l NATIONAL FUNDING/ACCESS DECISIONS
▶ Bevacizumab and cetuximab for the treatment of metastatic
colorectal cancer (January 2007) NICE TA118
Bevacizumab in combination with fluorouracil plus folinic
acid, with or without irinotecan, is not recommended for
the first-line treatment of metastatic colorectal cancer; see
also NICE guidance Cetuximab, bevacizumab and
panitumumab for the treatment of metastatic colorectal
cancer after first-line chemotherapy.
www.nice.org.uk/guidance/TA118
▶ Bevacizumab in combination with oxaliplatin and either
fluorouracil plus folinic acid or capecitabine for the treatment
of metastatic colorectal cancer (December 2010) NICE TA212
Bevacizumab in combination with oxaliplatin and either
fluorouracil plus folinic acid or capecitabine is not
recommended for the treatment of metastatic colorectal
www.nice.org.uk/guidance/TA212
▶ Cetuximab, bevacizumab and panitumumab for the treatment
of metastatic colorectal cancer after first-line chemotherapy
Bevacizumab in combination with non-oxaliplatin
(fluoropyrimidine-based) chemotherapy is not
recommended for the treatment of patients with
and cetuximab for the treatment of metastatic colorectal
www.nice.org.uk/guidance/TA242
▶ Bevacizumab (first-line), sorafenib (first and second-line),
sunitinib (second-line) and temsirolimus (first-line) for the
treatment of advanced and/or metastatic renal cell carcinoma
Bevacizumab, sorafenib, and temsirolimus are not
recommended as first-line treatments for people with
advanced and/or metastatic renal cell carcinoma.
Sorafenib and sunitinib are not recommended as secondline treatments for people with advanced and/or
metastatic renal cell carcinoma.
www.nice.org.uk/guidance/TA178
▶ Bevacizumab in combination with a taxane for the first-line
treatment of metastatic breast cancer (February 2011)
Bevacizumab in combination with a taxane is not
recommended for the first-line treatment of metastatic
www.nice.org.uk/guidance/TA214
Bevacizumab in combinations with capecitabine is not
recommended within its marketing authorisation for the
first-line treatment of metastatic breast cancer, that is,
when treatment with other chemotherapy options
including taxanes or anthracyclines is not considered
appropriate, or when taxanes or anthracyclines have been
used as part of adjuvant treatment in the previous
www.nice.org.uk/guidance/TA263
▶ Bevacizumab in combination with paclitaxel and carboplatin
for the first-line treatment of advanced ovarian cancer (May
Bevacizumab in combination with paclitaxel and
carboplatin is not recommended for the first-line
treatment of advanced ovarian cancer (including fallopian
tube and primary peritoneal cancer).
www.nice.org.uk/guidance/TA284
▶ Bevacizumab in combination with gemcitabine and
carboplatin for the treatment of the first recurrence of
platinum-sensitive advanced ovarian cancer (May 2013)
Bevacizumab in combination with gemcitabine and
carboplatin is not recommended within its marketing
authorisation, that is, for the treatment of the first
recurrence of platinum-sensitive advanced ovarian cancer
(including fallopian tube and primary peritoneal cancer)
that has not been previously treated with bevacizumab or
other vascular endothelial growth factor (VEGF) inhibitors
or VEGF receptor-targeted agents.
www.nice.org.uk/guidance/TA285
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (May 2012)
that bevacizumab (Avastin ®) is not recommended for use
within NHS Scotland for the first line treatment of patients
with metastatic breast cancer in whom treatment with
other chemotherapy options including taxanes or
anthracyclines is not considered appropriate.
The Scottish Medicines Consortium has advised
(September 2015) that bevacizumab (Avastin ®) is accepted
for restricted use within NHS Scotland in combination
with paclitaxel for the treatment of adult patients with
platinum-resistant recurrent epithelial ovarian, fallopian
tube, or primary peritoneal cancer who received no more
than two prior chemotherapy regimens and who have not
received prior therapy with bevacizumab or other vascular
endothelial growth factor (VEGF) inhibitors or VEGF
The Scottish Medicines Consortium has advised
(November 2015) that bevacizumab (Avastin ®) is accepted
for restricted use within NHS Scotland in combination
with carboplatin and paclitaxel for the first-line treatment
of advanced FIGO stage IV epithelial ovarian, fallopian
tube, or primary peritoneal cancer.
