Download Daratumumab Monograph

Daratumumab (interim monograph)
DRUG NAME: Daratumumab
SYNONYM(S): HuMax CD381
COMMON TRADE NAME(S): Darzalex®
CLASSIFICATION: miscellaneous
Special pediatric considerations are noted when applicable, otherwise adult provisions apply.
MECHANISM OF ACTION:
Daratumumab is an IgG1ĸ human monoclonal antibody produced in a Chinese hamster ovary cell line.
Daratumumab binds to the transmembrane glycoprotein CD38 thus inhibiting the growth of CD38 expressing tumour
cells. Mechanism for cell lysis may include direct induction of apoptosis as well as complement-mediated
cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cellular phagocytosis. CD38 is
1-4
highly expressed on myeloma cells, but is expressed at low levels on normal lymphoid and myeloid cells.
USES:
Primary uses:
3
Multiple myeloma
Other uses:
*Health Canada approved indication
SPECIAL PRECAUTIONS:
Contraindications:
3
• history of hypersensitivity reaction to daratumumab or Chinese hamster ovary cell proteins
Caution:
• severe infusion reactions are sometimes reported; pre-medicate with IV corticosteroids, oral antipyretics, and
3
oral/IV antihistamines one hour prior to each infusion. See paragraph following Side Effects table.
• antiviral prophylaxis is suggested to prevent herpes zoster reactivation; initiate within 1 week of starting
3
daratumumab and continue for 3 months following treatment
3,5
• daratumumab interferes with antibody screening tests and cross matching; see Interactions
SIDE EFFECTS:
The table includes adverse events that presented during drug treatment but may not necessarily have a causal
relationship with the drug. Because clinical trials are conducted under very specific conditions, the adverse event
rates observed may not reflect the rates observed in clinical practice. Adverse events are generally included if they
were reported in more than 1% of patients in the product monograph or pivotal trials, and/or determined to be
clinically important.
ORGAN SITE
SIDE EFFECT
Clinically important side effects are in bold, italics
blood and lymphatic
system/ febrile
neutropenia
anemia (45%, severe 19%)
lymphopenia (72%, severe 40%)
neutropenia (60%, severe 20%)
BC Cancer Agency Cancer Drug Manual
Developed: 25 May 2016
Revised: 1 July 2016
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Daratumumab interim monograph
Daratumumab (interim monograph)
ORGAN SITE
SIDE EFFECT
Clinically important side effects are in bold, italics
gastrointestinal
general disorders and
administration site
conditions
immune system
infections and
infestations
metabolism and nutrition
musculoskeletal and
connective tissue
nervous system
respiratory, thoracic and
mediastinal
thrombocytopenia (48%, severe 18%)
6
emetogenic potential: low
constipation (15%)
diarrhea (16%, severe 1%)
nausea (27%)
vomiting (14%)
7
extravasation hazard: none
chills (10%)
fatigue (39%, severe 2%)
3,8
physical health deterioration (3%)
pyrexia (21%, severe 1%)
infusion reaction; initial infusion (48%, severe 3%); second infusion (5%); subsequent
3,8
infusions (4%) ; see paragraph following Side Effects table
8
herpes zoster (3%)
nasopharyngitis (15%)
pneumonia; including streptococcal and lobar pneumonia (11%, severe 6%)
upper respiratory tract infection (20%, severe 1%)
appetite decrease (15%, severe 1%)
arthralgia (17%)
back pain (23%, severe 2%)
musculoskeletal chest pain (12%, severe 1%)
pain in extremity (15%, severe 1%)
headache (12%, severe 1%)
cough (21%)
dyspnea (15%, severe 1%)
nasal congestion (17%)
vascular
hypertension (10%, severe 5%)
Adapted from standard reference3 unless specified otherwise.
Serious adverse reactions are reported in 33% of patients, most frequently pneumonia, general physical health
3
deterioration, and pyrexia. Grade 3-4 laboratory abnormalities are reported in more than 10% of patients.
Approximately half of all patients experience an infusion-related reaction. Most reactions occur during the first
infusion, however reactions are reported with all infusions. None of the reactions with second or subsequent
infusions were rated as Grade 3 or higher severity. Reactions typically occur during the infusion itself or within 4
hours after the infusion is completed. Common symptoms include nasal congestion, cough, chills, allergic rhinitis,
larynx or throat tightness/irritation, dyspnea, and nausea. Severe symptoms include bronchospasm, hypoxia,
3,8
dyspnea, and hypertension. Premedicate with intravenous corticosteroid, oral antipyretic, and oral/intravenous
antihistamine one hour prior to every infusion of daratumumab. Steroid dose may be decreased following the second
infusion. Post-infusion oral corticosteroids are recommended for all patients on days 2 and 3 of each cycle to prevent
delayed reactions. Follow incremental infusion rate closely for each cycle and monitor patients during the entire
infusion. Interrupt daratumumab for infusion reactions of any grade/severity and manage symptoms. For patients
with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion. When re-challenging,
rd
permanently discontinue daratumumab following the 3 occurrence of a Grade 3 reaction. Permanently discontinue
3
daratumumab for any life threatening (Grade 4) reaction.
BC Cancer Agency Cancer Drug Manual
Developed: 25 May 2016
Revised: 1 July 2016
©
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Daratumumab (interim monograph)
Patients with a history of obstructive pulmonary disorder may require additional inhaled corticosteroids and
bronchodilators post-daratumumab infusion to manage respiratory complications. Post-infusion medications may be
3,5,8
discontinued If no major infusion reactions are reported following the first four infusions.
