bleeding and other effects of myelosuppression during
treatment; dose interruption or discontinuation of
treatment may be required—consult product literature.
▶ Manufacturer advises monitor for signs and symptoms of
infusion-related reactions—close clinical monitoring,
including pulse, blood pressure and temperature, should
be performed during infusion; monitor for signs and
symptoms of tumour lysis syndrome.
▶ Manufacturer advises monitor for signs and symptoms of
hepatotoxicity (including hepatic veno-occlusive disease);
liver tests should be monitored prior to each dose—consult
l PRESCRIBING AND DISPENSING INFORMATION
Gemtuzumab ozogamicin is a biological medicine.
Biological medicines must be prescribed and dispensed by
brand name, see Biological medicines and Biosimilar
medicines, under Guidance on prescribing p. 1.
l HANDLING AND STORAGE Manufacturer advises store in a
refrigerator (2–8°C) and protect from light—consult
product literature for storage conditions after
Driving and skilled tasks Manufacturer advises patients and
carers should be counselled on the effects on driving and
performance of skilled tasks—increased risk of fatigue and
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Gemtuzumab ozogamicin for untreated acute myeloid
leukaemia (November 2018) NICE TA545
Gemtuzumab ozogamicin (Mylotarg ®), with daunorubicin
and cytarabine, is recommended as an option for
untreated de novo CD33-positive acute myeloid leukaemia
(AML), except acute promyelocytic leukaemia, in people
. they start induction therapy when either the cytogenetic
test confirms that the disease has favourable,
intermediate or unknown cytogenetics (that is, because
the test was unsuccessful) or when their cytogenetic test
results are not yet available, and
. they start consolidation therapy when their cytogenetic
test confirms that the disease has favourable,
intermediate or unknown cytogenetics (because the test
. the manufacturer provides gemtuzumab ozogamicin
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/ta545
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (October
2018) that gemtuzumab ozogamicin (Mylotarg ®) is
accepted for restricted use within NHS Scotland as
combination therapy with daunorubicin and cytarabine for
the treatment of previously untreated, de novo
CD33-positive acute myeloid leukaemia in patients aged
15 years and above with a favourable, intermediate or
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder for solution for infusion
Gemtuzumab ozogamicin 5 mg Mylotarg 5mg powder for
concentrate for solution for infusion vials | 1 vial P £6,300.00
Inotuzumab ozogamicin 06-Jul-2018
l DRUG ACTION Inotuzumab ozogamicin is a monoclonal
antibody that binds to CD22-expressing tumour cells to
induce cell cycle arrest and apoptotic cell death.
Monotherapy for relapsed or refractory CD22-positive B
cell precursor acute lymphoblastic leukaemia (under
▶ Adult: (consult product literature)
l CONTRA-INDICATIONS Prior confirmed severe or ongoing
sinusoidal obstruction syndrome
l CAUTIONS History of, or predisposition to QT-interval
prolongation (e.g. electrolyte disturbances, concomitant
use of drugs that prolong the QT interval). patients may
need pre-medication to minimise adverse reactions . patients undergoing haematopoietic stem cell
transplantation (increased risk of hepatotoxicity)
▶ Pre-medication Manufacturer advises pre-medication with a
corticosteroid, antipyretic and antihistamine prior to
dosing in all patients and pre-medication to reduce uric
acid levels and hydration in patients with a high tumour
burden (increased risk of tumour lysis syndrome)—consult
l INTERACTIONS → Appendix 1: monoclonal antibodies
syndrome . stomatitis .thrombocytopenia .tumour lysis
SIDE-EFFECTS, FURTHER INFORMATION Manufacturer
advises interrupt treatment if an infusion related reaction
occurs; depending on the severity, discontinuation of the
infusion or administration of steroids and antihistamines
should be considered (consult product literature);
permanently discontinue treatment in severe or lifethreatening infusion reactions.
l CONCEPTION AND CONTRACEPTION Manufacturer advises
effective contraception in women of childbearing potential
during treatment and for at least 8 months after the last
dose; male patients should use effective contraception
during treatment and for at least 5 months after the last
dose if their partner is of childbearing potential. See also
Pregnancy and reproductive function in Cytotoxic drugs
l PREGNANCY Manufacturer advises avoid unless potential
benefit outweighs risk—toxicity in animal studies.
l BREAST FEEDING Manufacturer advises avoid during
treatment and for at least two months after the last dose—
l HEPATIC IMPAIRMENT Manufacturer advises caution if
bilirubin and transaminase levels are raised (limited
information available); avoid in serious ongoing
Dose adjustments Manufacturer advises dose interruption
or discontinuation according to bilirubin and
l PRE-TREATMENT SCREENING Manufacturer advises
baseline CD22 positivity of greater than 0% is required
prior to initiating treatment.