All Wales Medicines Strategy Group (AWMSG) decisions
The All Wales Medicines Strategy Group has advised
(September 2017) that bevacizumab (Avastin ®) is not
recommended for use within NHS Wales in combination
with paclitaxel and cisplatin, or alternatively, paclitaxel
and topotecan in patients who cannot receive platinum
therapy, for the treatment of adults with persistent,
recurrent, or metastatic carcinoma of the cervix. The case
for cost-effectiveness has not been proven.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Avastin (Roche Products Ltd)
Bevacizumab 25 mg per 1 ml Avastin 400mg/16ml solution for
infusion vials | 1 vial P £924.40 (Hospital only)
Avastin 100mg/4ml solution for infusion vials | 1 vial P £242.66
l DRUG ACTION The anti-lymphocyte monoclonal
antibodies cause lysis of B lymphocytes.
Relapsed or refractory Philadelphia chromosomenegative acute lymphoblastic leukaemia (initiated by a
▶ BY CONTINUOUS INTRAVENOUS INFUSION
▶ Adult: (consult product literature)
Philadelphia chromosome-negative acute lymphoblastic
leukaemia in complete remission with minimal residual
disease (initiated by a specialist)
▶ BY CONTINUOUS INTRAVENOUS INFUSION
▶ Adult (body-weight 45 kg and above): (consult product
BNF 78 Antibody responsive malignancy 863
Immune system and malignant disease
l CAUTIONS Aphasia . brain injuries (severe). cerebellar
▶ Pre-medication Manufacturer advises pre-medication with a
corticosteroid and an anti-pyretic—consult product
▶ Neurological events There is potentially a higher risk of
neurological events in patients with clinically relevant
CNS pathology—manufacturer advises caution.
l INTERACTIONS → Appendix 1: monoclonal antibodies
syndrome . vomiting . weight increased
▶ Uncommon Capillary leak syndrome . cranial nerve
reported; manufacturer advises monitor for signs and
symptoms of pancreatitis during treatment—temporary
interruption or discontinuation may be required (consult
Cytokine release syndrome, infusion-reactions and
tumour lysis syndrome Life-threatening (including fatal)
cases of cytokine release syndrome and tumour lysis
syndrome have been reported in patients taking
blinatumomab. Manufacturer advises monitor signs and
symptoms of cytokine release syndrome and infusion
reactions during treatment; temporary interruption or
discontinuation may be required—consult product
l CONCEPTION AND CONTRACEPTION Manufacturer advises
effective contraception during treatment and for at least
48 hours after treatment in women of child-bearing
potential. See also Pregnancy and reproductive function in
l PREGNANCY Manufacturer advises avoid unless potential
benefit outweighs risk—no information available; if
exposed during pregnancy, monitor infant for B-cell
depletion. See also Pregnancy and reproductive function
l BREAST FEEDING Manufacturer advises avoid during and
for at least 48 hours after treatment—no information
l HEPATIC IMPAIRMENT Manufacturer advises caution in
severe impairment (no information available).
l RENAL IMPAIRMENT Manufacturer advises caution in
severe impairment—no information available.
l MONITORING REQUIREMENTS Manufacturer advises
neurological examination prior to the initiation of
treatment and continued monitoring during treatment—
l HANDLING AND STORAGE Manufacturer advises store in a
refrigerator (2–8°C); consult product literature for storage
conditions after reconstitution and dilution.
l PATIENT AND CARER ADVICE A patient alert card should be
provided. Educational materials should be provided to
patients, carers and healthcare professionals to ensure
blinatumomab is used in a safe and effective way, and to
prevent the risk of medication errors and neurological
events—consult product information.
Driving and skilled tasks Manufacturer advises patients and
carers should be counselled about the effects on driving
and performance of skilled tasks—increased risk of
confusion, disorientation, co-ordination and balance
disorders, seizures and disturbances in consciousness.
