Real-World Evidence Shows Safety of Rapid Infusions of Daratumumab in Multiple Myeloma

Lucio Gordan, MD

Treatment with daratumumab (Darzalex) in community clinics appeared well tolerated in patients with multiple myeloma and showed similar efficacy to that observed in clinical trials, according to a retrospective analysis investigating practice patterns of daratumumab rapid infusions.^1,2

“Rapid daratumumab infusion is an excellent treatment option, minimizing chair time while the highest standards of safety are observed for patients who may not desire or who may not be candidates for subcutaneous injection,” Lucio Gordan, MD, president and managing physician, Florida Cancer Specialists & Research Institute (FCS), told Targeted Oncology, in an interview.

Daratumumab first received FDA approval in 2016 for the treatment of patients with multiple myeloma who had received 3 or more prior lines of therapy. Today, the agent is approved in combination with other agents to treat the various subgroups of multiple myeloma. Based on prior clinical trials, treatment with the agent can lead to infusion reactions as well as respiratory events like bronchospasm, cough, and dyspnea in about half of patients treated. Although studies did show that infusion reactions were rare, the onset of the reaction and duration of treatment had a tendency to impact outcomes overall, warranting a deeper investigation around how daratumumab is administered in everyday practice.²

To conduct the retrospective study, investigators compiled data from electronic medical records owned by FCS. The project involved more than 230 physicians and included data on patient characteristics, prescription medications, and medical procedures from 534 patients who received 1 or more intravenous (IV) infusion of daratumumab. More than 99% of these patients had at least 2 visits to FCS, and 96.2% had no prior participation in a clinical trial.

Of the 534 patients whose information was reviewed, 27.5% had at least 1 rapid infusion during their first receipt of a daratumumab-containing regimen and were, therefore, eligible to be included in the analysis. The population of patients included had a median age of 73.0 years. The group was predominantly female (44.9%), and most were treated with daratumumab in either 2017 (47.6%) or 2018 (41.5%). Smaller groups were treated with daratumumab in 2016 (10.2%) and 2019 (0.7%). Following the diagnosis of multiple myeloma, daratumumab treatment was initiated in the study population within a median of 2.5 years (mean, 3.4 ± 4.3; interquartile range [IQR], 3.4). The majority of the patients had an ECOG performance status of 2 or lower (92.5%), and the population received a median of 2 (mean, 2.5 ± 2.1; IQR, 3) antineoplastic treatment regimens prior to the date their data was indexed in the FCS records. More than 12% had not received any antineoplastic treatment regimen prior to the index date though.

In terms of daratumumab treatment strategies administered to the pool of patients that were retrospectively evaluated, 34.0% received daratumumab monotherapy. The most popular daratumumab combination was daratumumab plus pomalidomide (Pomalyst), which was administered to 33.3% of the cohort.

For rapid infusions, most patients received the treatment strategy on their 11th IV infusion of daratumumab. The median duration of rapid IV infusions of daratumumab was 92 minutes (mean, 92.9 ± 8.6; IQR, 9).

The safety evaluation showed the non-infusion reaction adverse events (AEs) occurred in 10.2% of patients. These AEs were classified as general disorders and administration site conditions for 5.4% of patients, and gastrointestinal toxicities for 2.7%.

In terms of infusion reactions, 36.7% of patients had a reaction while on treatment with daratumumab during the index treatment regimen. Most patients had an infusion reaction following their second dose of daratumumab. The median number of infusion reactions experienced per patient was 2 (mean, 2.5 ± 1.3; IQR, 1). The most commonly observed infusion reactions among patients who received daratumumab were nausea (11.6%), chills (9.5%), and dyspnea (7.5%).

There were no emergency room visits associated with infusion reaction to daratumumab in the patients assessed. There were no patients who experienced an infusion reaction following a daratumumab rapid infusion.

Responses to daratumumab were noted in the retrospective analysis for 123 patients in the overall evaluable population. No stringent complete responses were achieved, and the best response was a complete response, which was observed in 4.8% of the patient population. There were also very good partial responses seen in 10.2% of patients and partial responses observed in 55.1% of patients. The overall response rate (ORR) was 91.1%, with stable disease achieved in 4.8% of patients. A low percentage of patients (2.7% ) developed disease progression. Notably, among those who received a rapid infusion on daratumumab, the ORR was 71.3%.

As for advice to oncologists who administer daratumumab by rapid infusion to patients with multiple myeloma, Gordan said to “follow protocol as outlined in the study to have reproducible results in your practice.”

_References:

_{1. Lucio Gordan, MD is lead author of an observational study on daratumumab iv rapid infusions. News release. Florida Cancer Specialists. May 24, 2021. Accessed June 2, 2021. https://bit.ly/3peuHmg}

_{2. Gordan L, Chang M, Lafeuille MH, et al. Real-world utilization and safety of daratumumab IV rapid infusions administered in a community setting: a retrospective observational study. Drugs Real World Outcomes. 2021;8(2):187-195. doi: 10.1007/s40801-020-00226-3}