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Clinical Pharmacy Manager, Blood and Marrow Transplant Program
Division of Hematological Malignancies and Cellular Therapeutics
PGY2 Oncology Residency Program Director
The University of Kansas Cancer Center
Zahra Mahmoudjafari, PharmD, BCOP, DPLA, has disclosed that she has received consulting fees from Bristol-Myers Squibb, Coherus, GlaxoSmithKline, Incyte, Medexus, Merck, Novartis, and Omeros.
As CAR T-cell therapies become available as treatment options for more patients with hematologic malignancies and potentially even solid tumors, pharmacists in both community and academic practice are increasingly likely to have a key role in caring for these patients. Below, I share my perspective on what pharmacists should know about these important therapies and provide recommendations specific to those in the community and in centers authorized to administer CAR T-cell therapy.
What All Pharmacists Should Know About CAR T-Cell Therapy
Pharmacists should be familiar with the operational logistics of administering CAR T-cell therapy, particularly those either joining an authorized center or working at a center that is inaugurating a CAR T-cell program. The process encompasses everything from patient referral and navigation to the logistics of bridging therapy, lymphodepletion, CAR T-cell infusion, and toxicity management. Some unique nuances include whether pharmacists or the cell therapy lab should verify and label CAR T-cell products that have been received at the center. Some centers routinely have the clinical pharmacists review, verify, and label the CAR T-cell product, while others do not incorporate this in the pharmacist workflow. Centers also vary on how adequate supply of tocilizumab is maintained for toxicity management, as discussed below.
Per the REMS programs for approved CAR T-cell products, all healthcare professionals who prescribe, dispense, or administer these products should be trained on the unique toxicities of CAR T-cell therapy—specifically cytokine-release syndrome (CRS) and immune effector cell–associated neurotoxicity (ICANS). The REMS programs also require 2 tocilizumab doses to be available within 2 hours of infusion for any patient undergoing CAR T-cell treatment. All pharmacists who care for CAR T-cell recipients should understand the use of tocilizumab for CRS, from its mechanism of action to the current literature on alternative agents to use when tocilizumab is ineffective. Pharmacists also need to be well versed in when and how to use steroids for CRS and ICANS.
Of note, there is currently a shortage of tocilizumab due to its use for COVID-19 management. At our center, we round the dose to the nearest vial size and have minimized tocilizumab use by capping the amount at 2 doses per patient even though our algorithm allows up to 4 doses. After the patient has received 2 doses, we switch to alternative agents.
Manufacturers have issued notices on updates to the REMS program stating that the first dose must be immediately available, but the second dose can be available within 8 hours of the first dose. The manufacturers have also noted that if healthcare professionals deviate from the REMS requirement by, for example, using just 1 dose of tocilizumab and switching to an alternative agent because a second dose is unavailable, then they document this for auditing purposes to the manufacturer and the FDA.
Patient and Caregiver Education
Pharmacists are integral to patient and caregiver education. At my center, we educate on bridging chemotherapy, lymphodepleting chemotherapy, and the CAR T-cell product itself. All pharmacists should be familiar with these therapies.
Recommendations for Pharmacists in Community Practice
For those in community practice, I would most emphasize the importance of understanding bridging and lymphodepleting therapy, being well-versed in patient and caregiver education, and understanding both the acute and long-term toxicities of CAR T-cell treatment and how to manage them. Long-term toxicities include hypogammaglobulinemia and cytopenias.
Recommendations for Pharmacists in Authorized Centers
Most authorized centers have established many standardized procedures with CAR T-cell therapy; therefore, it is essential for a pharmacist at an authorized center to understand these institutional recommendations. It is also critical to understand the process by which tocilizumab is secured and dispensed in the acute phase period.
To ensure consistency among team members, we have found standardized education sheets to be quite useful. These ensure that all healthcare professionals provide the same accurate information to patients and caregivers. We have also designed consistent order sets for admission and toxicity management. Our admission order set has our standardized prophylactic antibiotics and seizure prophylaxis as an example.
Toxicity management is round-the-clock and adverse events can happen anytime, so having management standardized is important. Pharmacists play a key role in developing standards and creating order sets. We have incorporated ICE (immune effector cell encephalopathy) monitoring for ICANS assessments performed by our nurses and entered into electronic medical records (EMR). This allows for the multidisciplinary team (including our pharmacists) to monitor for any trends suggesting neurotoxicity. We have also implemented best practice advisories (BPAs) in our EMR to notify the care team of a CAR T-cell recipient. The BPA cautions against steroid administration unless these are to be used for the management of CRS or ICANS. Patients also have a temporary contraindication for steroids in the allergy section of their EMR. Additionally, we have BPA for the emergency department to notify of patient CAR T-cell status and to avoid steroids and notify a CAR T-cell physician.
CAR T-cell therapies are fast becoming an established treatment modality for hematologic malignancies. Pharmacists in both community and academic practice settings can play a significant role in optimal patient outcomes with these treatments.
What challenges have you faced when caring for a patient who will be receiving or has received CAR T-cell therapy? Answer the polling question and join the conversation by posting a comment in the discussion section.
To get individualized recommendations on CRS and ICANS management from multidisciplinary experts, please visit CCO’s Interactive Decision Support Tool: Assessment and Management of CAR T-Cell Toxicities.