Characteristics of Daratumumab Reactions in Patients Who Transitioned from Intravenous Daratumumab to Subcutaneous Daratumumab
Authors: Kim Chang Kun , Douglass Lindsey , Gustafson Beth , Begemann Madeline E , Cossor Furha I. , Gupta Vinay , Raza Shahzad 
Published: November 2021

Abstract
Introduction
Daratumumab based therapy has become standard of care in the treatment of Multiple Myeloma and Systemic Light chain Amyloidosis. The intravenous (IV) infusion of daratumumab is associated with a high rate of infusion-related reactions necessitating use of rescue medications and prolonged chair time. The Phase 3 COLUMBA trial reported non-inferiority of the subcutaneous (SC) daratumumab as compared to IV formulation with significantly reduced rates of daratumumab reactions for new-start patients. However, there is limited data on the characteristics of reactions in patients transitioning between formulations.
Methods
This single center retrospective chart review was performed on consecutive patients who previously received IV daratumumab but subsequently converted to SC daratumumab between June 2020 and June 2021. In this study, severity of allergic reactions and potential predictors of SC daratumumab reaction were assessed.
Results
Of the 45 patients who received SC daratumumab during the study period, a total of 13 patients had previously received IV daratumumab. All patients were premedicated per package insert guidelines and institutional standard of care. Patients were predominately Caucasian (77%), Male (84.6%), and undergoing therapy for Multiple myeloma (69%) and AL Amyloidosis (31%). A mean of 19 doses of IV daratumumab were administered prior to transition to SC formulation. The majority of patients (53.8%) transitioned to SC daratumumab had previously reacted to IV daratumumab. All IV daratumumab reactions occurred during the first infusion. Two patients had experienced Grade 3 reactions to IV daratumumab, requiring inpatient observation to complete the initial infusion but tolerated subsequent doses.
Of the 13 patients transitioned to SC daratumumab, two patients (15.4%) experienced daratumumab reactions. Patient 1 had a history of grade 3 IV daratumumab reaction to the first infusion and experienced a Grade 2 reaction at 3 hour 50 minutes with symptoms of cough, shortness of breath, palpitations, itching, and myalgia to the first SC daratumumab dose. Subsequent SC daratumumab doses were tolerated without adverse reactions. The other patient had a history of grade 2 IV daratumumab reaction who noted worsening weakness and diarrhea in the first several days post-injection with the new formulation, and ultimately transitioned back to the IV formulation.
Conclusion
Although SC daratumumab is well tolerated in patients previously treated with IV daratumumab, patients with history of prior first IV daratumumab infusion reactions are still at increased risk of early or delayed daratumumab related reactions with first time exposure to SC daratumumab.

Disclosures
Gupta: Deva Oncology: Consultancy. Raza: Amgen: Honoraria, Speakers Bureau; drrx, acasti, amicus, abbot: Other: previous stock holder (currently does not hold these stocks); Gilead: Current holder of individual stocks in a privately-held company; Janseen: Honoraria, Speakers Bureau; Takeda: Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite: Honoraria, Membership on an entity's Board of Directors or advisory committees; Moderna , Biontec, Stryker: Current holder of individual stocks in a privately-held company; novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Speakers Bureau.