l NATIONAL FUNDING/ACCESS DECISIONS
Blinatumomab is recommended within its marketing
authorisation as an option for treating Philadelphia
company provides it with the discount agreed in the
www.nice.org.uk/guidance/ta450
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder for solution for infusion
EXCIPIENTS: May contain Polysorbates
Blinatumomab 38.5 microgram Blincyto 38.5micrograms powder
for concentrate and solution for solution for infusion vials |
Brentuximab vedotin 08-May-2019
CD30 positive Hodgkin lymphoma (specialist use only)|
Systemic anaplastic large cell lymphoma (specialist use
only)| CD30 positive cutaneous T-cell lymphoma
▶ Adult: (consult product literature)
l CAUTIONS Elevated BMI—risk of hyperglycaemia . high
tumour burden—risk of tumour lysis syndrome .rapidly
proliferating tumours—risk of tumour lysis syndrome
l INTERACTIONS → Appendix 1: monoclonal antibodies
▶ Uncommon Cytomegalovirus infection reactivation . pancreatitis acute .tumour lysis syndrome
▶ Rare or very rare Severe cutaneous adverse reactions
▶ Frequency not known Acute respiratory distress syndrome
l CONCEPTION AND CONTRACEPTION Effective
contraception required during treatment and for 6 months
after treatment in men and women.
l PREGNANCY Avoid unless potential benefit outweighs risk
l BREAST FEEDING Avoid—no information available.
864 Antibody responsive malignancy BNF 78
Immune system and malignant disease
▶ Monitor for symptoms of progressive multifocal
leucoencephalopathy (presenting as new or worsening
neurological, cognitive or behavioural signs or symptoms).
▶ Monitor for new or worsening abdominal pain—
investigate and withhold treatment if acute pancreatitis
suspected and discontinue if confirmed (fatal cases
▶ Monitor for pulmonary toxicity—treat symptoms
▶ Routinely monitor hepatic function.
▶ Monitor for infusion-related (including anaphylactic)
▶ Monitor for signs of peripheral neuropathy—consult
product literature for treatment adjustment.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Brentuximab vedotin for treating relapsed or refractory
systemic anaplastic large cell lymphoma (October 2017)
Brentuximab vedotin is recommended as an option for
treating relapsed or refractory systemic anaplastic large
cell lymphoma in adults, only if:
. they have an Eastern Cooperative Oncology Group
performance status of 0 or 1, and
. the manufacturer provides brentuximab vedotin
according to the commercial access agreement with NHS
These recommendations are not intended to affect
treatment that was started in the NHS before this guidance
was published. Adults having treatment outside these
recommendations may continue without change to the
funding arrangements in place before this guidance was
published, until they and their NHS clinician consider it
www.nice.org.uk/guidance/ta478
▶ Brentuximab vedotin for treating CD30-positive Hodgkin
lymphoma (June 2018) NICE TA524
Brentuximab vedotin is recommended as an option for
treating CD30-positive Hodgkin lymphoma in adults with
relapsed or refractory disease, only if:
. they have already had autologous stem cell transplant,
. they have already had at least 2 previous therapies when
autologous stem cell transplant or multi-agent
chemotherapy are not suitable, and
. the manufacturer provides brentuximab vedotin
according to the commercial arrangement.
Patients whose treatment was started within the NHS
before this guidance was published should have the option
to continue treatment, without change to their funding
arrangements, until they and their NHS clinician consider
www.nice.org.uk/guidance/ta524
▶ Brentuximab vedotin for treating CD30-positive cutaneous Tcell lymphoma (April 2019) NICE TA577
Brentuximab vedotin (Adcetris ®) is recommended as an
option for treating CD30-positive cutaneous T-cell
lymphoma (CTCL) after at least one systemic therapy in
. they have mycosis fungoides stage IIB or over, primary
cutaneous anaplastic large cell lymphoma or Sézary
. the manufacturer provides brentuximab vedotin
according to the commercial arrangement.
Patients whose treatment was started within the NHS
before this guidance was published should have the option
to continue treatment, without change to their funding
arrangements, until they and their NHS clinician consider
www.nice.org.uk/guidance/ta577
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder for solution for infusion
EXCIPIENTS: May contain Polysorbates
ELECTROLYTES: May contain Sodium
Brentuximab vedotin 50 mg Adcetris 50mg powder for concentrate
for solution for infusion vials | 1 vial P £2,500.00
Treatment of wild-type RAS metastatic colorectal cancer
in patients with tumours expressing epidermal growth
factor receptor, as combination therapy, or as
monotherapy if oxaliplatin- and irinotecan-based
therapy has failed or if irinotecan is not tolerated |
Treatment of locally advanced squamous cell cancer of
the head and neck (in combination with radiotherapy)|
Treatment of recurrent or metastatic squamous cell
cancer of the head and neck (in combination with
▶ Adult (initiated by a specialist): (consult product
literature or local protocols)
MHRA/CHM ADVICE: EPIDERMAL GROWTH FACTOR RECEPTOR
(EGFR) INHIBITORS: SERIOUS CASES OF KERATITIS AND
ULCERATIVE KERATITIS (MAY 2012)
Keratitis and ulcerative keratitis have been reported
following treatment with epidermal growth factor
receptor (EGFR) inhibitors for cancer (cetuximab,
erlotinib, gefitinib and panitumumab). In rare cases, this
has resulted in corneal perforation and blindness.
