Bortezomib 1.3 / Daratumumab 16 / Dexamethasone (20/20), Multiple Myeloma, Cycle 1

Protocol-ID: 817 V2.1 (Short), BORT1.3/DRTM16/DEXA(20/20), MM, C1

Indication(s)

Multiple Myeloma; ICD-10 C90.-, C90.0-

Protocol classification

Classification: current standard
Intensity: Standard dose
Therapy mode: Relapse therapy
Therapy intention: disease control

Cycles

Cycle length 21 days, recommended cycles: 1

Protocol sequences

CASTOR: BORT1.3/DRTM16/DEXA(20/20), MM, C1 (PID817) -|- C2-3 (PID818) -|- C4-8 (PID819) -|- C9+ (PID820)

Risks

Emetogenicity (MASCC/ESMO): minimal (<10%)
Neutropenia: moderate (11-20%)
Thrombocytopenia below 50 000/µl: very high (>41%)
Anemia Hb below 8g/dl: moderate (6-15%)
Diarrhea: CTC AE °3-4: 4%
Hypertension: CTC AE °3-4: 7%
Dyspnea: CTC AE °3-4: 4%
Fatigue: CTC AE °3-4: 5%
Neuropathy: CTC AE °3-4: 5%
Pneumonia: CTC AE °3-4: 8%

Therapy

Day	Substance	Dosage	Appl.	Inf. time	Procedure
HYD Hydration: Balanced Crystalloid Solution
Access: peripheral venous
Hydration before, during, or after antitumor therapy
1	Balanced Crystalloid Solution	500 ml	i.v.	60 min	60 min before Daratumumab (d1)

8	Balanced Crystalloid Solution	500 ml	i.v.	60 min	60 min before Daratumumab (d8)

15	Balanced Crystalloid Solution	500 ml	i.v.	60 min	60 min before Daratumumab (d15)

Day	Substance	Dosage	Solution	Appl.	Inf. time	Procedure
AP Allergy prophylaxis: Daratumumab allergy prophylaxis with dexamethasone
Access: peripheral venous
Preinfusion Medication: To reduce the risk of IRRs, premedication should be given to all patients approximately 1 hour before each infusion.
1	Dexamethasone	20 mg	NaCl 0.9% 50 ml	i.v.	5 min	60 min before Daratumumab (d1)
1	Dimetinden	4 mg	NaCl 0.9% 50 ml	i.v.	5 min	60 min before Daratumumab (d1)
1	Paracetamol	1000 mg		p.o.		60 min before Daratumumab (d1)
1	Montelukast	10 mg		p.o.		60 min before Daratumumab (d1)
8	Dexamethasone	20 mg	NaCl 0.9% 50 ml	i.v.	5 min	60 min before Daratumumab (d8)
8	Dimetinden	4 mg	NaCl 0.9% 50 ml	i.v.	5 min	60 min before Daratumumab (d8)
8	Paracetamol	1000 mg		p.o.		60 min before Daratumumab (d8)
15	Dexamethasone	20 mg	NaCl 0.9% 50 ml	i.v.	5 min	60 min before Daratumumab (d15)
15	Dimetinden	4 mg	NaCl 0.9% 50 ml	i.v.	5 min	60 min before Daratumumab (d15)
15	Paracetamol	1000 mg		p.o.		60 min before Daratumumab (d15)

Day	Substance	Dosage	Solution	Appl.	Inf. time	Procedure
CTX Medical tumor therapy: BORT1,3/DRTM16/DEXA(20/20)
Access: peripheral venous
Bortezomib, daratumumab, and dexamethasone in multiple myeloma
1,4,8,11	Bortezomib	1.3 mg/m² BSA	none	subc	Bolus	Sequence
1	Daratumumab	16 mg/kg bw	NaCl 0.9% 1000 ml	i.v.	6.5h	Sequence
Initial rate 50 ml/h, increase infusion rate by 50 ml/h every 60 minutes. Maximum infusion rate: 200 ml/h
8	Daratumumab	16 mg/kg bw	NaCl 0.9% 500 ml	i.v.	4 h	Sequence
Initial rate 50 ml/h, increase infusion rate by 50 ml/h every 60 minutes. Maximum infusion rate: 200 ml/h
15	Daratumumab	16 mg/kg bw	NaCl 0.9% 500 ml	i.v.	3.25h	Sequence
Initial rate 100 ml/h, increase infusion rate by 50 ml/h every 60 minutes. Maximum infusion rate: 200 ml/h
2,4-5,9,11-12	Dexamethasone	20 mg		p.o.		1-0-0-0
Patients with BMI below 18.5 or over 75 years of age received 20mg of dexamethasone per week.

Day	Substance	Dosage	Solution	Appl.	Inf. time	Procedure
HW Hematopoietic growth factors: G-CSF prophylaxis MM, low/intermediate risk
Access: - none -
Neutrophils < 1000/µl at start of therapy + 1 additional risk factor (Palumbo et al. 2012)
2-3,5-7,9-10,12-14,16-19	Filgrastim	5 µg/kg bw	none	subc	Bolus	1-0-0-0
Neutrophils below 1000/µl at start of therapy + 1 additional risk factor: age > 65 yrs, female gender, comorbidities, decreased immune function, body surface area less than 2m², low performance status; daily until neutrophils > 1000/µl

Day	Substance	Dosage	Appl.	Procedure
IP Infection prophylaxis: Herpes prophylaxis
Access: - none -
Aciclovir administration for herpes prophylaxis under proteasome inhibitor therapy. DGHO recommendation 07/2015
1-21	Aciclovir	400 mg	p.o.	1-0-1-0

Concomitant therapy supplements

Dexamethasone for antitumor therapy is covered by dexamethasone of allergy prophylaxis on days 1,8 and 15. The use of methylprednisolone p.o. at a low dose (less than 20 mg) or equivalent should be considered on day 3 after infusion of daratumumab. Montelukast in allergy prophylaxis is optional starting on day 8. Levofloxacin infection prophylaxis (2 x 250mg/day) is recommended for the first 3 months after initiation of therapy in patients at high risk of infection (ESMO Guideline 02/2020). In obstructive lung disease, the use of short- and long-acting bronchodilators and inhaled corticosteroids should be considered after daratumumab infusion. If no significant IRRs occur, inhaled agents may be discontinued after the first four infusions.

References

Palumbo A, Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma., N Engl J Med 2016 Aug 25;375(8):754-66 [PMID]
Richardson PG, A phase 2 study of bortezomib in relapsed, refractory myeloma., N Engl J Med 2003 Jun 26;348(26):2609-17 [PMID]
Nooka AK, Managing Infusion Reactions to New Monoclonal Antibodies in Multiple Myeloma: Daratumumab and Elotuzumab., J Oncol Pract 2018 07;14(7):414-422 [PMID]
Spencer A, Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR., Haematologica 2018 Sep 20; [PMID]
Palumbo A, How to manage neutropenia in multiple myeloma., Clin Lymphoma Myeloma Leuk 2012 Feb;12(1):5-11 [PMID]

Recommendations

07/2017: European Society for Medical Oncology
05/2020: National Comprehensive Cancer Network

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Valid since: 15.04.2021