870 Antibody responsive malignancy BNF 78
Immune system and malignant disease
▶ Manufacturer advises monitor complete blood counts prior
to each dose as well as signs and symptoms of infection,
bleeding and other effects of myelosuppresion during
treatment; dose reduction or interruption or
discontinuation of treatment may be required—consult
▶ Manufacturer advises monitor for signs of infusion
related-reactions during and for at least 1 hour after
infusion; monitor for signs and symptoms of tumour lysis
▶ Manufacturer advises ECG and electrolytes should be
monitored prior to the start of treatment and periodically
during treatment; monitor for increases in serum amylase
▶ Manufacturer advises monitor for signs and symptoms of
sinusoidal obstruction syndrome; liver tests should be
monitored prior to and following each dose—consult
l DIRECTIONS FOR ADMINISTRATION Manufacturer advises
resuscitation facilities should be available during
l PRESCRIBING AND DISPENSING INFORMATION Inotuzumab
ozogamicin is a biological medicine. Biological medicines
must be prescribed and dispensed by brand name, see
Biological medicines and Biosimilar medicines, under
Guidance on prescribing p. 1; manufacturer advises to
record the brand name and batch number after each
l HANDLING AND STORAGE Manufacturer advises store in a
refrigerator (2–8°C) and protect from light—consult
product literature for storage conditions after
Driving and skilled tasks Manufacturer advises patients and
carers should be counselled on the effects on driving and
performance of skilled tasks—increased risk of fatigue.
l NATIONAL FUNDING/ACCESS DECISIONS
Inotuzumab ozogamicin (Besponsa ®) is recommended,
within its marketing authorisation, as an option for
treating relapsed or refractory CD22-positive B-cell
precursor acute lymphoblastic leukaemia in adults. People
Inotuzumab ozogamicin is recommended only if the
manufacturer provides it according to the commercial
www.nice.org.uk/guidance/ta541
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (June 2018)
that inotuzumab ozogamicin (Besponsa ®) is accepted for
restricted use within NHS Scotland as monotherapy for the
treatment of adults with relapsed or refractory
CD22-positive B cell precursor acute lymphoblastic
leukaemia (ALL) for whom the intent is to proceed to stem
cell transplantation. Adults with Philadelphia
chromosome positive relapsed or refractory B cell
precursor ALL should have failed treatment with at least
one tyrosine kinase inhibitor. This advice is contingent
upon the continuing availability of the patient access
scheme in NHS Scotland or a list price that is equivalent or
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder for solution for infusion
ELECTROLYTES: May contain Sodium
Inotuzumab ozogamicin 1 mg Besponsa 1mg powder for
concentrate for solution for infusion vials | 1 vial P £8,048.00
l DRUG ACTION Ipilimumab is a monoclonal antibody which
causes T-cell activation resulting in tumour cell death.
Melanoma (as monotherapy) (specialist use only)
▶ Adult: 3 mg/kg every 3 weeks for 4 doses, for dose
interruption or discontinuation of treatment due to
immune-related side-effects—consult product
Melanoma (in combination with nivolumab) (specialist
use only)| Advanced renal cell carcinoma (in
combination with nivolumab) (specialist use only)
▶ Adult: (consult product literature)
MHRA/CHM ADVICE: IPILIMUMAB (YERVOY ®): REPORTS OF
CYTOMEGALOVIRUS (CMV) GASTROINTESTINAL INFECTION OR
There have been post-marketing cases of
gastrointestinal CMV infection or reactivation in
ipilimumab-treated patients reported to have
corticosteroid-refractory immune-related colitis,
Patients should be advised to contact their healthcare
professional immediately at the onset of symptoms of
colitis. Possible causes, including infections, should be
investigated; a stool infection work-up should be
performed and patients screened for CMV. For patients
with corticosteroid-refractory immune-related colitis,
use of an additional immunosuppressive agent should
only be considered if other causes are excluded using
viral PCR on biopsy, and eliminating other viral,
bacterial, and parasitic causes.
l CAUTIONS For full details consult product literature.
l INTERACTIONS → Appendix 1: monoclonal antibodies
▶ Common or very common Alopecia . anaemia . appetite
▶ Uncommon Adrenal hypofunction . alkalosis . allergic
rhinitis . amenorrhoea . arrhythmias . arthritis . brain
oedema . depression . dysarthria . eosinophilia . eye
organ failure . muscle weakness . myopathy . nephritis
autoimmune . neutropenia . pancreatitis . paraneoplastic
BNF 78 Antibody responsive malignancy 871
Immune system and malignant disease
▶ Rare or very rare Myasthenia gravis . proteinuria . thyroiditis
▶ Frequency not known Cytomegalovirus infection
SIDE-EFFECTS, FURTHER INFORMATION A corticosteroid
can be used after starting ipilimumab, to treat immunerelated reactions.
l CONCEPTION AND CONTRACEPTION Use effective
l PREGNANCY Manufacturer advises avoid unless potential
benefit outweighs risk—toxicity in animal studies.
l BREAST FEEDING Manufacturer advises avoid—present in
l HEPATIC IMPAIRMENT Manufacturer advises caution if
bilirubin greater than 3 times upper limit of normal range
or if transaminases equal to or greater than 5 times upper
limit of normal range (limited information available).