Patients undergoing treatment with EGFR inhibitors
who present with acute or worsening signs and
symptoms suggestive of keratitis should be referred
promptly to an ophthalmology specialist. Treatment
should be interrupted or discontinued if ulcerative
Patients must receive an antihistamine and a
corticosteroid at least one hour before infusion.
Resuscitation facilities should be available and
treatment should be initiated by a specialist.
l CONTRA-INDICATIONS Combination of cetuximab with
oxaliplatin-containing chemotherapy is contra-indicated
in patients with metastatic colorectal cancer who have
mutant or unknown RAS status . RAS mutated colorectal
tumours (or if RAS tumour status unknown)
l CAUTIONS Cardiopulmonary disease . cardiovascular
disease . history of keratitis . pulmonary disease—
discontinue if interstitial lung disease .risk factors for
keratitis . severe dry eye . ulcerative keratitis (including
l INTERACTIONS → Appendix 1: monoclonal antibodies
▶ Common or very common Appetite decreased . cytokine
release syndrome . dehydration . diarrhoea . electrolyte
imbalance . eye inflammation . fatigue . headache . infusion
related reaction . mucositis . nausea . skin eruption . vomiting
▶ Uncommon Embolism and thrombosis . interstitial lung
▶ Rare or very rare Severe cutaneous adverse reactions
▶ Frequency not known Meningitis aseptic . superinfection of
BNF 78 Antibody responsive malignancy 865
Immune system and malignant disease
l CONCEPTION AND CONTRACEPTION Contraceptive advice
required, see Pregnancy and reproductive function in
l PREGNANCY Use only if potential benefit outweighs risk—
no information available. See also Pregnancy and
reproductive function in Cytotoxic drugs p. 888.
l BREAST FEEDING Avoid breast-feeding during and for
2 months after treatment—no information available.
l PRE-TREATMENT SCREENING Evidence of non-mutated
(wild-type) RAS status (at exons 2, 3 and 4 of KRAS and
NRAS) is required before cetuximab is initiated for the
treatment of metastatic colorectal cancer, and should be
determined by an experienced laboratory using a validated
l DIRECTIONS FOR ADMINISTRATION Resuscitation facilities
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Cetuximab for the treatment of locally advanced squamous
cell cancer of the head and neck (June 2008) NICE TA145
Cetuximab in combination with radiotherapy is an option
for the treatment of locally advanced squamous cell cancer
of the head and neck in patients who have a Karnofsky
performance status of 90% or greater and when all forms
of platinum-based chemoradiotherapy treatment are
www.nice.org.uk/guidance/TA145
▶ Cetuximab, bevacizumab and panitumumab for the treatment
of metastatic colorectal cancer after first-line chemotherapy
Cetuximab monotherapy or combination chemotherapy is
not recommended for the treatment of patients with
metastatic colorectal cancer that has progressed after firstline chemotherapy.
www.nice.org.uk/guidance/TA242
▶ Cetuximab and panitumumab for previously untreated
metastatic colorectal cancer (updated September 2017)
Cetuximab is recommended, within its marketing
authorisation, as an option for previously untreated
. 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX), or
. 5-fluorouracil, folinic acid and irinotecan (FOLFIRI).
This advice is contingent upon the manufacturer providing
cetuximab with the discount agreed in the commercial
www.nice.org.uk/guidance/TA439
▶ Cetuximab for treating recurrent or metastatic squamous cell
cancer of the head and neck (August 2017) NICE TA473
Cetuximab in combination with platinum-based
chemotherapy is recommended as an option for treating
recurrent or metastatic squamous cell cancer of the head
. if the cancer started in the oral cavity, and
. when the company provides the drug in line with the
commercial access agreement with NHS England.
