CYBORD+DARA

^† Missed doses should not be made up. For bortezomib, a minimum of 72 hours is required between doses

^αDaratumumab infusion should be administered at the appropriate initial infusion rate with incremental escalation. Subsequent infusion rate escalation or dilution reduction should only be considered if the previous infusion was well-tolerated. 

^¶Splitting the first dose over 2 days has been described (8 mg/kg days 1 and 2) and may be considered. The same premedications should be administered prior to both treatment days. See Premedication and Supportive Measures section for details.

^The dexamethasone dose should be reduced in elderly patients.

^§Dexamethasone may be given as 20mg pre-medication, on the days of daratumumab infusion, and 20mg post-medication, the days after the infusion.

REPEAT EVERY 28 DAYS

For up to 8-9 cycles, unless disease progression or unacceptable toxicity

After CYBORD is completed, refer to DARA(MNT). (Daratumumab monotherapy REPEAT EVERY 28 DAYS until disease progression or unacceptable toxicity.)

Other Supportive Care:

Also refer to CCO Antiemetic Recommendations.

Supportive care:

• HBV screening should be performed in all patients prior to starting daratumumab.

• Consider antiviral prophylaxis for herpes zoster reactivation.

• Daratumumab can interfere with cross-matching for blood transfusions; type and screen and RBC genotyping tests should be done before starting this drug.

• Patients at risk of tumour lysis syndrome should have appropriate prophylaxis and be monitored closely.

• Oral hydration is encouraged to prevent dose-related hemorrhagic cystitis.

• Prophylaxis with a proton pump inhibitor and an antibiotic (e.g. quinolone) were also used in some clinical trials.

• Use of anti-fungal mouthwash was recommended in some clinical trials.

Daratumumab Pre-medications (prophylaxis for infusion reaction):

To be given at least 1 hour prior to daratumumab infusion:

• Dexamethasone 20 mg IV/PO^*
• Oral antipyretic (e.g. acetaminophen 650-1000 mg)
• H1-receptor antagonist IV/PO (e.g. diphenhydramine 25-50 mg or equivalent)
• Famotidine 20 mg IV (or equivalent)
• Montelukast 10 mg PO^**

*_{Administer IV prior to the first infusion; Oral administration may be considered prior to subsequent infusions. Dexamethasone on the day of infusion may be given as part of pre-/post-medications for daratumumab; 20 mg IV/PO on the day of daratumumab infusion and 20 mg PO on the day after infusion. For patients receiving reduced dose dexamethasone 20 mg weekly, the entire 20 mg dose has been given prior to the daratumumab infusion in some clinical trials.}

**_{The addition of montelukast given prior to the first infusion numerically reduced the incidence of respiratory infusion reactions in the study by Nooka et al.}

Daratumumab Post-infusion Medications (prevention of delayed reactions):

• Dexamethasone 20 mg PO on the day after daratumumab infusion* 
• Consider bronchodilators (e.g. short and long acting) and inhaled corticosteroids (for patients with a history of COPD)^&***

*_{Dexamethasone on the day of infusion may be given as part of pre-/post-medications for daratumumab; 20 mg IV/PO on the day of daratumumab infusion and 20 mg PO on the day after infusion. For patients receiving reduced dose dexamethasone 20 mg weekly, the entire 20 mg dose has been given prior to the daratumumab infusion in some clinical trials.}

^&_{Consider adding an H1-receptor antagonist if the patient is at higher risk of respiratory complications.}

***_{These may be discontinued after the 4th infusion if no major IRs occurred.}

Bortezomib, cyclophosphamide and daratumumab drug monographs. Ontario Health (Cancer Care Ontario).

Nooka AK, Gleason C, Sargeant MO, et al. Managing Infusion Reactions to New Monoclonal Antibodies in Multiple Myeloma: Daratumumab and Elotuzumab. J Oncol Pract. 2018 Jul;14(7):414-22.

pCODR Expert review committee final recommendation: Daratumumab for the treatment of patients with newly diagnosed multiple myeloma. Aug 29, 2019.

Reeder CB, Reece DE, Kukreti V, et al.  Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia 2009; 23: 1337–41.

Yimer H, Melear J, Edward Faber E, et al. Lyra: a phase 2 study of daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (Cybord) in newly diagnosed and relapsed patients (Pts) with multiple myeloma. Blood 2018;132 (Supplement 1):152.