▶ Manufacturer advises monitor liver function tests and
thyroid function prior to initiation of treatment and before
▶ Manufacturer advises monitor for signs or symptoms of
immune-related side-effects and gastrointestinal
perforation—consult product literature.
l DIRECTIONS FOR ADMINISTRATION Manufacturer advises
for intravenous infusion, give undiluted or dilute to a
concentration of 1–4 mg/mL with Glucose 5% or Sodium
Chloride 0.9%; give over 90 minutes.
with paracetamol and an antihistamine is recommended.
l HANDLING AND STORAGE Manufacturer advises store in a
refrigerator (2–8 °C) and protect from light—consult
product literature for further information regarding
storage conditions outside refrigerator and after
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Ipilimumab for previously treated advanced (unresectable or
metastatic) melanoma (December 2012) NICE TA268
Ipilimumab (Yervoy ®) is recommended as an option for the
treatment of advanced (unresectable or metastatic)
melanoma in adults who have received prior therapy, only
if the manufacturer provides ipilimumab with the discount
agreed in the patient access scheme.
www.nice.org.uk/guidance/ta268
▶ Ipilimumab for previously untreated advanced (unresectable
or metastatic) melanoma (July 2014) NICE TA319
Ipilimumab (Yervoy ®) is recommended, within its
marketing authorisation, as an option for treating adults
with previously untreated advanced (unresectable or
metastatic) melanoma, only if the manufacturer provides
ipilimumab with the discount agreed in the patient access
www.nice.org.uk/guidance/ta319
▶ Nivolumab in combination with ipilimumab for treating
advanced melanoma (July 2016) NICE TA400
Nivolumab (Opdivo ®) in combination with ipilimumab
(Yervoy ®) is recommended, within its marketing
authorisation, as a treatment option for advanced
(unresectable or metastatic) melanoma in adults, only if
the manufacturer provides ipilimumab with the discount
agreed in the patient access scheme.
www.nice.org.uk/guidance/ta400
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (April 2013)
that ipilimumab (Yervoy ®) is accepted for use within NHS
Scotland for the treatment of advanced (unresectable or
metastatic) melanoma in adults who have received prior
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.
The Scottish Medicines Consortium has advised
(November 2014) that ipilimumab (Yervoy ®) is accepted for
use within NHS Scotland for the first-line treatment of
advanced (unresectable or metastatic) melanoma in
adults. 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.
ELECTROLYTES: May contain Sodium
▶ Yervoy (Bristol-Myers Squibb Pharmaceuticals Ltd)
Ipilimumab 5 mg per 1 ml Yervoy 50mg/10ml concentrate for
solution for infusion vials | 1 vial P £3,750.00 (Hospital only)
Yervoy 200mg/40ml concentrate for solution for infusion vials | 1 vial P £15,000.00 (Hospital only)
l DRUG ACTION Necitumumab is a monoclonal antibody
that binds to the epidermal growth factor receptor (EGFR).
Locally advanced or metastatic epidermal growth factor
receptor expressing squamous non-small-cell lung
cancer, in patients who have not received previous
chemotherapy (in combination with gemcitabine and
cisplatin) (specialist use only)
▶ Adult: 800 mg once daily on days 1 and 8 of a 3-week
cycle, for up to 6 cycles, patients whose disease has not
progressed after combination therapy may continue
with necitumumab monotherapy, for dose adjustments
due to infusion-related reactions or skin reactions—
l CAUTIONS Cardiorespiratory disorders (no information
available). history of thromboembolic events . patients
may need pre-medication to minimise the development of
infusion-related and skin reactions (consult product
literature).risk factors for thromboembolic events
▶ Thromboembolic events Manufacturer advises that
necitumumab should not be administered to patients with
multiple risk factors for thromboembolic events unless the
benefits outweigh the risks. Thromboprophylaxis should
be considered after assessment of a patient’s risk factors.
l INTERACTIONS → Appendix 1: monoclonal antibodies
altered . vomiting . weight decreased
▶ Frequency not known Cardiac arrest. eyelash trichomegaly
872 Antibody responsive malignancy BNF 78
Immune system and malignant disease
l CONCEPTION AND CONTRACEPTION Manufacturer advises
women of child-bearing potential should use effective
contraception during and for 3 months after treatment.
