MADRID – The high rate of infusion-related reactions at first daratumumab infusion may be related to treatment duration, based on data from the CASTOR and POLLUX studies presented at the European Society for Medical Oncology Congress.
Infusion-related reactions occur in half of relapsed or refractory multiple myeloma patients who receive daratumumab, but nearly all reactions are grade 2 or less and rarely lead to treatment discontinuation, reported Philippe Moreau, MD, of University Hospital, Nantes, France.
“In the two phase 3 trials, CASTOR and POLLUX, infusion-related reactions occurred in 45% and 48% of patients, respectively. Of these, 98% and 96%, respectively, occurred during the first infusion,” he said. Treatment duration was 7 hours for first infusion vs. 4 hours and 3 hours for the second and third infusions, respectively. Grade 3 infusion-related reactions occurred in 5.3% and 8.6% of patients in CASTOR and POLLUX, respectively. No grade 4 infusion-related reactions were observed in either trial.
(In CASTOR [NCT02136134], daratumumab was combined with bortezomib and dexamethasone. In POLLUX [NCT02076009], it was combined with lenalidomide and dexamethasone. Based on improvements in progression-free survival relative to the background drugs alone, daratumumab was approved for relapsed or refractory multiple myeloma.)
All patients in the trials received some form of preinfusion medications. These included 650-1,000 mg of paracetamol by intravenous or oral administration, 25-50 mg of diphenhydramine, 10 mg of montelukast, and 20 mg of dexamethasone. Patients thought to be at high risk of respiratory complications were candidates for postinfusion medications such as diphenhydramine or a short-acting beta agonist. However, only about 10% of high-risk patients received these therapies, so the impact of this potentially preventive approach is not clear, Dr. Moreau said.
In grade 1 reactions, Dr. Moreau recommended that infusions be paused at the first sign of an infusion-related reaction and then restarted at half the infusion rate when the condition is considered stable. Daratumumab treatment should be withdrawn in grade 2 or higher infusion-related reactions associated with laryngeal edema or grade 2 or higher bronchospasm that does not respond to systemic therapy and resolves within 6 hours of onset.
In grade 3 infusion-related reactions, the recommendation is to stop the daratumumab infusion and closely observe the patient. The infusion should be restarted only if the severity drops to grade 1. Again, the rate of infusion after the interruption should be half the rate provided prior to the infusion-related reaction. Therapy should be withdrawn if the infusion-related reaction recurs for a second time, according to Dr. Moreau.
Infusion-related reactions involving the upper respiratory tract – such as dyspnea, cough, bronchospasm, or throat irritation – may be related to the physiologic function of CD38, Dr. Moreau said. For this reason, grade 3 upper respiratory-related events deserve close attention and persisting symptoms warrant halting treatment.
The evidence is “reassuring” that the majority of infusion-related reactions are confined to the first infusion, said the ESMO-invited discussant, Evangelos Terpos, MD, PhD, of the University of Athens. He noted that the specific treatment recommendations outlined by Dr. Moreau could be helpful for minimizing nuisance infusion-related reactions as well as reducing the risk of more serious infusion-related reactions, particularly those involving respiratory events.
Prophylactic strategies for infusion-related reactions are particularly important in patients with risk factors for respiratory complications, Dr. Terpos added.