Comparative Analysis of Dexamethasone-Enhanced Pre-Medication in Motixafortide-Induced Hematopoietic Stem Cell Mobilization for Multiple Myeloma: A Retrospective Study

Background - Motixafortide is a high affinity CXCR4 antagonist that stimulates migration of CD34+ hematopoietic stem cells from bone marrow into peripheral blood in preparation for autologous stem cell transplantation (ASCT). The phase 3 GENESIS trial demonstrated that 88.8% of multiple myeloma patients mobilized ≥6 x 10⁶ CD34+ cells/kg in one leukapheresis procedure following the administration of one dose of motixafortide in combination with G-CSF, which led to its FDA approval in September of 2023 and our center’s adoption. Early outcomes in the development of motixafortide were associated with transient hypersensitivity and injection site reactions. Strategies to mitigate such adverse events (AEs) commonly included agents with antihistamine activity. Per the initial protocol, premedication with solely an antihistamine H1 blocker prior to administration was provided. This protocol was amended to include further premedication with an antihistamine H1 blocker, a H2 blocker, a leukotriene inhibitor and acetaminophen, which resulted in a decrease from 90.9% motixafortide-associated hypersensitivity AEs of any grade to 20%. Early on after the implementation of this protocol in our center we found unacceptable AEs with the recommended premedication, and consequently instituted a more modified protocol we have coined MF-DEX.

Methods - We performed a retrospective cohort study in adult patients diagnosed with multiple myeloma who received motixafortide for ASCT mobilization between January 1, 2024 and July 1, 2024. Our first 3 patients received the recommended premedication protocol which is oral doses of diphenhydramine 25 to 50 mg, famotidine 20 mg, montelukast 10 mg, and acetaminophen 650 mg, approximately 60 minutes before injection. Patients also received loratadine 10 mg daily beginning on the day of G-CSF initiation, 3 days prior to motixafortide. The following 5 patients received oral dexamethasone 4 mg in attempts to curtail AEs. Subsequently, 16 patients were started on MF-DEX, which consisted of starting famotidine 20 mg, montelukast 10 mg on the day of growth factor administration and continuing until 1 day after collection (5 days total), along with IV dexamethasone 8 mg added onto the standard premedications listed previously. Hypersensitivity AEs included all events recorded in MedDRA terms of urticaria, pruritus, flushing, erythema, rash, hypersensitivity or anaphylaxis. Injection site AEs were graded using CTCAE criteria.

Results - All patients that received the standard premedication had injection site reactions. Patients that received the standard premedication had 66.6% (N=2/3) grade 2 or greater injection site and hypersensitivity reactions. After the interim addition of dexamethasone 4 mg PO there was a reduction of grade 2 injection site reaction to 40% (N=2/5) and no grade 3 reactions. With the premedication strategy of MF-DEX, less patients, 5.8% (N=1/17) and 17.6% (N=3/17) had grade 2 or greater injection site and hypersensitivity reactions respectively. All patients reviewed collected 6x10 ⁶ CD34+ cells/kg stem cells with no difference seen on collection time in both groups.

Conclusions - MF-DEX decreased grade 2 hypersensitivity reactions in patients receiving motixafortide. Although patients who received the standard premedications had no grade 4 events and all AEs were manageable with supportive care, it was a clear burden to our patients and nursing staff. After adoption of MF-DEX our center has seen less hypersensitivity reactions and patient outcomes have improved.