l PREGNANCY Manufacturer advises avoid unless potential
benefit outweighs risk—limited information available. See
also Pregnancy and reproductive function in Cytotoxic drugs
l BREAST FEEDING Manufacturer advises avoid during
treatment and for at least 4 months after the last dose—no
l MONITORING REQUIREMENTS Manufacturer advises
monitor patients during and following each infusion for
signs of hypersensitivity and infusion-related reactions;
monitor electrolytes (including magnesium, potassium
and calcium) prior to each infusion and after completion of
treatment, until within normal limits—correct any
electrolyte disturbance promptly.
l DIRECTIONS FOR ADMINISTRATION Manufacturer advises
necitumumab should be given under the supervision of an
experienced specialist, in an environment where full
resuscitation facilities and resources for the treatment of
infusion-related reactions are immediately available.
l HANDLING AND STORAGE Manufacturer advises store in a
refrigerator (2–8ºC); consult product literature for storage
conditions after preparation of the infusion.
l PATIENT AND CARER ADVICE Manufacturer advises
patients and their carers should be made aware of the
symptoms of thromboembolism and advised to seek
medical attention if they experience sudden
breathlessness, chest pain, or swelling of a limb.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Necitumumab for untreated advanced or metastatic
squamous non-small-cell lung cancer (September 2016)
Necitumumab, in combination with gemcitabine and
cisplatin, is not recommended within its marketing
authorisation for adults with locally advanced or
metastatic epidermal growth factor receptor (EGFR)-
expressing squamous non-small-cell lung cancer that has
not been treated with chemotherapy.
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 clinician consider it
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
ELECTROLYTES: May contain Sodium
▶ Portrazza (Eli Lilly and Company Ltd) A
Necitumumab 16 mg per 1 ml Portrazza 800mg/50ml concentrate
for solution for infusion vials | 1 vial P £1,450.00 (Hospital only)
l DRUG ACTION Nivolumab is a human immunoglobulin G4
monoclonal antibody, which binds to the programmed
death-1 (PD-1) receptor thereby potentiating an immune
Melanoma (in combination with ipilimumab) (specialist
use only)| Advanced renal cell carcinoma (in
combination with ipilimumab) (specialist use only)
▶ Adult: (consult product literature)
Melanoma (as monotherapy) (specialist use only)|
Advanced renal cell carcinoma (as monotherapy)
▶ Adult: 240 mg every 2 weeks, alternatively 480 mg
every 4 weeks, consult product literature for
information on dose adjustments based on individual
patient safety and tolerability
Non-small cell lung cancer (as monotherapy) (specialist
use only)| Urothelial carcinoma (as monotherapy)
(specialist use only)| Squamous cell cancer of the head
and neck (as monotherapy) (specialist use only)|
Classical Hodgkin lymphoma (as monotherapy)
▶ Adult: 240 mg every 2 weeks, consult product literature
for information on dose adjustments based on
individual patient safety and tolerability
Adjuvant treatment of melanoma (as monotherapy)
▶ Adult: 3 mg/kg every 2 weeks, consult product
literature for information on dose adjustments based
on individual patient safety and tolerability
MHRA/CHM ADVICE: NIVOLUMAB (OPDIVO ®): REPORTS OF
ORGAN TRANSPLANT REJECTION (JULY 2017)
A European review of worldwide data concluded that
nivolumab may increase the risk of rejection in organ
transplant recipients. The MHRA recommends
considering the benefit of treatment with nivolumab
versus the risk of possible organ transplant rejection for
l CAUTIONS May increase risk of severe graft-versus-host
reaction in patients who have had prior haematopoietic
stem cell transplant (particularly in those with a prior
history). patients may need pre-medication to minimise
the development of infusion-related reactions
l INTERACTIONS → Appendix 1: monoclonal antibodies
inflammation . gastrointestinal disorders . hepatic
disorders . hypophysitis . hypopituitarism . metabolic
▶ Frequency not known Solid organ transplant rejection
SIDE-EFFECTS, FURTHER INFORMATION Immune-related
reactions Manufacturer advises that most immunerelated adverse reactions improved or resolved with
appropriate management, including initiation of
corticosteroids and treatment modifications—consult
product literature for further information.
