Safety Data

Safety Data¹

Pembrolizumab is most commonly associated with immune‑related adverse reactions. Most of these, including severe reactions, resolved following initiation of appropriate medical therapy or withdrawal of pembrolizumab (see “Description of selected adverse reactions” below).¹

The safety of pembrolizumab as monotherapy has been evaluated in 6,185 patients with advanced melanoma, resected Stage III melanoma (adjuvant therapy), NSCLC, cHL, urothelial carcinoma, HNSCC, or CRC across four doses (2 mg/kg bw every 3 weeks, 200 mg every 3 weeks, or 10 mg/kg bw every 2 or 3 weeks) in clinical studies. The frequencies included below and in Table 2 are based on all reported adverse drug reactions, regardless of the investigator assessment of causality. In this patient population, the median observation time was 7.6 months (range: 1 day to 47 months) and the most frequent adverse reactions with pembrolizumab were fatigue (32%), nausea (21%), and diarrhoea (21%). The majority of adverse reactions reported for monotherapy were of Grades 1 or 2 severity. The most serious adverse reactions were immune‑related adverse reactions and severe infusion‑related reactions.

The safety of pembrolizumab in combination with chemotherapy has been evaluated in 1,437 patients with NSCLC, HNSCC, or oesophageal carcinoma receiving 200 mg, 2 mg/kg bw or 10 mg/kg bw pembrolizumab every 3 weeks, in clinical studies. The frequencies included below and in Table 2 are based on all reported adverse drug reactions, regardless of the investigator assessment of causality. In this patient population, the most frequent adverse reactions were nausea (55%), anaemia (51%), fatigue (39%), constipation (37%), decreased appetite (34%), diarrhoea (33%), neutropenia (29%), and vomiting (28%). Incidences of Grades 3‑5 adverse reactions in patients with NSCLC were 67% for pembrolizumab combination therapy and 66% for chemotherapy alone, in patients with HNSCC were 85% for pembrolizumab combination therapy and 84% for chemotherapy plus cetuximab, and in patients with oesophageal carcinoma were 86% for pembrolizumab combination therapy and 83% for chemotherapy alone.

The safety of pembrolizumab in combination with axitinib has been evaluated in a clinical study of 429 patients with advanced RCC receiving 200 mg pembrolizumab every 3 weeks and 5 mg axitinib twice daily. In this patient population, the most frequent adverse reactions were diarrhoea (54%), hypertension (45%), fatigue (38%), hypothyroidism (35%), decreased appetite (30%), palmar‑plantar erythrodysaesthesia syndrome (28%), nausea (28%), ALT increased (27%), AST increased (26%), dysphonia (25%), cough (21%), and constipation (21%). Incidences of Grades 3‑5 adverse reactions were 76% for pembrolizumab combination therapy and 71% for sunitinib alone.

Tabulated list of adverse reactions

Adverse reactions observed in clinical studies of pembrolizumab as monotherapy or in combination with chemotherapy or other anti‑tumour medicines or reported from post‑marketing use of pembrolizumab are listed in Table 2. Adverse reactions known to occur with pembrolizumab or chemotherapies given alone may occur during treatment with these medicinal products in combination, even if these reactions were not reported in clinical studies with combination therapy. These reactions are presented by system organ class and by frequency. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); and not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Adverse reactions in patients treated with pembrolizumab*