Patients currently receiving cetuximab whose disease does
not meet the above criteria may continue treatment until
they and their clinician consider it appropriate to stop.
www.nice.org.uk/guidance/TA473
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Cetuximab 5 mg per 1 ml Erbitux 100mg/20ml solution for infusion
vials | 1 vial P £178.10 (Hospital only)
Erbitux 500mg/100ml solution for infusion vials | 1 vial P £890.50 (Hospital only)
l DRUG ACTION Daratumumab is a monoclonal antibody
that binds to CD38, a cell-surface protein, resulting in
tumour cell death by immune-mediated actions and
Multiple myeloma (as monotherapy after failure of a
proteasome inhibitor and an immunomodulatory agent)
(specialist use only)| Multiple myeloma (in combination
with lenalidomide and dexamethasone in patients who
have received at least one prior therapy) (specialist use
▶ Adult: 16 mg/kg once weekly for weeks 1 to 8, for week
1, dose can alternatively be divided over 2 consecutive
days, then 16 mg/kg every 2 weeks for weeks 9 to 24,
then 16 mg/kg every 4 weeks for week 25 onwards until
disease progression, for dose interruption or infusion
rate reduction due to infusion-related reactions or
side-effects—consult product literature
Multiple myeloma (in combination with bortezomib and
dexamethasone in patients who have received at least
one prior therapy) (specialist use only)
▶ Adult: 16 mg/kg once weekly for weeks 1 to 9, for week
1, dose can alternatively be divided over 2 consecutive
days, then 16 mg/kg every 3 weeks for weeks 10 to 24,
then 16 mg/kg every 4 weeks for week 25 onwards until
disease progression, for dose interruption or infusion
rate reduction due to infusion-related reactions or
side-effects—consult product literature
Newly diagnosed multiple myeloma (in combination with
bortezomib, melphalan and prednisone) (specialist use
▶ Adult: 16 mg/kg once weekly for weeks 1 to 6, for week
1, dose can alternatively be divided over 2 consecutive
days, then 16 mg/kg every 3 weeks for weeks 7 to 54,
then 16 mg/kg every 4 weeks for week 55 onwards until
disease progression, for dose interruption or infusion
rate reduction due to infusion-related reactions or
side-effects—consult product literature
l CAUTIONS History of obstructive pulmonary disorder
(consider additional post-medication—consult product
literature). patients may need pre-medication to minimise
adverse reactions .risk of herpes zoster reactivation
(consider antiviral prophylaxis)
▶ Infusion-related reactions Serious infusion-related reactions
can occur and daratumumab should only be administered
when appropriately trained staff and resuscitation
facilities are immediately available; manufacturer advises
pre-medication with a corticosteroid, an antihistamine
and an anti-pyretic and post-medication with oral
corticosteroids—consult product literature. Manufacturer
advises patients should be closely monitored for signs of
infusion-related reactions during and after administration;
in the event of a hypersensitivity reaction, treatment
should be stopped immediately and appropriate
l INTERACTIONS → Appendix 1: monoclonal antibodies
infection . infusion related reaction . lymphopenia . muscle
866 Antibody responsive malignancy BNF 78
Immune system and malignant disease
oedema .respiratory disorders .throat irritation . thrombocytopenia . vomiting
▶ Frequency not known Allergic rhinitis . chest discomfort. hypotension . pruritus
SIDE-EFFECTS, FURTHER INFORMATION Manufacturer
advises treatment should be immediately interrupted if an
infusion-related reaction of any grade or severity occurs—
consult product literature for specific management
l CONCEPTION AND CONTRACEPTION Manufacturer advises
effective contraception in women of childbearing potential
during treatment and for 3 months after stopping
treatment. See also Pregnancy and reproductive function in
l PREGNANCY Manufacturer advises avoid unless potential
benefit outweighs risk—no information available. See also
Pregnancy and reproductive function in Cytotoxic drugs
l BREAST FEEDING Manufacturer advises avoid—no
l EFFECT ON LABORATORY TESTS Possible positive indirect
Coombs test (may affect antibody screening).