BNF 78 Antibody responsive malignancy 873
Immune system and malignant disease
Infusion-related reactions Manufacturer advises that
patients with mild or moderate infusion reactions may
treatment if severe infusion reactions occur.
l CONCEPTION AND CONTRACEPTION Manufacturer advises
effective contraception required during treatment and for
at least 5 months after treatment in women of childbearing
l PREGNANCY Manufacturer advises avoid unless potential
benefit outweighs risk—toxicity in animal studies.
l BREAST FEEDING Manufacturer advises avoid—no
l HEPATIC IMPAIRMENT Manufacturer advises caution in
moderate to severe impairment (limited information
l MONITORING REQUIREMENTS Manufacturer advises
electrolyte disturbances before and periodically during
treatment. Patients should be monitored for adverse
reactions for at least 5 months after the last dose.
l DIRECTIONS FOR ADMINISTRATION Manufacturer advises
for intermittent intravenous infusion, give undiluted or
dilute to a concentration of not less than 1 mg/mL with
Glucose 5% or Sodium Chloride 0.9%; give over 30 or
60 minutes (depending on dose—consult product
literature) through an in-line filter (pore size
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 PATIENT AND CARER ADVICE Patients should be provided
with a patient alert card with each prescription.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Nivolumab for treating advanced (unresectable or metastatic)
melanoma (February 2016) NICE TA384
Nivolumab (Opdivo ®) as monotherapy is recommended,
within its marketing authorisation, as a treatment option
for advanced (unresectable or metastatic) melanoma in
www.nice.org.uk/guidance/ta384
▶ Nivolumab in combination with ipilimumab for treating
advanced melanoma (July 2016) NICE TA400
Nivolumab (Opdivo ®) in combination with ipilimumab is
recommended, within its marketing authorisation, as a
treatment option for advanced (unresectable or
metastatic) melanoma in adults, only if the manufacturer
provides ipilimumab with the discount agreed in the
www.nice.org.uk/guidance/ta400
▶ Nivolumab for adjuvant treatment of completely resected
melanoma with lymph node involvement or metastatic
disease (January 2019) NICE TA558
Nivolumab (Opdivo ®) is recommended for use within the
Cancer Drugs Fund as an option for the adjuvant
treatment of completely resected melanoma in adults with
lymph node involvement or metastatic disease. It is
recommended only if the conditions in the managed
access agreement are followed.
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/ta558
▶ Nivolumab for previously treated advanced renal cell
carcinoma (updated November 2017) NICE TA417
Nivolumab (Opdivo ®) is recommended, within its
marketing authorisation, as an option for previously
treated advanced renal cell carcinoma in adults, when the
manufacturer provides nivolumab in line with the
commercial access agreement with NHS England.
www.nice.org.uk/guidance/ta417
▶ Nivolumab for treating relapsed or refractory classical
Hodgkin lymphoma (updated November 2017) NICE TA462
Nivolumab (Opdivo ®) is recommended, within its
marketing authorisation, as an option for treating relapsed
or refractory classical Hodgkin lymphoma in adults after
autologous stem cell transplant and treatment with
brentuximab vedotin, when the manufacturer provides
nivolumab in line with the commercial access agreement
www.nice.org.uk/guidance/ta462
▶ Nivolumab for previously treated squamous non-small-cell
lung cancer (November 2017) NICE TA483
Nivolumab (Opdivo ®) is recommended for use within the
Cancer Drugs Fund as an option for treating locally
advanced or metastatic squamous non-small-cell lung
cancer in adults after chemotherapy, only if:
. nivolumab is stopped at 2 years of uninterrupted
treatment, or earlier in the event of disease progression,
. 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/ta483
▶ Nivolumab for previously treated non-squamous non-smallcell lung cancer (November 2017) NICE TA484
Nivolumab (Opdivo ®) is recommended for use within the
Cancer Drugs Fund as an option for treating locally
advanced or metastatic non-squamous non-small-cell
lung cancer in adults after chemotherapy, only if:
. their tumours are PD-L1 positive, and
. nivolumab is stopped at 2 years of uninterrupted
treatment, or earlier in the event of disease progression,
. 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/ta484
▶ Nivolumab for treating squamous cell carcinoma of the head
and neck after platinum-based chemotherapy (November
Nivolumab (Opdivo ®) is recommended for use within the
Cancer Drugs Fund as an option for treating squamous cell
carcinoma of the head and neck in adults whose disease
has progressed on platinum-based chemotherapy, only if:
. the disease has progressed within 6 months of having
. nivolumab is stopped at 2 years of uninterrupted
treatment, or earlier in the event of disease progression,
. 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
874 Antibody responsive malignancy BNF 78
Immune system and malignant disease
arrangements, until they and their NHS clinician consider
www.nice.org.uk/guidance/ta490
▶ Nivolumab for treating locally advanced unresectable or
metastatic urothelial cancer after platinum-containing
chemotherapy (July 2018) NICE TA530
Nivolumab (Opdivo ®) is not recommended, within its
marketing authorisation, for treating locally advanced
unresectable or metastatic urothelial carcinoma in adults
who have had platinum-containing therapy.