INTERACTIONS:
AGENT
EFFECT
MECHANISM
MANAGEMENT
Coombs test (Indirect
3,5
Antiglobulin Test)
false positive test result for
up to 6 months after last
infusion; detection of
antibodies to minor
antigens may also be
affected
false positive test results
for patients with IgGĸ Mprotein which may affect
ability to evaluate
response to treatment
binding of daratumumab to
CD38 on red blood cells.
• type and screen patients
prior to starting
daratumumab
• notify blood bank as
needed for transfusion.
detection of daratumumab
by SPE or IFE assays
• additional tests may be
required to evaluate
response.
Serum protein
electrophoresis (SPE) and
immunofixation (IFE)
3
assays
SUPPLY AND STORAGE:
Injection: Janssen Biotech, Inc (USA). supplies daratumumab as single-dose vials (100mg/5mL and 400mg/20mL)
3,8
at a concentration of 20 mg/mL. Refrigerate. Protect from light. Do not shake.
For basic information on the current brand used at the BC Cancer Agency, see Chemotherapy Preparation
and Stability Chart in Appendix.
SOLUTION PREPARATION AND COMPATIBILITY:
For basic information on the current brand used at the BC Cancer Agency, see Chemotherapy Preparation
and Stability Chart in Appendix.
Additional information:
• administer with a low protein binding in-line filter (0.22 or 0.2 micron)
8
• infusion should be completed within 15 hours
8
• do not mix with or infuse with other medications
8
Compatibility: consult detailed reference
PARENTERAL ADMINISTRATION:
BCCA administration guideline noted in bold, italics
Subcutaneous
no information found
Intramuscular
Direct intravenous
no information found
8
do NOT use
BC Cancer Agency Cancer Drug Manual
Developed: 25 May 2016
Revised: 1 July 2016
©
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Daratumumab interim monograph
Daratumumab (interim monograph)
BCCA administration guideline noted in bold, italics
3
Continuous infusion
over 3.25-15 hours (refer to protocol by which patient is being treated).
In the absence of other guidelines, follow incremental infusion rate as
below:
Dilution
Initial rate
Rate
Maximum
volume
(first hour)
increment
rate
st
1 infusion
1000 mL
50 mL/h
50 mL/h
200 mL/h
every hour
nd
a
2 infusion
500 mL
50 mL/h
50 mL/h
200 mL/h
every hour
500 mL
100 mL/h
50 mL/h
subsequent
200 mL/h
b
infusions
every hour
no information found
Intraperitoneal
Intrapleural
no information found
no information found
Intrathecal
Intra-arterial
no information found
no information found
Intravesical
no information found
Intermittent infusion
a
b
Escalate only if there are no Grade 1 or greater infusion reactions during the first 3 hours of the first infusion
Escalate only if there are no Grade 1 or greater infusion reactions during a final infusion rate of ≥100mL/hr in the first 2 infusions
DOSAGE GUIDELINES:
Refer to protocol by which patient is being treated. Numerous dosing schedules exist and depend on disease,
response and concomitant therapy. Guidelines for dosing also include consideration of absolute neutrophil count
(ANC). Dosage may be delayed or discontinued in patients with bone marrow depression due to cytotoxic/radiation
therapy or with other toxicities.
Adults:
BCCA usual dose noted in bold, italics
Cycle Length:
4 weeks:
2,3
Intravenous:
Cycles 1 and 2:
16 mg/kg IV for one dose on days 1, 8, 15, and 22
Cycles 3 through 6:
16mg/kg IV for one dose on days 1 and 15
Subsequent cycles:
16mg/kg IV for one dose on day 1
3
Dose in renal failure:
no starting dose adjustment necessary
3
• no dose adjustment for mild impairment (total bilirubin 11.5X ULN OR AST > ULN);
• no information found for moderate or severe impairment
Dose in hepatic failure:
BC Cancer Agency Cancer Drug Manual
Developed: 25 May 2016
Revised: 1 July 2016
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Daratumumab (interim monograph)
REFERENCES:
1. Lokhorst HM, Plesner T, Laubach JP, et al. Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma.
N.Engl.J.Med. 2015;373(13):1207-1219.
2. Lonial S, Weiss BM, Usmani SZ, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma
(SIRIUS): an open-label, randomised, phase 2 trial. Lancet 2016.
3. Genentech Inc. DARZALEX® full prescribing information. Horsham, PA, USA; Nov 2015.
4. Laubach JP, Richardson PG. CD38-Targeted Immunochemotherapy in Refractory Multiple Myeloma: A New Horizon.
Clin.Cancer Res. 2015;21(12):2660-2662.
5. van de Donk NW, Moreau P, Plesner T, et al. Clinical efficacy and management of monoclonal antibodies targeting CD38 and
SLAMF7 in multiple myeloma. Blood 2016;127(6):681-695.
6. BC Cancer Agency. (SCNAUSEA) Guidelines for Prevention and Treatment of Chemotherapy-induced Nausea and Vomiting in
Adults. Vancouver, British Columbia: BC Cancer Agency; 1 Mar 2012.
7. BC Cancer Agency Provincial Systemic Therapy Program. Provincial Systemic Therapy Program Policy III-20: Prevention and
Management of Extravasation of Chemotherapy. Vancouver, British Columbia: BC Cancer Agency; 1 November 2014.
8. Lexicomp Online® (database on the Internet). Daratumumab. Lexi-Comp Inc., 17 November 2015. Available at:
http://online.lexi.com. Accessed 15 March 2016.
BC Cancer Agency Cancer Drug Manual
Developed: 25 May 2016
Revised: 1 July 2016
©
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Daratumumab interim monograph