Evaluation of Reduced Observation Times for Subcutaneous Administration of Daratumumab and Hyaluronidase in Patients With Multiple Myeloma

Presenting Author: Brian Primeaux, PharmD, BCOP, MD Anderson Cancer Center, Houston, TX

Co-Authors: Arsemen Brown, PharmD, Alisha Desai, PharmD, Elizabeth Graver, PharmD, Amy Zheng, PharmD, and Sandra Horowitz, PharmD, MD Anderson Cancer Center, Houston, TX

BACKGROUND: Daratumumab is an anti-CD38 monoclonal antibody that can be given subcutaneously (SC) when formulated with hyaluronidase for previously untreated and relapsed/refractory multiple myeloma. Infusion-related reactions are often observed with daratumumab, and premedication is required before administration. However, the manufacturer provides little guidance on observation times and monitoring after daratumumab/hyaluronidase SC administration. Our institution originally adopted observation times similar to research protocols conducted within the institution of 6 hours for the first dose, 2 hours for the second dose, and 15 minutes for subsequent doses of daratumumab/hyaluronidase SC. Since then, publications have demonstrated the appropriateness of shorter monitoring periods of varying degrees. Due to these data, observation times after daratumumab/hyaluronidase SC administration were reduced to 2 hours for the first dose, 30 minutes for the second dose, and 15 minutes for subsequent doses.

OBJECTIVES: The primary objective was to determine if reduced observation times for daratumumab/hyaluronidase SC affected the rates of infusion reactions. The secondary objective was calculation of chair time saved.

METHODS: All daratumumab/hyaluronidase SC administrations during a 2-year time frame (February 4, 2021, to May 1, 2023) were collected via Pharmacy Analytics. Administrations were separated based on preintervention and postintervention. Preintervention was defined as SC daratumumab administrations with an observation time of 6 hours after the first dose and 2 hours after the second dose. Postintervention was defined as SC daratumumab administrations with an observation time of 2 hours after the first dose and 30 minutes after the second dose.

RESULTS: A total of 203 patients were included, with 87 in the preintervention group and 116 in the postintervention group. No clinically significant differences were found in rates of reaction with reduced observation time with daratumumab/hyaluronidase SC. Reactions were similar, with 6% for dose 1 and 1% for dose 2 for the preintervention group, and 4% for dose 1 and 3% for dose 2 in the postintervention group. The most common reactions were hypertension followed by shortness of breath. For the 116 patients in the postintervention group, reduced observation time saved nearly 27 days of chair time.

CONCLUSION: The results of this study show there was no clinically significant difference in infusion-related reactions when comparing longer observation times to shortened observation times. Shortened observation times resulted in a significant amount of chair time saved. Based on the results of this study, it is recommended to continue the shortened observation time after administering daratumumab/hyaluronidase SC.

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