	Monotherapy	Combination with chemotherapy	Combination with axitinib
Infections and infestations
Very common		pneumonia
Common	pneumonia		pneumonia
Blood and lymphatic system disorders
Very common	anaemia	anaemia, neutropenia, thrombocytopenia
Common	thrombocytopenia, neutropenia, lymphopenia	febrile neutropenia, leukopenia, lymphopenia	anaemia, neutropenia, leukopenia, thrombocytopenia
Uncommon	leukopenia, eosinophilia	eosinophilia	lymphopenia, eosinophilia
Rare	immune thrombocytopenia, haemolytic anaemia, pure red cell aplasia, haemophagocytic lymphohistiocytosis
Immune system disorders
Common	infusion–related reactiona	infusion–related reactiona	infusion–related reactiona
Uncommon	sarcoidosis
Not known	solid organ transplant rejection
Endocrine disorders
Very common	hypothyroidismb	hypothyroidism	hyperthyroidism, hypothyroidismb
Common	hyperthyroidism, thyroiditisc	hyperthyroidismd	hypophysitisf, thyroiditisc, adrenal insufficiencye
Uncommon	adrenal insufficiencye, hypophysitisf	hypophysitisf, adrenal insufficiencye, thyroiditisc
Metabolism and nutrition disorders
Very common	decreased appetite	hyponatraemia, hypokalaemia, decreased appetite	decreased appetite
Common	hyponatraemia, hypokalaemia, hypocalcaemia	hypocalcaemia	hypokalaemia, hyponatraemia, hypocalcaemia
Uncommon	type 1 diabetes mellitusg	type 1 diabetes mellitus	type 1 diabetes mellitusg
Psychiatric disorders
Very common		insomnia
Common	insomnia		insomnia
Nervous system disorders
Very common	headache	dizziness, neuropathy peripheral, headache	headache, dysgeusia
Common	dizziness, neuropathy peripheral, lethargy, dysgeusia	dysgeusia, lethargy	dizziness, lethargy, neuropathy peripheral
Uncommon	epilepsy	encephalitis, epilepsy	myasthenic syndromek
Rare	encephalitish, Guillain‑Barré syndromei, myelitisj, myasthenic syndromek, meningitis (aseptic)l	Guillain‑Barré syndrome
Eye disorders
Common	dry eye	dry eye	dry eye
Uncommon	uveitism		uveitism
Rare	Vogt‑Koyanagi‑Harada syndrome
Cardiac disorders
Common	cardiac arrhythmia† (including atrial fibrillation)	cardiac arrhythmia† (including atrial fibrillation)	cardiac arrhythmia† (including atrial fibrillation)
Uncommon	myocarditis, pericardial effusion, pericarditis	myocarditisn, pericardial effusion	myocarditis
Rare		pericarditis
Vascular disorders
Very common			hypertension
Common	hypertension	vasculitiso, hypertension
Rare	vasculitis
Respiratory, thoracic and mediastinal disorders
Very common	dyspnoea, cough	dyspnoea, cough	dyspnoea, cough, dysphonia
Common	pneumonitisp	pneumonitisp	pneumonitisp
Gastrointestinal disorders
Very common	diarrhoea, abdominal painq, nausea, vomiting, constipation	nausea, diarrhoea, vomiting, abdominal painq,constipation	diarrhoea, abdominal painq, nausea, vomiting, constipation
Common	colitisr, dry mouth	colitisr, dry mouth, gastritis	colitisr, dry mouth, gastritis
Uncommon	pancreatitiss, gastritis, gastrointestinal ulcerationt	pancreatitiss, gastrointestinal ulcerationt	pancreatitiss, gastrointestinal ulcerationt
Rare	small intestinal perforation
Hepatobiliary disorders
Common		hepatitisu	hepatitisu
Uncommon	hepatitisu
Rare	cholangitis sclerosing	cholangitis sclerosing
Skin and subcutaneous tissue disorders
Very common	rashv, pruritusw	rashv, alopecia, pruritusw	palmar‑plantar erythrodysaesthesia syndrome, rashv, pruritusw
Common	severe skin reactionsx, erythema, dermatitis, dry skin, vitiligoy, eczema, alopecia, dermatitis acneiform	severe skin reactionsx, dry skin, erythema,  dermatitis	severe skin reactionsx, dermatitis acneiform, dermatitis, dry skin, alopecia, eczema, erythema
Uncommon	psoriasis, lichenoid keratosisz, papule, hair colour changes	psoriasis, vitiligoy, eczema, dermatitis acneiform,  papule, lichenoid keratosis	hair colour changes, lichenoid keratosis, papule, psoriasis, vitiligoy
Rare	toxic epidermal necrolysis, Stevens‑Johnson syndrome, erythema nodosum	hair colour changes
Musculoskeletal and connective tissue disorders
Very common	musculoskeletal painaa, arthralgia	musculoskeletal painaa, arthralgia	musculoskeletal painaa, arthralgia, pain in extremity
Common	pain in extremity, myositisbb, arthritiscc	myositisbb, pain in extremity, arthritiscc	myositisbb, arthritiscc, tenosynovitisdd
Uncommon	tenosynovitisdd	tenosynovitisdd	Sjogren’s syndrome
Rare	Sjogren’s syndrome	Sjogren’s syndrome
Renal and urinary disorders
Common		acute kidney injury	acute kidney injury, nephritisee
Uncommon	nephritisee	nephritisee
Rare	cystitis noninfective
General disorders and administration site conditions
Very common	fatigue, asthenia, oedemaff, pyrexia	fatigue, asthenia, pyrexia, oedemaff	fatigue, asthenia, pyrexia
Common	influenza‑like illness, chills	influenza‑like illness, chills	oedemaff, influenza‑like illness, chills
Investigations
Very common		blood creatinine increased	alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased
Common	aspartate aminotransferase increased, alanine aminotransferase increased, hypercalcaemia, blood alkaline phosphatase increased, blood bilirubin increased, blood creatinine increased	aspartate aminotransferase increased, hypercalcaemia, alanine aminotransferase increased, blood alkaline phosphatase increased, blood bilirubin increased	blood alkaline phosphatase increased, hypercalcaemia, blood bilirubin increased
Uncommon	amylase increased	amylase increased	amylase increased

