As cancer treatments continue to evolve, developments in immunotherapy and cellular therapy treatments could potentially drive a shift away from chemotherapy as the primary treatment for select cancers. Certainly for patients with lymphoma, it is possible to imagine a not-too-distant future wherein traditional chemotherapy no longer has a treatment role in this disease and, instead, is replaced by immunotherapies with chemotherapy serving as a conditioning regimen prior to chimeric antigen receptor (CAR) T-cell treatment. As such, it is imperative that pharmacists be involved at the forefront of this emerging development.
The exact role of CAR T-cell treatment will become clear with longer-term, follow-up data from studies that elucidate the best timing of CAR T-cell therapy within treatment. Staying informed of the ongoing CAR T-cell trials can be challenging given the increasing amount of new data. Nonetheless, pharmacists should stay abreast of the new studies, review articles, consensus guidelines, and FDA approvals of CAR T-cell therapies (see the TABLE). Additional products are expected to gain approval soon, with still more currently in development.
MD Anderson Cancer Center in Houston, Texas, is a 681-bed facility dedicated exclusively to providing cancer care, research, education, and prevention. Having participated in many of the CAR T-cell trials, we have been utilizing this therapy for a number of years, with pharmacists playing an essential role in managing patients undergoing treatment. CAR T-cell therapies have obtained FDA approval, increasing their ease of use. Because additional therapies and indications are expected to receive FDA approval in the near future, centers providing CAR T-cell therapy must continue to adapt to the varying requirements of each product.
Adapting the electronic medical record (EMR) to meet the needs of patients receiving CAR T-cell therapy is critical. This approach allows us to add system checks to aid in avoiding the use of contraindicated medications, such as corticosteroids or central nervous system active-medications that may interact or confound the assessment of toxicities in patients receiving CAR T-cell therapy. The supportive care medications and laboratory monitoring required for patients receiving CAR T-cells are also included in the order sets; this is particularly helpful in allowing us to ensure the labs are ordered correctly and on time. The order sets are also designed to support aggressive management of any toxicities with the as-needed supportive care medications, such as tocilizumab. With a thorough order set, we can ensure the appropriate medications are readily available should any complications arise.
Managing Acute Toxicity Risk
Accompanying these treatments is a significant risk of toxicity, which can be severe and even fatal. To manage toxicities, we developed a CAR T-Cell Therapy-Associated Toxicity (CARTOX) committee to oversee adverse event management and prevention.1 In order to address all possible complications, the committee operates from a multidisciplinary perspective. Members include hematologists, oncologists, pharmacists, and nurses, as well as representation from supportive care staff, including critical care, cardiology, and neurology, among other specialists.
Given the incidence and severity of the toxicities, the CARTOX Working Group was created in conjunction with investigators from multiple institutions and disciplines in order to create a treatment algorithm for monitoring, grading, and managing CAR T-cell related toxicities.1 This valuable algorithm reflects the expertise developed by investigators from a variety of institutions; thus, it delivers comprehensive guidance. Supportive care steps are outlined, including baseline imaging, cardiac monitoring, and seizure prophylaxis; recommendations are likewise included for monitoring, grading, and managing the acute toxicities associated with CAR T-cell therapy, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). A consensus on grading CRS and ICANS was recently published by the American Society for Blood and Marrow Transplantation.2
Studies have shown 13% to 46% of patients receiving CAR T-cell therapy will experience grade 3 or greater CRS.3-5 ICANS is less common, but carries significant risk for severe reactions and death.1 CRS is treated with tocilizumab, while dexamethasone is used for the treatment of ICANS; in both cases, a timely response to these conditions is imperative. As such, pharmacists should establish a method for sequestering tocilizumab. Two doses of tocilizumab are required to be sequestered for each patient, so in addition to operationalizing the process, budget must be established to accommodate maintaining these expensive products in inventory to meet the Risk Evaluation and Mitigation Strategies (REMS) program requirements.
The handling requirements for CAR T-cell therapy are complex. While the FDA approved the treatment as a drug, it must be handled like a cell therapy. Adherence to REMS program requirements is critical during the dispensing process. Additionally, a financial approval team should work with insurance companies to gain approval for this costly therapy. Timely approval is vital as oftentimes patients have few remaining treatment options.
From a staffing perspective, a clinical pharmacist should be a member of the team caring for patients undergoing CAR T-cell treatment to monitor for CRS and ICANS on a daily basis while also overseeing supportive care interventions for short-term issues, such as nausea, vomiting, and headaches, as well as longer-term issues, such as varicella-zoster virus prophylaxis, B-cell aplasia (which may require IVIG), and Pneumocystis jirovecii pneumonia prophylaxis; some patients require fungal or bacterial prophylaxis as well. Because the acuity of these patients is high, having a clinical pharmacist on the team is imperative to guide the supportive care efforts and oversee timely interventions as needed.
Change will be a constant in the near future as immunotherapies continue their rapid evolution; pharmacists’ training and education on these therapies will need to keep pace. Looking ahead, we can expect that the use of immunotherapy medications will expand as new products enter the market and existing medications receive additional indications. Similarly, as more data becomes available on effective supportive care and approaches to reduce treatment-related mortality, we can continue to optimize the supportive care interventions. All of this expansion will require additional involvement and oversight from the pharmacy department. Facilities will need to invest in educating and training pharmacists on the latest developments related to immunotherapy.
It should also be noted that the FDA requires REMS for the currently approved CAR T-cell therapies. Accordingly, pharmacists need to be trained and enrolled in the REMS program. Cell dispensing is a new approach for pharmacists and also requires additional training. While the pharmacy department is familiar with compounding cleanroom requirements, cell therapy cleanrooms introduce entirely new issues. With the possibility that future CAR T-cell therapy may require manipulation, this is an area that will require further professional development for pharmacists.
To stay abreast of this rapidly evolving field, pharmacists should remain up-to-date on the published studies as well as presentations at professional societies. It is important to note that information can rapidly become dated in this field as developments continue to occur. Pharmacy must be both flexible and collaborative as new challenges emerge in conjunction with these exciting new therapies.
- Neelapu S, et al. Nat Rev Clin Oncol. Published online 19 Sep 2017. doi:10.1038/nrclinonc.2017.148.
- Lee DW, et al. Biol Blood Marrow Transplant 2018 Dec 25. pii: S1083-8791(18)31691-31694. doi: 10.1016/j.bbmt.2018.12.758.
- Neelapu SS, et al. N Engl J Med. 2017;377:2531-2544.
- Schuster SJ, et al. N Engl J Med. 2019;380(1):45-56.
- Maude SL, et al. N Engl J Med. 2018;378:439-448.
Brandon Shank, PharmD, MPH, BCOP, is a clinical pharmacy specialist at the University of Texas MD Anderson Cancer Center.
The author acknowledges editorial support from Pharmacy Purchasing & Products editors in creating this article.
Part 1 of a 2-Part Series: Elements of a USP <800> Compliant Cleaning Program
Conduct a Drug Diversion Investigation
Special PP&P Buyer's Guide: Temperature Monitoring
Develop a Pneumococcal Vaccination Program
New & Noteworthy
- In The Loop!
- Digital Edition
- Special Announcements