D2.256 - Cytokine release reaction after subcutaneous daratumumab

Description of a case of desensitization to daratumumab after severe reaction in a patient with refractory multiple myeloma (MM).

We describe a 76-year-old male patient, beekeeper by profession, diagnosed with MM under treatment with daratumumab subcutaneous (sc) 8 doses weekly and then fortnightly intervals. Daratumumab sc contains polysorbate 80 and recombinant human hyaluronidase as excipients. The patient was premedicated with paracetamol, dexamethasone, dexchlorpheniramine and montelukast. During the administration of the first dose of daratumumab sc (10ml of a total of 15), he developed facial erythema, pharyngeal itching, dizziness, sweating, vomiting, tachycardia and hypotension. Drug administration was suspended. Epinephrine 0.50mg intramuscular, hydrocortisone and dexchlorpheniramine were administered. After an hour of observation, he presented shivering and fever, treated with metamizole and methylprednisolone with disappearance of symptoms. Blood tests were performed. The patient was discharged without further incident.  

A rapid drug desensitization (RDD) procedure with daratumumab iv was performed with a 1-bag protocol (12 steps). The patient was premedicated with methylprednisolone, dexketoprofen, montelukast, famotidine, dexchlorpheniramine and diazepam. 

He underwent a total of 7 cycles of desensitization with daratumumab iv without any breakthrough. After that, skin prick test with Polysorbate 80, Daratumumab (20mg/mL) and intradermal test (2mg/mL and 0.2mg/mL) were performed yielding negative results.

Total IgE was 6.74 KUA/l, specific IgE against Api m 2 of honeybee venom was negative. Post-reaction tryptase 6.8 µg/l and interleukin-6 (IL-6) 3,210 pg/ml with baseline tryptase 6.5 µg/l and IL-6 14.3 pg/ml.

To facilitate continuity of treatment, a switch from intravenous rapid drug desensitization to subcutaneous drug provocation test (DPT) was considered. Daratumumab sc DPT (1-2-4 and 8 ml at 30 minutes intervals) was tolerated without incident. 

Daratumumab, a human IgG1κ monoclonal antibody directed against apoptosis-inducing CD38 cells, is used for the treatment of relapsed/refractory MM. It produces infusion-related reactions in 26.8% of patients, mostly with the first infusion.

We describe a case of a hypersensitivity reaction following daratumumab sc with a cytokine-release phenotype. The patient underwent successful RDD with daratumumab iv and finally DPT with daratumumumab sc which was well tolerated.