, policy, and operational education required for staff, to maximize efficiency.
She recommends establishing clear roles and setting up a designated CAR T-cell staff, including a business manager, data manager, clinical staff, and financial staff, to serve as subject matter experts.
“There is really zero margin for error, so prep in advance,” Dr Kennerly-Shah said. “Have a designated person at the manufacturer who is assigned to your institution and can be contacted by anyone at any time.”
Additional Financial Considerations
There is no getting around the heavy financial burden of these treatments. Although one Institute for Clinical and Economic Review study found 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.
Numerous factors contribute to the cost of CAR T-cell therapy, 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. According to Dr Kennerly-Shah, inpatient treatment is not sufficiently reimbursed, 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. She said it is important to educate payers on the complexities of these treatments, and to establish a sense of urgency so that patients do not run out of time before their insurance company responds to their request.
“It is a [public relations] nightmare to think about the position we have 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 is 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-cell therapy differently because of the [public relations] 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), she added. In addition, consider patient responsibility, as many may have already met their out-of-pocket limits, and develop a charge structure for patients who are interested in paying cash for the therapy.
According to Dr Kennerly-Shah, financial considerations will continue to evolve as additional CAR T-cell products are brought to market and as payers refine their reimbursement models.
“There is fear on both sides. But we are all trying to figure this out together,” she concluded.