Daratumumab in combination with cyclophosphamide, bortezomib, and dexamethasone (CyBorD) for treating light chain (AL) amyloidosis based on the ANDROMEDA study:

Dosing Schedule for Daratumumab-CyBorD

– Daratumumab (DARA SC) Administration:

– Weeks 1 to 8: Administer daratumumab subcutaneously once weekly.

– Weeks 9 to 24: Administer daratumumab every two weeks.

– Thereafter: Administer daratumumab every four weeks for up to two years[5][6].

– Cyclophosphamide, Bortezomib, and Dexamethasone (CyBorD) Administration:

– Cyclophosphamide: 300 mg/m² orally or intravenously on Days 1, 8, and 15 of each 28-day cycle.

– Bortezomib: 1.3 mg/m² subcutaneously on Days 1, 8, and 15 of each 28-day cycle.

– Dexamethasone: 40 mg orally or intravenously weekly[5].

DOSAGE AND ADMINISTRATION (PROTOCOL)

Daratumumab 1800 mg will be administered subcutaneously through a syringe by a manual push over approximately 5 minutes. Daratumumab will be administered weekly for the first 8 weeks (2 cycles), then every 2 weeks for 4 cycles (Cycles 3-6), and then every 4 weeks until progression of disease or subsequent therapy for a maximum of 2 years from the start of the study.

Subjects will receive 300 mg/m 2 cyclophosphamide (maximum weekly dose 500 mg) as an oral or IV weekly dose and 1.3 mg/m 2 bortezomib as an SC injection weekly (Days 1, 8, 15, 22) in every 28-day cycle for a maximum of 6 cycles.

Dexamethasone will be administered at a total dose of 40 mg weekly (ie, Days 1, 8, 15, 22). On days of daratumumab dosing, subjects in Treatment Arm B will receive 20 mg on the day of daratumumab dosing as premedication and 20 mg on the day after daratumumab dosing.

On weeks that daratumumab is not administered, or for subjects randomized to Treatment Arm A, dexamethasone is to be given 40 mg weekly on a single day or divided into 2 days.

Associated Toxicities

– Infusion-Related Reactions (IRRs): These are common during the first infusion but decrease with subsequent doses. Symptoms may include respiratory issues, fever, and chills[4][8].

– Hematologic Toxicities: Myelosuppression, leading to anemia, neutropenia, and thrombocytopenia, is possible, increasing the risk of infections[1][6].

– Infections: Respiratory infections are particularly common and should be monitored closely[6].

– Other Side Effects: Fatigue, nausea, diarrhea, peripheral edema, and upper respiratory tract infections have been reported[1][4].

 Management of Toxicities

– Pre-medication: Administer antihistamines, antipyretics, and corticosteroids before daratumumab infusions to reduce the risk of IRRs[4].

– Monitoring: Regular monitoring of blood counts and organ function is essential to manage hematologic toxicities and organ-related side effects[2].

– Infection Prophylaxis: Consider prophylactic antibiotics and vaccinations to prevent infections[2].

 

Citations:

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998921/

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855501/

[3] https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761145s002lbl.pdf

[4] https://www.cancercareontario.ca/en/system/files_force/daratumumab.pdf?download=1

[5] https://ashpublications.org/blood/article/136/1/71/454281/Daratumumab-plus-CyBorD-for-patients-with-newly

[6] https://ashpublications.org/blood/article/140/22/2317/485153/Daratumumab-in-AL-amyloidosis

[7] https://www.darzalexhcp.com/pdfs/dosing-and-administration-guide-faspro.pdf

[8] https://www.medicalnewstoday.com/articles/drugs-darzalex-side-effects