Management of Infusion-Related Reactions Associated with Daratumumab Monotherapy in RRMM
Daratumumab, a novel anti-CD38 IgG1? monoclonal antibody, previously demonstrated single-agent activity in a phase 1/2 study of patients with relapsed or refractory multiple myeloma.1 A subsequent open-label, multicenter, phase 2 study was conducted to determine the optimal dose and dosing schedule for daratumumab. This study included patients randomized to daratumumab 8 mg/kg every 4 weeks or daratumumab 16 mg/kg weekly for 8 weeks, then every 2 weeks for 16 weeks, and every 4 weeks thereafter. Researchers evaluated infusion-related reactions (IRRs), which were defined to include investigator-reported events such as cough, hypersensitivity reactions, and cytokine release syndrome. IRRs were managed prophylactically with intravenous methylprednisolone 100 mg; oral paracetamol (acetaminophen) 650 to 1000 mg; and oral diphenhydramine 25 to 50 mg. Corticosteroid postinfusion medication (20 mg methylprednisone or equivalent) was given on the 2 days following daratumumab infusions to prevent delayed IRRs. Daratumumab infusion was initiated in 1000 mL at 50 mL/hr, and infusion rates were increased in the absence of IRRs/hypersensitivity. Upon onset of IRRs, infusions were temporarily interrupted or slowed.
IRRs occurred in 43% and 44% of patients in the 16-mg/kg and 8-mg/kg groups, respectively. Among patients receiving 16 mg/kg (8 mg/kg), 87% (82%) of IRRs were during the first infusion; 4% (19%) and 9% (0%) of IRRs occurred during the second and all subsequent infusions, respectively. Overall, IRRs were generally mild; most were grade 1 or 2. Grade 3 IRRs included bronchospasm, hypertension (N = 2), and anemia, dyspnea, chills, and cytokine release syndrome (N = 1). No grade 4 IRRs were reported, and no IRRs led to treatment discontinuation. Three patients were unable to finish an infusion due to an IRR but received subsequent daratumumab infusions, and remaining patients who experienced an IRR continued full-dose therapy with supportive treatment.
Researchers concluded that daratumumab-related IRRs were manageable with temporary slowing or stopping of infusion. No patient discontinued treatment due to an IRR. IRRs were most likely to occur during the first or second infusion and were predominantly of grade 1 or 2 severity. These results, which highlight the favorable safety profile of daratumumab in patients with relapsed/refractory multiple myeloma, are consistent with similar efficacy and safety findings reported in a preliminary analysis of an ongoing phase 2 study of daratumumab monotherapy in heavily pretreated patients with relapsed/refractory multiple myeloma.2
- Lokhorst HM. J Clin Oncol. 2014;32[suppl]:8513.
- Lonial S. J Clin Oncol. 2015;33[suppl]:LBA8512.