The results of a small, single-arm study conducted at the Ohio State University indicate that adminis­tering Darzalex using a time-saving 90-minute in­fusion protocol can be safe.

No patients in the study ex­peri­enced severe in­fusion-related reac­tions, and there was only one mild reac­tion in a patient who had no further reac­tions during sub­se­quent in­fusions at the 90-minute rate.

The faster Darzalex (dara­tu­mu­mab) in­fusion rate tested in the study is two hours shorter than the standard 3.5 hour rate. Patients in the study were receiving their third, or sub­se­quent, Darzalex in­fusions.

Infusion-related reac­tions are allergy-like responses, such as dif­fi­culty breath­­ing or sinus congestion, that can occur during drug in­fusions. These reac­tions are often mild, but they can be severe.

Given the results of the Ohio State study, a number of myeloma treat­ment centers in the United States either are already using the faster in­fusion protocol, or planning to do so in the near future.

Background

Darzalex belongs to a class of drugs known as mono­clonal anti­bodies. It is the first drug in that class ody approved in the United Status for the treat­ment of multiple myeloma (see related Beacon news). Darzalex binds to a protein known as CD38, which is commonly found on the surface of myeloma cells. Once bound to a myeloma cell, Darzalex attacks the cell while also signaling the patient's immune sys­tem to act against the cell.

Infusion-related reac­tions can occur during the admin­istra­tion of Darzalex. The reac­tions, which can in­clude shortness of breath, sinus congestion, coughing, elevated blood pressure, or chills, are particularly likely to occur during a patient's first Darzalex in­fusion. An analysis of data from two large Darzalex clin­i­cal trials, for example, found that 96 per­cent of the recorded in­fusion-related reac­tions occurred during patients' first Darzalex treat­ments.

To avoid poten­tially serious in­fusions reac­tions, the rec­om­mended durations for a patient's first, second, and third (and sub­se­quent) Darzalex in­fusion have been set at 6.5, 4.5, and 3.5 hours, re­spec­tive­ly. In addi­tion, it is rec­om­mended that patients receive various anti-inflammatory medications, such as antihistamines and steroids, right before each Darzalex in­fusion to de­crease the likelihood of in­fusion-related reac­tions.

The authors of the current study note, how­ever, that pre­vi­ous research in patients with non-Hodgkin's lym­phoma found that the mono­clonal anti­body Rituxan (rituximab) can be admin­istered safely in as little as an hour in patients receiving their second or sub­se­quent in­fusion. The researchers there­fore speculated that it also might be safe to use a more rapid Darzalex in­fusion protocol in patients who have had two prior in­fusions of the drug.

Study Design

For their study, the researchers from the Ohio State University first recruited seven multiple myeloma patients who had to have received at least two Darzalex in­fusions at standard in­fusions rates. If none of those seven patients ex­peri­enced severe in­fusion-related reac­tions at the accelerated in­fusion time, 21 addi­tional patients would be recruited. If two or more of the 28 patients ex­peri­enced severe in­fusion-related reac­tions, the accelerated in­fusion would be con­sidered too toxic.

All study par­tic­i­pants received the first 20 per­cent of their in­fusion over 30 min­utes, and the remaining 80 per­cent of the in­fusion over 60 min­utes. Vital signs were taken before the start of the in­fusion, every 15 min­utes during the first 60 min­utes of the in­fusion, and at the end of the in­fusion. For a patient's first in­fusion at the accelerated rate, vital signs were also taken 30 min­utes after completion of the in­fusion to check for delayed in­fusion-related reac­tions.

Since none of the first seven patients ex­peri­enced severe in­fusion-related reac­tions, the addi­tional 21 multiple myeloma patients were recruited as planned for a total of 28 study par­tic­i­pants.

The median patient age was 67 years old. The patients had received a median of five prior Darzalex in­fusions.

Premedication in­cluded acetaminophen (Tylenol) (96 per­cent of patients), antihistamines (100 per­cent), the steroid dexa­meth­a­sone (82 per­cent), and the anti-inflammatory Singulair (montelukast) (29 per­cent).

Approximately 40 per­cent of the study par­tic­i­pants had ex­peri­enced in­fusion-related reac­tions during their first Darzalex in­fusion.

Study Results

None of the 28 patients treated with the accelerated Darzalex in­fusions ex­peri­enced any severe in­fusion-related reac­tions.

There was one mild in­fusion reac­tion, which was a case of hyper­tension in a patient with a history of hyper­tension. The in­fusion was halted and the patient received a diuretic, which re­solved the hyper­tension. The patient's in­fusion was resumed at their pre­vi­ously tolerated in­fusion rate, and sub­se­quent in­fusions were at the accelerated rate, which the patient tolerated.

At the four-week follow-up, all patients con­tinued treat­ment at the accelerated in­fusion rate without any addi­tional side effects.

Adoption of the More Rapid Infusion Protocol

A number of myeloma treat­ment centers in the United States are either using the new 90-minute Darzalex in­fusion protocol, or planning to do so in the near future.

The Beacon reached out to myeloma specialists at nine U.S. treat­ment centers to find out about their current or planned use of a more rapid Darzalex in­fusion protocol. Of those nine centers,

• Five centers (Cleveland Clinic, Memorial Sloan Kettering, Moffitt, Ohio State, and Winship / Emory) already are using the faster infusion protocol
• One center (Mayo Clinic) plans to start using the protocol in the next several months
• One center (University of Pennsylvania) plans to pilot the new protocol very soon
• One center (Dana-Farber) is reviewing the new protocol and considering implementing it
• One center (Seattle Cancer Care Alliance) expects to continue with the currently recommended infusion times.

The more rapid in­fusion protocol is being used, or will be in use, in patients who have received two or more prior Darzalex in­fusions using standard in­fusion rates. In most, if not all, cases, the more rapid protocol being used is the same as the one in the Ohio State study.

For more in­­for­ma­tion, in­clud­ing im­por­tant details about pre­medi­ca­tion protocols and patient exclusion criteria used with the faster in­fusion rate, please see the study by Barr, H. et al., “Ninety-minute dara­tumumab in­fusion is safe in multiple myeloma,” in Leukemia, March 31, 2018 (full text of article; subscription or purchase required) and the related American Society of Hematology meeting abstract and poster (PDF) (poster courtesy of Dr. Craig Hofmeister, Winship Cancer Center, Emory University).