l HANDLING AND STORAGE Manufacturer advises store in a
refrigerator at 2–8°C; consult product literature for
storage advice following dilution.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Daratumumab monotherapy for treating relapsed and
refractory multiple myeloma (March 2018) NICE TA510
Daratumumab monotherapy is recommended for use
within the Cancer Drugs Fund as an option for treating
relapsed and refractory multiple myeloma in adults whose
previous therapy included a proteasome inhibitor and an
immunomodulator, and whose disease progressed on the
. they have daratumumab after 3 previous therapies, and
. the conditions in the managed access agreement are
Patients whose treatment was started within the NHS
before this guidance was published should have the option
to continue treatment, without change to their funding
arrangements, until they and their NHS clinician consider
www.nice.org.uk/guidance/ta510
▶ Daratumumab with bortezomib and dexamethasone for
previously treated multiple myeloma (April 2019) NICE TA573
Daratumumab (Darzalex ®) plus bortezomib plus
dexamethasone is recommended for use within the Cancer
Drugs Fund as an option for treating relapsed multiple
myeloma in people who have had one previous treatment.
It is recommended only if the conditions in the managed
access agreement for daratumumab plus bortezomib plus
Patients whose treatment was started within the NHS
before this guidance was published should have the option
to continue treatment, without change to their funding
arrangements, until they and their NHS clinician consider
www.nice.org.uk/guidance/ta573
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (October
2017) that daratumumab (Darzalex ®) is accepted for
restricted use within NHS Scotland as monotherapy for use
as a fourth-line treatment option for adults with relapsed
and refractory multiple myeloma, only if a proteasome
inhibitor and an immunomodulatory agent have been used
as prior therapy and disease demonstrated progression on
the last therapy. This advice is contingent upon the
continuing availability of the patient access scheme in
NHS Scotland or a list price that is equivalent or lower.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
EXCIPIENTS: May contain Polysorbates
ELECTROLYTES: May contain Sodium
▶ Darzalex (Janssen-Cilag Ltd) A
Daratumumab 20 mg per 1 ml Darzalex 400mg/20ml concentrate
for solution for infusion vials | 1 vial P £1,440.00
Darzalex 100mg/5ml concentrate for solution for infusion vials | 1 vial P £360.00
l DRUG ACTION Dinutuximab beta is a chimeric monoclonal
antibody; it specifically targets the carbohydrate moiety of
disialoganglioside 2, which is overexpressed on
High-risk neuroblastoma (specialist use only)
▶ Adult: (consult product literature)
l CONTRA-INDICATIONS Acute grade 3 or 4, or extensive
chronic graft-versus-host disease
l CAUTIONS Avoid vaccinations during and for at least
10 weeks after treatment cessation (increased risk of
immune stimulation and neurological toxicity). ensure
absence of systemic infection—any other infection should
be controlled before treatment initiation . pre-medication
must be administered to minimise the risk of infusionrelated reactions and neuropathic pain
▶ Pre-medication Severe infusion-related reactions can occur
and dinutuximab beta should only be administered when
appropriately trained staff and resuscitation facilities are
particularly during the first and second treatment course;
discontinue immediately if reaction occurs and treat as
indicated—consult product literature.
Manufacturer advises pre-medication with non-opioid
analgesics, gabapentin and opioids—consult product
l INTERACTIONS → Appendix 1: monoclonal antibodies
inflammation . fever. fluid imbalance . gastrointestinal
abnormalities . vision disorders . vomiting . weight changes
disease . posterior reversible encephalopathy syndrome
l CONCEPTION AND CONTRACEPTION Manufacturer advises
women of childbearing potential should use contraception
during and for 6 months after stopping treatment. See also
BNF 78 Antibody responsive malignancy 867
Immune system and malignant disease
Pregnancy and reproductive function in Cytotoxic drugs
l PREGNANCY Manufacturer advises avoid—no information
available. See also Pregnancy and reproductive function in
l BREAST FEEDING Manufacturer advises avoid during
treatment and for 6 months after the last dose—no
▶ Manufacturer advises pre-treatment evaluation of pulse
oximetry, bone marrow function, liver function and renal
function—consult product literature for values required for
▶ Manufacturer advises monitor circulatory and respiratory
function—risk of capillary leak syndrome.
▶ Manufacturer advises monitor liver function and
l HANDLING AND STORAGE Manufacturer advises store in a
refrigerator (2–8°C)—consult product literature for further
information regarding storage conditions outside
refrigerator and after preparation of the infusion.
