Retrospective review of accelerated daratumumab administration

Abstract

Daratumumab is an anti-CD38 monoclonal antibody approved for multiple myeloma. The initial infusion is administered over a median of 7.5 hours with subsequent infusions given over 3 to 4 hours. Studies show high incidence of infusion related reactions (IRRs) with the initial dose which decreases with subsequent infusions. Accelerated 90 minute daratumumab infusions following the second dose of standard administration are widely accepted in practice including at Beth Israel Deaconess Medical Center (BIDMC) despite limited data from small safety studies. The objective of this study is to evaluate the safety of accelerated daratumumab administration compared to standard administration. The primary outcome is the incidence of common terminology criteria for adverse events (CTCAE) version 5.0 grade 1 or higher for IRRs in accelerated and standard infusions. Secondary outcomes include non-IRR adverse events and amount of supportive care medications used pre- and post- and during accelerated and standard infusions. A total of seventy five patients received a daratumumab infusion between November 2015 and August 2019. There were a total of 420 daratumumab infusions evaluated, 317 (75.5%) were standard infusions of which 152 infusions were standard infusions that preceded an accelerated infusion. There were a total of 103 (24.5%) accelerated infusions. IRRs occurred in a total of 38 (9%) of the infusions with CTCAE grade 2 reactions occurring in total of 21 (5%) infusions and grade 1 occurring in 15 (3.6%) infusions. Overall accelerated daratumumab administration is safe and well tolerated when given following at least two standard infusions.

Safety and feasibility analysis of rapid daratumumab infusion in Chinese patients with multiple myeloma

“…Our findings confirmed the results of the Barr et al 9 . study, indicating the safety and feasibility of our regimen, which is consistent with the results of other studies 9–17 . We found that accelerating the DARA infusion rate for subsequent infusions after the second infusion reduces the infusion time, and IRRs are less common.…”

“…In a comprehensive comparison of all other rapid infusion literature, [9][10][11][12][13][14][15][16][17] our study protocol showed a low rate of adverse events and low severity of IRRs with 738 rapid DARA infusions. Hamadeh et al 10 developed a model for analyzing 53 patients who received DARA infusions.…”

“…Barr and colleagues were the first to report that 28 MM patients receiving 90 min of rapid infusion had no infusion reactions, and only one patient experienced a grade 2 hypertension event. 9 Other studies [10][11][12][13]15,16 have also concluded that this regimen may be feasible. Bonello et al 15 reported that when a 90-min rapid infusion regimen was used for DARA infusion into 134 MM patients, 7 (5%) developed grade 1 and 2 IRRs.…”

“…MM is common in elderly patients who are in poor physical condition and have many comorbidities, and prolonged infusion can easily cause fatigue, anxiety, irritability, and other discomfort. Many studies [9][10][11][12][13][14][15][16][17] have shown that the majority of DARA IRRs occur during the first and second infusions, with a significantly lower incidence of IRRs occurring during subsequent infusions.…”

“…MM is common in elderly patients who are in poor physical condition and have many comorbidities, and prolonged infusion can easily cause fatigue, anxiety, irritability, and other discomfort. Many studies 9–17 have shown that the majority of DARA IRRs occur during the first and second infusions, with a significantly lower incidence of IRRs occurring during subsequent infusions. If the infusion rate is accelerated and the infusion time is shortened after the second infusion, patient comfort can be improved and patient anxiety can be reduced.…”