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Clinical Practice Spotlight: Preparing for Blinatumomab and CAR T-cell Therapies

  • Advances in Hematologic Malignancies Issue 4 Summer 2016
  • Advances in Hematologic Malignancies Issue 4, Summer 2016

    — Marsha Clements, RN, MSN/ED, Nursing Director, Brigham and Women's Hospital, Floor 4BC/7C

    Marsha Clements, RN, MSN/EDMarsha Clements, RN, MSN/ED

    Blinatumomab is a bispecific CD19-directed CD3 T-cell engager monoclonal antibody that was approved by the Food and Drug Administration (FDA) for treatment of patients with relapsed/refractory acute lymphoblastic leukemia (B-ALL) in December 2014. Blinatumomab was first studied at Dana-Farber/Brigham and Women's Cancer Center in a phase 1 clinical trial (# 11-501) that began in 2011 and was led by Daniel DeAngelo, MD, PhD, director of clinical and translational research in the Adult Leukemia Program at Dana-Farber/Brigham and Women's Cancer Center. This drug represented a major logistical challenge because of its prolonged infusion schedule, slow rate of infusion, and unusual side effect profile. Because of the unique aspects of this drug, it became clear that specialized training would be necessary for nursing and pharmacy staff involved in drug administration.

    The first challenge was how to organize infusion administration. Because it has a short half-life, blinatumomab infuses continuously for 28 days. While there are a few exceptions — such as 7-day cytarabine during acute myeloid leukemia (AML) induction — most anti-cancer medications do not infuse for more than 24 hours, even in a hospital setting. Therefore, significant preparation was necessary before the clinical trial began. As a nurse director for one of the Oncology units at Brigham and Women's Hospital, I worked closely with Dr. DeAngelo, research nurse practitioner Ilene Galinsky, research coordinators, and pharmacy staff to iron out the details.

    Ilene Galinsky, NP, and Daniel DeAngelo, MD, PhD, worked with Marsha Clements, RN, MSN/ED, to standardize and regionalize care for patients participating in complex clinical trials for novel therapies such as blinatomumab and CAR T-cell therapies.

    Because the bags with mixed solution of the medication contain tiny amounts of the drug (28 mcg/day or less) and each bag infuses into the patient over 48 hours, the infusion rate is very slow and patients' lines frequently clot. Blinatumomab cannot be flushed; therefore, when a venous access line clots, it can be complicated to restore patency to the line to restart the infusion.

    Another major challenge was the side effect profile of blinatumomab. The two unique adverse effects nurses needed to learn to assess and manage were cytokine release syndrome (CRS) and neurotoxicity; tumor lysis syndrome (TLS) also occurs, but was more familiar to nurses because it is seen with other drugs. Because CRS is not commonly seen with other agents and requires both recognition and special management with corticosteroids and other agents, we decided to regionalize patients receiving blinatumomab to one Oncology unit at Brigham and Women's Hospital, and to provide special training in the administration and side effect profile of this agent for the 19 nurses who work on this floor. Nurses in the outpatient setting at Dana-Farber also required instruction in the management of patients receiving this drug, because patients typically do not spend the entire 28 days in hospital and transition from inpatient to outpatient setting while the drug is still infusing – also novel in oncology. In-the-moment education and targeted communication to staff via email with specific instructions on drug administration was a key to success to help the nurses in the early days of blinatumomab. Because of blinatumomab's success in inducing remissions in patients with relapsed/refractory disease, the FDA granted it accelerated approval. When the FDA approved it, Partners P&T Committee made a decision that this drug would continue to be only administered on the one Oncology unit, to ensure safe administration and monitoring of side effects.

    Clinical trials of novel agents can be complex. There were a lot of lessons learned from blinatumomab that were subsequently successfully applied to other clinical trials, such as ongoing studies of chimeric antigen receptor T (CAR-T) cells for leukemia, lymphoma, and multiple myeloma, which also induce CRS. Patients enrolled in CAR-T cell trials are also regionalized to specific oncology units to ensure that nurses who are experts in the care of these patients are available. In addition, experience with blinatumomab paved the way for other protocols that utilize syringe pumps, a technology not typically used in our inpatient setting.

    As the programs grow, we will continue to re-evaluate our strategy. Currently, this model has been highly beneficial to patients and clinical teams. Side effects are observed quickly, and the appropriate interventions can happen in a timely manner.