Driving and skilled tasks Manufacturer advises patients
should not use or drive machines during treatment.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Dinutuximab beta for treating neuroblastoma (August 2018)
Dinutuximab beta (Qarziba ®) is recommended as an
option for treating high-risk neuroblastoma in people aged
12 months and over whose disease has at least partially
responded to induction chemotherapy, followed by
myeloablative therapy and stem cell transplant, only if:
. they have not already had anti-GD2 immunotherapy,
. the manufacturer provides dinutuximab beta according
to the commercial arrangement.
Patients whose treatment was started within the NHS
before this guidance was published should have the option
to continue treatment, without change to their funding
arrangements, until they and their NHS clinician consider
www.nice.org.uk/guidance/ta538
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (November
2018) that dinutuximab beta (Qarziba ®) is accepted for use
within NHS Scotland for the treatment of high-risk
neuroblastoma in patients aged 12 months and over whose
disease has at least partially responded to induction
chemotherapy, followed by myeloablative therapy and
stem cell transplantation, as well as patients with a history
of relapsed or refractory neuroblastoma, with or without
In patients with a history of relapsed or refractory
disease and in patients who have not achieved a complete
response after first line therapy, dinutuximab beta should
be combined with interleukin-2.
This advice is contingent upon the continuing
availability of the patient access scheme in NHS Scotland
or a list price that is equivalent or lower.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Dinutuximab beta 4.5 mg per 1 ml Qarziba 20mg/4.5ml
concentrate for solution for infusion vials | 1 vial P £7,610.00
l DRUG ACTION Durvalumab is a human monoclonal
antibody that selectively binds to programmed cell death
ligand-1 (PD-L1), blocking its interaction with the
programmed death-1 (PD-1) receptor and with CD80, and
thereby potentiating an immune response to tumour cells.
Non-small cell lung cancer (initiated by a specialist)
▶ Adult: 10 mg/kg every 2 weeks, consult product
literature for information on dose adjustments based
on individual patient safety and tolerability
l INTERACTIONS → Appendix 1: monoclonal antibodies
related reaction . myalgia . night sweats . peripheral
oedema .respiratory disorders . skin reactions .thyroiditis
▶ Rare or very rare Diabetes insipidus . hypophysitis . hypopituitarism . myocarditis
SIDE-EFFECTS, FURTHER INFORMATION Immune-related
reactions Manufacturer advises that most immunerelated adverse reactions resolved with appropriate
management, including initiation of immunosuppressive
treatment and treatment modifications—consult product
Infusion-related reactions Manufacturer advises to
permanently discontinue treatment in patients with severe
l CONCEPTION AND CONTRACEPTION Manufacturer advises
effective contraception in women of childbearing potential
during treatment and for at least 3 months after stopping
treatment. See also Pregnancy and reproductive function in
l PREGNANCY Manufacturer advises avoid—no information
available. See also Pregnancy and reproductive function in
l BREAST FEEDING Manufacturer advises avoid—no
l MONITORING REQUIREMENTS Manufacturer advises
monitor for signs and symptoms of infusion- and immunerelated reactions—consult product literature.
l DIRECTIONS FOR ADMINISTRATION Manufacturer advises
for intravenous infusion, dilute to a concentration between
1 mg/mL and 15 mg/mL with Glucose 5% or Sodium
Chloride 0.9%; give over 60 minutes through a low-protein
binding in-line filter (pore size 0.2 or 0.22 micron).
l HANDLING AND STORAGE Manufacturer advises store in a
refrigerator (2–8°C) and protect from light—consult
product literature for storage conditions after preparation
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
EXCIPIENTS: May contain Polysorbates
▶ Imfinzi (AstraZeneca UK Ltd) A
Durvalumab 50 mg per 1 ml Imfinzi 120mg/2.4ml concentrate for
solution for infusion vials | 1 vial P £592.00
Imfinzi 500mg/10ml concentrate for solution for infusion vials | 1 vial P £2,466.00
868 Antibody responsive malignancy BNF 78
Immune system and malignant disease
l DRUG ACTION Elotuzumab is a monoclonal antibody that
targets the signalling lymphocytic activation molecule
family member 7 (SLAMF7) protein, thereby activating
natural killer cells and mediating myeloma cell death.