*Adverse reaction frequencies presented in Table 2 may not be fully attributable to pembrolizumab alone but may contain contributions from the underlying disease or from other medicinal products used in a combination.
†Based upon a standard query including bradyarrhythmias and tachyarrhythmias.

The following terms represent a group of related events that describe a medical condition rather than a single event:
a. infusion related reaction (drug hypersensitivity, anaphylactic reaction, anaphylactoid reaction, hypersensitivity and cytokine release syndrome)
b. hypothyroidism (myxoedema)
c. thyroiditis (autoimmune thyroiditis and thyroid disorder)
d. hyperthyroidism (Basedow’s disease)
e. adrenal insufficiency (Addison’s disease, adrenocortical insufficiency acute, secondary adrenocortical insufficiency)
f. hypophysitis (hypopituitarism)
g. type 1 diabetes mellitus (diabetic ketoacidosis)
h. encephalitis (autoimmune encephalitis)
i. Guillain Barré syndrome (axonal neuropathy and demyelinating polyneuropathy)
j. myelitis (including transverse myelitis)
k. myasthenic syndrome (myasthenia gravis, including exacerbation)
l. meningitis aseptic (meningitis, meningitis non infective)
m. uveitis (chorioretinitis, iritis and iridocyclitis)
n. myocarditis (autoimmune myocarditis)
o. vasculitis (central nervous system vasculitis)
p. pneumonitis (interstitial lung disease and organising pneumonia)
q abdominal pain (abdominal discomfort, abdominal pain upper and abdominal pain lower)
r .colitis (colitis microscopic, enterocolitis, enterocolitis haemorrhagic, autoimmune colitis, and immune-mediated enterocolitis)
s. pancreatitis (autoimmune pancreatitis and pancreatitis acute)
t. gastrointestinal ulceration (gastric ulcer and duodenal ulcer)
u. hepatitis (autoimmune hepatitis, immune mediated hepatitis, drug induced liver injury and acute hepatitis)
v. rash (rash erythematous, rash follicular, rash macular, rash maculo papular, rash papular, rash pruritic, rash vesicular and genital rash)
w. pruritus (urticaria, urticaria papular and pruritus genital)
x. severe skin reactions (dermatitis bullous, dermatitis exfoliative generalised, exfoliative rash, pemphigus, and Grade ≥ 3 of the following: acute febrile neutrophilic dermatosis, contusion, decubitus ulcer, dermatitis exfoliative, dermatitis psoriasiform, drug eruption, erythema multiforme, jaundice, lichen planus, oral lichen planus, pemphigoid, pruritus, pruritus genital, rash, rash erythematous, rash maculo papular, rash pruritic, rash pustular, skin lesion, skin necrosis and toxic skin eruption)
y. vitiligo (skin depigmentation, skin hypopigmentation and hypopigmentation of the eyelid)
z. lichenoid keratosis (lichen planus and lichen sclerosus)
aa. musculoskeletal pain (musculoskeletal discomfort, back pain, musculoskeletal stiffness, musculoskeletal chest pain and torticollis)
bb. myositis (myalgia, myopathy, necrotising myositis, polymyalgia rheumatica and rhabdomyolysis)
cc. arthritis (joint swelling, polyarthritis and joint effusion)
dd. tenosynovitis (tendonitis, synovitis and tendon pain)
ee. nephritis (autoimmune nephritis, tubulointerstitial nephritis and renal failure, renal failure acute, or acute kidney injury with evidence of nephritis, nephrotic syndrome, glomerulonephritis and glomerulonephritis membranous)
ff. oedema (oedema peripheral, generalised oedema, fluid overload, fluid retention, eyelid oedema and lip oedema, face oedema, localised oedema and periorbital oedema)

