Shield or Security Blanket? Premedication Use With Calaspargase‐Pegol

To the Editor, Asparaginase therapy is essential for the treatment of acute lymphoblastic leukemia (ALL) [1]. In December 2022, the manufacturer of pegaspargase introduced calaspargase-pegol, a different formulation of pegylated asparaginase. With the addition of calaspargase-pegol to the market, the manufacturer required all pediatric patients 1 month to <22 years of age to use the new formulation. One of the most common and serious adverse events with pegylated asparaginase therapy is hypersensitivity reaction, and several studies have looked at mitigating this side effect using premedications [2-4]. To date, most data for premedications (both positive and negative) have been specific to pegaspargase. However, rates of hypersensitivity reactions with calsapargase-pegol are high—with one institution reporting rates higher than pegaspargase [5]. In October 2023, our institution began adding famotidine, acetaminophen, and intravenous (IV) fluids to Y-in to the infusion for patients receiving calaspargase-pegol (all infusions are run over two hours at our institution, both before and after this change). These premedications were in addition to ondansetron, steroids, and cetirizine previously given to patients prior to infusion. This was in an effort to decrease infusion reactions seen with calaspargase-pegol and aligned with an update to the package insert that specifically recommended premedication with acetaminophen, histamine-1 (H-1) receptor blocker, and H-2 receptor blocker [6]. At the time of the change, a plan was made to review reaction rates and determine if premedications impacted hypersensitivity reactions. Two hundred thirty-four total calaspargase-pegol administrations, representative of 79 individual patients, were reviewed. Fifteen patients had a hypersensitivity reaction requiring transition to Rylaze therapy (15 of 79 patients = 19%). In the overall cohort of patients who reacted (n = 15), eight patients (53.33%) received all six premedications. Of the 15 patients who reacted to calaspargase-pegol and required transition to Rylaze: 12 patients (80%) reacted to the second dose, and three patients reacted to their third dose. No patients reacted to the first dose or any dose after number 3 (dose 4 and beyond if applicable). Of the patients who reacted to the second dose of calsapargase-pegol (n = 12), seven (58.33%) received all six premedications and five patients (41.66%) did not receive all six premedications (specifically did not receive the H2 receptor antagonist, acetaminophen, or fluids at the Y-site). Of the patients who reacted to the third dose of calsapargase-pegol (n = 3), one patient (33.3%) received all six premedications; two patients (66.7%) did not receive all six premedications (specifically did not receive the H2 receptor antagonist, acetaminophen, or fluids at the Y-site). Administrations were further broken down by excluding first doses of any asparaginase product as the likelihood of reacting to a first dose is incredibly low [4]. There were 172 administrations, representative of 63 patients, that were not the first dose of any asparaginase product. Of note, some of these patients may have received fewer than six premedications at one administration and later the full number of administrations. Seventy-five (43.6%) of the administrations, representing 35 patients (55%), included all six premedications. Nine of the 35 patients (25.7%) who received all six premedications reacted to calaspargase-pegol and required transition to Rylaze. Of the 97 administrations, representing 43 patients, who did not receive all six premedications, seven patients (16.3%) reacted and required transition to Rylaze. In our institutional review, the addition of acetaminophen, famotidine (H2 receptor antagonist), and fluids did not seem to impact rates of hypersensitivity reaction. The addition of these medications increases medication burden at infusion appointments without benefit. Further, multisite studies can evaluate the overall appropriateness of the addition of these premedications, and if changes to package insert recommendations may be warranted. The author declares no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.