Safety of ninety-minute daratumumab infusion

Abstract

Purpose Daratumumab is the first anti-CD38 monoclonal antibody of the class approved for recurrent and refractory multiple myeloma. Grade 3 and 4 Infusion-Related Reactions (IRRs) are frequent during the first and second infusions. Due to the risks associated with severe IRRs, daratumumab is systematically administered over a period of 3.5 hours. The main objective of this study was to evaluate the safety of a 90-minute daratumumab infusion from the third infusion. Patients and methods All patients who had received two or more doses of daratumumab in monotherapy or in combination with standard infusion rates were included. We excluded patients enrolled in clinical trials. For the rapid infusion protocol, 20% of the dose was administered over 30 minutes and the remaining 80% over 60 minutes. Results From April 1 to May 31, 2019, 25 patients received 53 90-minute infusions of daratumumab. Premedication included corticosteroids, antipyretics, antihistamines, and if necessary a leukotriene receptor antagonist. No grade 3 or grade 4 IRRs were observed. Conclusion From the third infusion, we found that a rapid administration of daratumumab (90 vs 210 minutes) was well tolerated and safe. It would be interesting to test this regimen from the second infusion.

Monoclonal Antibodies and Antibody Drug Conjugates in Multiple Myeloma

“…The first daratumumab infusion is usually administered in 6-h infusion and subsequent doses in 3.5-h infusion. There are however reports showing that 90-min infusion (for 3rd and subsequent doses) is as safe as the standard infusion duration [62,63]. Due to the COVID-19 pandemic, we adopted this strategy and observed no serious reactions during the second and subsequent doses (maintaining standard time of 6 h for the first infusion).…”

Daratumumab provides a survival benefit in relapsed and refractory Multiple Myeloma, independent of baseline clinical characteristics: A meta‐analysis

“…Furthermore, the treatment effect of daratumumab was consistent regardless of number of prior lines of therapy (one or two), previous lenalidomide exposure, previous proteasome inhibitor exposure, previous immunomodulatory drug exposure, refractoriness to proteasome inhibitor, refractoriness to immunomodulatory drug, or refractoriness to last line of prior therapy, indicating daratumumab‐based regimen could provide therapeutic benefit even in those with one or two previous lines of therapy and those with previous proteasome inhibitors and immunomodulatory agents 20,21 . Daratumumab plus proteasome inhibitors or immunomodulatory drugs and dexamethasone enhance direct cytotoxicity on myeloma cells, inhibited the role of regulatory T cells, as well as enhanced the activity in CD4, CD8, and NK‐cell subsets 22–24 . With increased use of frontline daratumumab therapy, more studies are needed to clarify which triplet regimens would be better for patients who have been exposed to prior lines of therapy.…”

“…20,21 Daratumumab plus proteasome inhibitors or immunomodulatory drugs and dexamethasone enhance direct cytotoxicity on myeloma cells, inhibited the role of regulatory T cells, as well as enhanced the activity in CD4, CD8, and NK-cell subsets. [22][23][24] With increased use of frontline daratumumab therapy, more studies are needed to clarify which triplet regimens would be better for patients who have been exposed to prior lines of therapy.…”

Maximizing Home Time for Persons With Cancer

“…For patients who prefer or need to attend appointments in person, data-driven simulations and lean principles can optimize the efficiency of cancer care workflows. Rapid-infusion strategies for cancer therapies beyond the more conservative dosing used in clinical trials (as have been tested previously) [40][41][42] can be studied with the truly real-world end point of door-in-door-out times that include the time needed to establish intravenous access, administer therapy, and monitor patients for postinfusion reactions. The rationale for these studies is clear: even after the COVID-19 pandemic subsides, there is no doubt that time spent at home will continue to remain an important consideration for our patients.…”