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/ta530
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (July 2016)
that nivolumab (Opdivo ®) is accepted for use within NHS
Scotland for the treatment of locally advanced or
metastatic squamous non-small cell lung cancer after prior
chemotherapy in adults. 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.
The Scottish Medicines Consortium has advised (October
2016) that nivolumab (Opdivo ®) is accepted for restricted
use within NHS Scotland for the treatment of locally
advanced or metastatic non-squamous non-small cell lung
cancer after prior chemotherapy in adults, subject to a
two-year clinical stopping rule. This advice is contingent
upon the continuing availability of the patient access
scheme in NHS Scotland or a list price that is equivalent or
The Scottish Medicines Consortium has advised (August
2016) that nivolumab (Opdivo ®) is accepted for restricted
use within NHS Scotland as monotherapy for the
treatment of advanced (unresectable or metastatic)
melanoma in adults previously untreated with ipilimumab.
This advice is contingent upon the continuing availability
of the patient access scheme in NHS Scotland or a list price
The Scottish Medicines Consortium has advised
(November 2016) that nivolumab (Opdivo ®) is accepted for
restricted use within NHS Scotland in combination with
ipilimumab for the first-line treatment of advanced
(unresectable or metastatic) melanoma in adults. This
advice is contingent upon the continuing availability of
the patient access scheme in NHS Scotland or a list price
The Scottish Medicines Consortium has advised
(December 2018) that nivolumab (Opdivo ®) is accepted for
use within NHS Scotland as monotherapy for the adjuvant
treatment of adults with melanoma with involvement of
lymph nodes or metastatic disease who have undergone
complete resection. 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.
The Scottish Medicines Consortium has advised (June
2017) that nivolumab (Opdivo ®) is accepted for use within
NHS Scotland as monotherapy for treating adults with
advanced renal cell carcinoma after prior therapy. The
advice is contingent upon the continuing availability of
the patient access scheme in NHS Scotland or a list price
The Scottish Medicines Consortium has advised (July
2017) that nivolumab (Opdivo ®) is accepted for use within
NHS Scotland for the treatment of patients with relapsed
or refractory classical Hodgkin lymphoma after autologous
stem cell transplant and treatment with brentuximab
vedotin. 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.
The Scottish Medicines Consortium has advised
(September 2017) that nivolumab (Opdivo ®) is accepted for
restricted use within NHS Scotland as monotherapy, for
the treatment of squamous cell cancer of the head and
neck in adults progressing on or after platinum-based
therapy. Treatment with nivolumab is subject to a two year
clinical stopping rule. 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.
The Scottish Medicines Consortium has advised (January
2018) that nivolumab (Opdivo ®) is not recommended for
use within NHS Scotland as monotherapy for the
treatment of locally advanced unresectable or metastatic
urothelial carcinoma in adults after failure of prior
platinum-containing therapy, as the economic case was
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 3
ELECTROLYTES: May contain Sodium
▶ Opdivo (Bristol-Myers Squibb Pharmaceuticals Ltd) A
Nivolumab 10 mg per 1 ml Opdivo 40mg/4ml concentrate for
solution for infusion vials | 1 vial P £439.00 (Hospital only)
Opdivo 100mg/10ml concentrate for solution for infusion vials | 1 vial P £1,097.00 (Hospital only)
Opdivo 240mg/24ml concentrate for solution for infusion vials | 1 vial P £2,633.00 (Hospital only)
Treatment of previously untreated chronic lymphocytic
Treatment of previously untreated advanced follicular
lymphoma | Treatment of follicular lymphoma in
patients who did not respond or who progressed during
or up to six months after treatment with rituximab or a
▶ Adult: (consult product literature or local protocols)
CONTRA-INDICATIONS, FURTHER INFORMATION
For obinutuzumab contra-indications, consult product
CAUTIONS, FURTHER INFORMATION For full details on the
cautions of obinutuzumab, consult product literature.
▶ Hepatitis B infection and reactivation Hepatitis B infection and
reactivation (including fatal cases) have been reported in
patients taking obinutuzumab. Patients with positive
hepatitis B serology should be referred to a liver specialist
for monitoring and initiation of antiviral therapy before
treatment initiation; treatment should not be initiated in
patients with evidence of current hepatitis B infection
until the infection has been adequately treated. Patients
should be closely monitored for clinical and laboratory
signs of active hepatitis B infection during treatment and
BNF 78 Antibody responsive malignancy 875
Immune system and malignant disease
for up to a year following the last infusion (consult product
l INTERACTIONS → Appendix 1: monoclonal antibodies
failure . hyperuricaemia . lymph node pain . nasal
complaints . pain . skin reactions . squamous cell
carcinoma .tumour lysis syndrome . urinary disorders . weight increased
▶ Frequency not known Acute coronary syndrome . angina
l CONCEPTION AND CONTRACEPTION Use effective
contraception during and for 18 months after treatment.
