PB1995: SAFETY OF SUBCUTANEOUS DARATUMUMAB IN MULTIPLE MYELOMA: A RETROSPECTIVE MULTI-CENTER REAL LIFE EXPERIENCE

Abstract

Background: Daratumumab, an anti-CD38 monoclonal antibody, is approved for Multiple Myeloma (MM) treatment at an intravenous (IV) dosage of 16 mg/kg with high rates of infusion-related reactions (IRR; 45-56%), especially at the first infusion. However, the subcutaneous (SC) formulation has shown comparable efficacy with lower IRR risk and with shorter administration time (3-5 minutes) compared to IV daratumumab as reported in PAVO (NCT02519452), COLUMBA (NCT03277105) and PLEIADES (NCT03412565) clinical trials. Approved SC daratumumab dosage is 1800 mg, independently from patient variables including renal failure or body weight. Aims: Here, we investigate safety of SC daratumumab in different MM regimens in a multi-center real-life experience Methods: A total of 29 MM patients (Table 1) who received at least one dose of SC daratumumab at 1800 mg in any association regimen since December 2021 was included in this retrospective study. Enrolled patients were daratumumab-naïve starting directly with SC formulation combined with any association regimen displayed in Table 1. Primary end point was SC daratumumab safety, especially for IRR incidence and severity. Results: All patients received premedication with dexamethasone, paracetamol and antihistamine according to current guidelines and montelukast was used in 23 out of 29 (79%) cases. Median number of SC administrations for single patient was 3 (range 1-10), and administration time ranged from 3 to 5 minutes. One patient (3%) experienced grade III IRR in two consecutive administrations, and grade I hematological and grade I gastroenteric toxicities (diarrhea) were observed in 3 (10%; 2 thrombocytopenia and 1 neutropenia) and 1 (3%) cases Image:Summary/Conclusion: In our multicenter retrospective experience, SC daratumumab showed high safety with a very low (3%) IRR rate, even inferior to that reported in PAVO and PLEIADES trials, despite we included in our study patients with renal failure, different body weights or without montelukast premedication. Of note, IV daratumumab induced IRR especially during the first exposition, while we reported a very low IRR rate with SC daratumumab also during first administrations (median number of cycles, 3). The only patient with grade III IRRs weighted 65 kg, did not have renal failure and did not receive montelukast premedication. The patient was switched to IV daratumumab without further IRR suggesting an SC formulation excipient-related intolerance rather than daratumumab-induced reaction. However, IRR incidence was low to analyze hypothetical associations between predisposing factors and IRR insurgence. In conclusions, our real-life findings showed that SC daratumumab is very manageable with an excellent safety profile and very short administration time. Further validation on larger and prospective clinical studies are needed