Optimizing Care: Discontinuing Medications Prior to Daratumumab and Hyaluronidase-Fihj Subcutaneous Injection (OMIT)

Introduction

Intravenous daratumumab (DARA IV) is generally well tolerated, but it is commonly associated with infusion-related reactions (IRRs). Per prescribing information (PI), the manufacturer recommends pre-infusion medications with diphenhydramine, acetaminophen, and a corticosteroid prior to each infusion to prevent IRRs (Darzalex™ [PI]; 2019, DarzalexFaspro™ [PI]; 2020). However, in our experience the incidence of IRRs is significantly lower after the first three infusions, if they were well tolerated. Therefore, to decrease pill burden and overmedicating the patient at Cedars-Sinai Medical Center (CSMC), the pre-infusion medications for the fourth and subsequent infusions are discontinued. The new subcutaneous (SQ) formulation daratumumab and hyaluronidase- fihj (DARA SQ) has an even lower incidence of IRRs compared to the IV formulation, 12.7% versus 34.5%, of all grades and 1.5% versus 5.4% of grade 3 respectively (Mateos MV., et al. Lancet; 2020). Given the lower risk of IRRs, CSMC recommends discontinuing pre-medications after the third DARA SQ injection, or never starting them if the patient had previously tolerated three or more DARA IV infusions and is now being switched to the SQ formulation. This strategy has been our approach and to date our patients have tolerated their infusions and/or injections. Unfortunately, there is no published literature to guide clinicians, so institutions have different approaches based upon their own anecdotal experiences or hearsay.

Methods

A single-center, retrospective chart review was performed on patients from a single physician who have received at least one dose of DARA SQ from June 1 through July 22, 2020 at CSMC. A total of 63 patients were screened, one patient was excluded because she required diphenhydramine with each treatment. Data collected included number of DARA SQ doses given without pre-medications, diagnosis, previous treatment with DARA IV, time since last DARA IV treatment, previous IRRs to DARA IV (graded as per CTCAE version 5.0), IRRs to DARA SQ, number of SQ doses, corticosteroids use, and if the patients had any pre-existing pulmonary conditions. The primary objective was to review the incidence of IRRs in our patients following the omission of pre-medications after the third DARA SQ injection.

Results

A total of 81 doses of DARA SQ were administered to 62 patients. All treatments were well tolerated, and no systemic IRRs were documented. Only one patient had a localized reaction, characterized as erythema around the injection site. Most of the patients were diagnosed with multiple myeloma (94%), one patient had smoldering myeloma, and three patients were diagnosed with amyloidosis. Most patients were previously treated with DARA IV (77%) with a median time since last IV dose of 28 days (range, 7 – 59 days). 15 of these patients had a history of mild to moderate IRRs to DARA IV: 4 were grade 1 and 11 were grade 2. The most common corticosteroid treatment was dexamethasone 20 mg weekly, ranging from 4 mg twice weekly to 40 mg weekly. 18 patients did not receive corticosteroids as part of their treatment regimen, nor as a pre-treatment medication. The majority of the patients (85%) did not have a pre-existing documented pulmonary condition.

Conclusion

All our patients were able to safely receive DARA SQ without pre-medications with acetaminophen and diphenhydramine beginning with the fourth dose. Furthermore, 18 patients stopped corticosteroids with subsequent injections and were able to tolerate treatment without any IRRs. Clinicians should take into consideration that corticosteroids are given not solely as pre-medication, but also as a treatment for multiple myeloma. Therefore, if the only purpose of corticosteroids is the prevention of IRRs, their administration can be avoided. A previous reaction to DARA IV did not increase the risk of IRRs to DARA SQ. Diphenhydramine can cause drowsiness which can impair a patient’s ability to drive home after their treatment; corticosteroids can cause insomnia, stomach upset, and hyperglycemia. By omitting unnecessary pre-medications, these unwanted adverse drug effects can be avoided. This study demonstrates that we can safely discontinue DARA SQ pre-medications if a patient tolerates the initial three treatments of IV or SQ daratumumab.