l PREGNANCY Avoid unless potential benefit outweighs risk
of B-lymphocyte depletion in fetus.
l BREAST FEEDING Avoid breast-feeding during and for
18 months after treatment—present in milk in animal
l MONITORING REQUIREMENTS Patients should be closely
monitored for clinical and laboratory signs of active
hepatitis B infection during treatment and for up to a year
following the last infusion (consult product literature).
l PRESCRIBING AND DISPENSING INFORMATION Infusion
related side-effects have been reported; Patients should
receive premedication with paracetamol, an
antihistamine, and a corticosteroid before each dose—
consult product literature for details.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Obinutuzumab in combination with chlorambucil for
untreated chronic lymphocytic leukaemia (June 2015)
Obinutuzumab (Gazyvaro ®), in combination with
chlorambucil, is an option for untreated chronic
lymphocytic leukaemia in patients who have comorbidities
that make full-dose fludarabine-based therapy unsuitable
. bendamustine-based therapy is not suitable and
. the manufacturer provides obinutuzumab with the
discount agreed in the patient access scheme.
Patients currently receiving obinutuzumab that is not
recommended according to the above criteria should have
the option to continue treatment until they and their
clinician consider it appropriate to stop.
www.nice.org.uk/guidance/ta343
▶ Obinutuzumab with bendamustine for treating follicular
lymphoma refractory to rituximab (August 2017) NICE TA472
Obinutuzumab (Gazyvaro ®) in combination with
bendamustine followed by obinutuzumab maintenance, is
recommended for use within the Cancer Drugs Fund as an
option for treating adults with follicular lymphoma that
did not respond or progressed during or up to six months
after treatment with rituximab or a rituximab-containing
regimen, only if the conditions in the managed access
agreement for obinutuzumab are followed.
www.nice.org.uk/guidance/ta472
▶ Obinutuzumab for untreated advanced follicular lymphoma
Obinutuzumab (Gazyvaro ®) is recommended as an option
for untreated advanced follicular lymphoma in adults (that
is, first as induction treatment with chemotherapy, then
alone as maintenance therapy), only if:
. the person has a Follicular Lymphoma International
Prognostic Index (FLIPI) score of 2 or more, and
. the manufacturer provides obinutuzumab with the
discount agreed in the patient access scheme.
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/ta513
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (March
2017) that obinutuzumab (Gazyvaro ®) is accepted for use
within NHS Scotland in combination with bendamustine
followed by obinutuzumab maintenance for the treatment
of patients with follicular lymphoma who did not respond
or who progressed during or up to six months after
treatment with rituximab or a rituximab-containing
regimen. 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.
The Scottish Medicines Consortium has advised
(September 2018) that obinutuzumab (Gazyvaro ®) is not
recommended for use within NHS Scotland in combination
with chemotherapy followed by obinutuzumab
maintenance therapy in patients achieving a response, for
the treatment of patients with previously untreated
advanced follicular lymphoma, as the economic case was
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Gazyvaro (Roche Products Ltd) A
Obinutuzumab 25 mg per 1 ml Gazyvaro 1000mg/40ml concentrate
for solution for infusion vials | 1 vial P £3,312.00 (Hospital only)
l DRUG ACTION Olaratumab is a monoclonal antibody that
binds to platelet-derived growth factor receptor alpha to
Advanced soft tissue sarcoma (in combination with
doxorubicin) in patients that are not amenable to
curative treatment with surgery or radiotherapy, and
who have not been previously treated with doxorubicin
▶ Adult: 15 mg/kg once daily on days 1 and 8 of a 3-week
cycle, for up to 8 cycles, patients whose disease has not
progressed after combination therapy may continue
with olaratumab monotherapy, for dose adjustments
due to side-effects and infusion-related reactions—
MHRA/CHM ADVICE: LARTRUVO ® (OLARATUMAB): NO NEW
PATIENTS TO BE PRESCRIBED DUE TO STUDY SHOWING NO
CLINICAL BENEFIT (FEBRUARY 2019)
Results from the clinical trial (ANNOUNCE) of
olaratumab with doxorubicin in patients with advanced
or metastatic soft tissue sarcoma showed no survival
benefit compared with doxorubicin. No new patients
should be prescribed Lartruvo ®, but treatment may be
continued in patients who experience clinical benefit
while further assessment of study results is ongoing.
l CAUTIONS Patients should receive pre-medication to
minimise the development of adverse reactions (consult
l INTERACTIONS → Appendix 1: monoclonal antibodies
876 Antibody responsive malignancy BNF 78
Immune system and malignant disease
SIDE-EFFECTS, FURTHER INFORMATION Side-effects were
reported for use of olaratumab in combination with
Infusion-related reactions Infusion related reactions
have been reported; for grade 1 or 2 infusion-related
reactions, manufacturer advises interrupt treatment and
treat as clinically indicated; treatment may be
recommenced at a reduced dose once the reaction has
resolved and pre-medication should be given prior to
subsequent infusions—consult product literature.
