Background: Daratumumab, an anti-CD38 monoclonal antibody, was first approved for the treatment of relapsed and refractory multiple myeloma (MM) in December of 2015. The approved initial infusion lasts at least 6.5 hours, second infusion for 4.5 hours and all subsequent infusions over 3.5 hours. The risk of infusion related reactions (IRRs) is very low after the second infusion, and the prolonged continued infusion time results in long days for patients. Because of our success infusing other monoclonal antibodies over shorter times, such as rituximab (Dotson et al Support Care Cancer, 2016), we hypothesized that shortening the daratumumab infusion from 3.5 hours to 90 minutes beginning with the third infusion would not increase the incidence of IRRs.
Methods: This is a single-center safety study of an accelerated daratumumab infusion in patients receiving standard of care daratumumab therapy. Patients were eligible once they received at least 2 prior doses of daratumumab, administered per standard prescribing information. Previous IRR was not an exclusion criterion. The accelerated infusion was calculated to deliver 20% of the dose over the first 30 minutes, then the remaining 80% over 60 minutes, resulting in an estimated 90 minute infusion (Table 1). Patients who tolerated the infusion well were allowed to continue the accelerated rate. Premedication regimens were allowed to be altered based on previous tolerability. Simon's two-stage optimal design was utilized to design the study based on the incidence of grade 3 or above IRR. With 80% power the design allows 7 patients to be treated in the first stage, and if no patients experienced ≥ grade 3 IRR, an additional 21 patients would be treated. Out of all 28 patients, if 2 or more experienced ≥ grade 3 IRR, the regimen would be declared as too toxic. The protocol was approved by the cancer institutional review board.
Results: Baseline characteristics are listed in Table 2. Twenty eight patients were treated with daratumumab utilizing the accelerated rate, 8 of which received the accelerated infusion with their third dose of daratumumab. The premedication regimen varied patient-to-patient and did not impact tolerability of the accelerated infusion. There were 5 patients who did not receive any steroid premedication and 3 who received reduced doses (< 12 mg) of dexamethasone. Of the 28 patients treated, there was only 1 adverse reaction - a grade 2 hypertension during which the infusion was paused for a patient that had received 10 prior infusions at standard rates. The patient received a diuretic, the infusion was resumed and subsequently increased to the accelerated rate without further incidence of hypertension. There were no grade 3 or higher IRRs. At the 4-week follow-up, all patients remaining on daratumumab treatment continued at the accelerated infusion rate.
Conclusion: An accelerated infusion rate of daratumumab delivering 20% of the dose over 30 minutes and 80% over 60 minutes is feasible and well-tolerated in patients who have received 2 prior doses of daratumumab at standard infusion rates. Starting with the third dose of daratumumab therapy, the 90-minute infusion is now standard practice at our institution.
Hofmeister: Janssen: Research Funding; Roche: Research Funding; Bristol-Myers Squibb: Research Funding; Takeda: Research Funding; Karyopharm: Research Funding; Celgene: Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Thrassos: Honoraria, Membership on an entity's Board of Directors or advisory committees.
Asterisk with author names denotes non-ASH members.
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