Multiple myeloma in patients who have received at least
one prior therapy (in combination with lenalidomide and
dexamethasone) (specialist use only)
▶ Adult: 10 mg/kg every week, on days 1, 8, 15 and 22 of
cycles 1 and 2, then 10 mg/kg every 2 weeks, on days 1
l CAUTIONS Pre-medication must be administered to
minimise the development of infusion-related reactions—
consult product literature . secondary primary
▶ Secondary primary malignancies Manufacturer advises to
monitor for the development of secondary primary
malignancy before and during treatment with elotuzumab.
l INTERACTIONS → Appendix 1: monoclonal antibodies
▶ Common or very common Chest pain . cough . deep vein
related reaction . lymphopenia . mood altered . night
sweats . numbness . oropharyngeal pain . weight decreased
SIDE-EFFECTS, FURTHER INFORMATION Side-effects
reported when used in combination with lenalidomide and
dexamethasone or bortezomib and dexamethamsone.
Infusion-related reactions Manufacturer advises for
mild-to-moderate infusion reactions interrupt treatment
or reduce infusion rate, and monitor closely (consult
product literature); permanently discontinue therapy in
l CONCEPTION AND CONTRACEPTION Manufacturer advises
effective contraception in men and women of childbearing
potential; male patients should continue effective
contraceptive measures for 180 days after stopping
treatment if their partner is pregnant or of childbearing
potential. See also Pregnancy and reproductive function in
l PREGNANCY Manufacturer advises avoid unless
essential—no information available. See also Pregnancy
and reproductive function in Cytotoxic drugs p. 888.
l HANDLING AND STORAGE Manufacturer advises store in a
refrigerator (2–8°C); consult product literature for storage
conditions after preparation of the infusion.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder for solution for infusion
EXCIPIENTS: May contain Polysorbates, sucrose
▶ Empliciti (Bristol-Myers Squibb Pharmaceuticals Ltd) A
Elotuzumab 300 mg Empliciti 300mg powder for concentrate for
solution for infusion vials | 1 vial P £1,085.00
Elotuzumab 400 mg Empliciti 400mg powder for concentrate for
solution for infusion vials | 1 vial P £1,446.00
Gemtuzumab ozogamicin 17-Oct-2018
l DRUG ACTION Gemtuzumab ozogamicin is a monoclonal
antibody that binds to CD33-expressing tumour cells to
induce cell cycle arrest and apoptotic cell death.
CD33-positive acute myeloid leukaemia (specialist use
▶ Adult: (consult product literature)
l CAUTIONS Adverse-risk cytogenetics (consider benefits
hepatotoxicity). pre-medication recommended to
▶ Pre-medication Serious infusion-related reactions can occur
and gemtuzumab ozogamicin should only be administered
when appropriately trained staff and resuscitation
facilities are immediately available; manufacturer advises
pre-medication with a corticosteroid, paracetamol and
antihistamine 1 hour prior to dosing, and to take
appropriate measures to help prevent the development of
tumour lysis-related hyperuricaemia—consult product
▶ Frequency not known Interstitial pneumonia
SIDE-EFFECTS, FURTHER INFORMATION Infusion-related
reactions (including fatal cases) can occur during the first
24 hours after administration. Manufacturer advises
interrupt treatment immediately and treat as clinically
indicated (consult product literature); permanent
discontinuation should be strongly considered in patients
who develop signs and symptoms of anaphylaxis.
l CONCEPTION AND CONTRACEPTION Manufacturer advises
women of childbearing potential should use 2 methods of
effective contraception during treatment and for at least
7 months after the last dose; male patients should use 2
methods of effective contraception during treatment and
for at least 4 months after the last dose if their partner is of
childbearing potential. See also Pregnancy and
reproductive function in Cytotoxic drugs p. 888.
l PREGNANCY Manufacturer advises avoid unless potential
benefit outweighs risk—toxicity in animal studies. See also
Pregnancy and reproductive function in Cytotoxic drugs
l BREAST FEEDING Manufacturer advises avoid during
treatment and for at least one month after the last dose—
l HEPATIC IMPAIRMENT Manufacturer advises caution in
moderate-to-severe impairment—increased risk of
developing hepatotoxicity; postpone treatment if serum
transaminases (ALT or AST) greater than 2.5 times the
upper limit of normal or total bilirubin greater than
2 times the upper limit of normal.
▶ Manufacturer advises monitor complete blood counts prior
to each dose as well as signs and symptoms of infection,
BNF 78 Antibody responsive malignancy 869
Comments
Post a Comment
اكتب تعليق حول الموضوع