Permanently discontinue treatment in the event of a grade
3 or 4 infusion-related reaction.
l CONCEPTION AND CONTRACEPTION Manufacturer advises
women of child-bearing potential should use effective
contraception during and for at least 3 months after
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 and
for at least 3 months after stopping treatment—no
▶ Manufacturer advises monitor for signs and symptoms of
infusion-related reactions during the infusion.
▶ Manufacturer advises monitor neutrophil and platelet
count prior to each dose and during treatment; monitor
coagulation profile in patients with increased risk of
l DIRECTIONS FOR ADMINISTRATION Manufacturer advises
for intermittent intravenous infusion (Lartruvo ®), dilute
requisite dose to a final volume of 250 mL with Sodium
Chloride 0.9 %; give over approx. 60 minutes at a rate not
exceeding 25 mg/minute. Manufacturer advises
resuscitation facilities should be available.
l HANDLING AND STORAGE Manufacturer advises store in a
refrigerator (2–8 °C)—consult product literature for
storage conditions after preparation of the infusion.
Driving and skilled tasks Manufacturer advises patients and
carers should be counselled on the effects on driving and
performance of skilled tasks—increased risk of fatigue.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Olaratumab in combination with doxorubicin for treating
advanced soft tissue sarcoma (August 2017) NICE TA465
Olaratumab, in combination with doxorubicin, is
recommended for use within the Cancer Drugs Fund as an
option for advanced soft tissue sarcoma in adults, only if:
. they have not had any previous systemic chemotherapy
for advanced soft tissue sarcoma
. they cannot have curative treatment with surgery or
their disease does not respond to radiotherapy
. the conditions in the managed access agreement for
This recommendation is not intended to affect treatment
with olaratumab that was started in the NHS before this
guidance was published. Patients having treatment
outside this recommendation may continue without
change to the funding arrangements in place for them
before this guidance was published, until they and their
NHS clinician consider it appropriate to stop.
www.nice.org.uk/guidance/TA465
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (November
2017) that olaratumab (Lartruvo ®), in combination with
doxorubicin, is accepted for restricted use within NHS
Scotland for the first-line treatment of patients with
advanced soft-tissue sarcoma not amenable to curative
treatment with surgery or radiotherapy. This advice is
contingent upon the continuing availability of the patient
access scheme in NHS Scotland or a list price that is
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
▶ Lartruvo (Eli Lilly and Company Ltd) A
Olaratumab 10 mg per 1 ml Lartruvo 500mg/50ml concentrate for
solution for infusion vials | 1 vial P £1,000.00
Lartruvo 190mg/19ml concentrate for solution for infusion vials |
l DRUG ACTION Panitumumab is a monoclonal antibody
that binds to the epidermal growth factor receptor (EGFR).
Treatment of non-mutated RAS metastatic colorectal
cancer (combination therapy)| Treatment of nonmutated RAS metastatic colorectal cancer (monotherapy
after failure of fluoropyrimidine-, oxaliplatin-, and
irinotecan-containing chemotherapy regimens)
▶ Adult: (consult product literature)
MHRA/CHM ADVICE: SEVERE SKIN REACTIONS
Severe skin reactions have been reported very commonly
in patients treated with panitumumab. Patients
receiving panitumumab who have severe skin reactions
or develop worsening skin reactions should be
monitored for the development of inflammatory or
infectious sequelae (including cellulitis, sepsis, and
necrotising fasciitis). Appropriate treatment should be
promptly initiated and panitumumab withheld or
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
l CONTRA-INDICATIONS Interstitial pulmonary disease .the
combination of panitumumab with oxaliplatin-containing
chemotherapy is contra-indicated in patients with mutant
RAS metastatic colorectal cancer or for whom RAS status is
discontinue if interstitial lung disease develops .risk
factors for keratitis .risk factors for severe dry eye .risk
factors for ulcerative keratitis (including contact lens use)
l INTERACTIONS → Appendix 1: monoclonal antibodies
BNF 78 Antibody responsive malignancy 877
Immune system and malignant disease
▶ Uncommon Angioedema . cyanosis . infusion related
reaction . nasal dryness . onycholysis .respiratory disorders
▶ Rare or very rare Anaphylactic reaction . severe cutaneous
l CONCEPTION AND CONTRACEPTION Manufacturer advises
effective contraception during and for 6 months after
l PREGNANCY Avoid (toxicity in animal studies). See also
Comments
Post a Comment
اكتب تعليق حول الموضوع