Description of selected adverse reactions

Data for the following immune related adverse reactions are based on patients who received pembrolizumab across four doses (2 mg/kg every 3 weeks, 10 mg/kg every 2 or 3 weeks, or 200 mg every 3 weeks) in clinical studies.

Immune related adverse reactions

Immune related pneumonitis

Pneumonitis occurred in 286 (4.6%) patients, including Grade 2, 3, 4 or 5 cases in 128 (2.1%), 73 (1.2%), 17 (0.3%) and 9 (0.1%) patients, respectively, receiving pembrolizumab. The median time to onset of pneumonitis was 3.5 months (range 2 days to 26.7 months). The median duration was 2.0 months (range 1 day to 33.0+ months). Pneumonitis occurred more frequently in patients with a history of prior thoracic radiation (8.2%) than in patients who did not receive prior thoracic radiation (4.2%). Pneumonitis led to discontinuation of pembrolizumab in 117 (1.9%) patients. Pneumonitis resolved in 166 patients, 4 with sequelae.

In patients with NSCLC, pneumonitis occurred in 160 (5.7%), including Grade 2, 3, 4 or 5 cases in 62 (2.2%), 47 (1.7%), 14 (0.5%) and 10 (0.4%), respectively. In patients with NSCLC, pneumonitis occurred in 8.9% with a history of prior thoracic radiation. In patients with cHL, the incidence of pneumonitis (all Grades) ranged from 5.2% to 10.8% for cHL patients in KEYNOTE-087 (n=210) and KEYNOTE-204 (n=148), respectively.

Immune related colitis

Colitis occurred in 121 (2.0%) patients, including Grade 2, 3 or 4 cases in 35 (0.6%), 67 (1.1%) and 5 (0.1%) patients, respectively, receiving pembrolizumab. The median time to onset of colitis was 4.7 months (range 7 days to 24.3 months). The median duration was 1.0 month (range 1 day to 12.4 months). Colitis led to discontinuation of pembrolizumab in 34 (0.5%) patients. Colitis resolved in 99 patients, 2 with sequelae. In patients with CRC treated with pembrolizumab as monotherapy (n=153), the incidence of colitis was 6.5% (all Grades) with 2.0% Grade 3 and 1.3% Grade 4.

Immune related hepatitis

Hepatitis occurred in 61 (1.0%) patients, including Grade 2, 3 or 4 cases in 8 (0.1%), 41 (0.7%) and 8 (0.1%) patients, respectively, receiving pembrolizumab. The median time to onset of hepatitis was 3.8 months (range 8 days to 26.3 months). The median duration was 1.1 months (range 1 day to 20.9+ months). Hepatitis led to discontinuation of pembrolizumab in 24 (0.4%) patients. Hepatitis resolved in 46 patients.

Immune related nephritis

Nephritis occurred in 25 (0.4%) patients, including Grade 2, 3 or 4 cases in 5 (0.1%), 15 (0.2%) and 2 (< 0.1%) patients, respectively, receiving pembrolizumab as monotherapy. The median time to onset of nephritis was 5.1 months (range 12 days to 21.4 months). The median duration was 3.3 months (range 6 days to 19.6 months). Nephritis led to discontinuation of pembrolizumab in 10 (0.2%) patients. Nephritis resolved in 15 patients, 4 with sequelae. In patients with non squamous NSCLC treated with pembrolizumab in combination with pemetrexed and platinum chemotherapy (n=488), the incidence of nephritis was 1.4% (all Grades) with 0.8% Grade 3 and 0.4% Grade 4.

Immune related endocrinopathies

Adrenal insufficiency occurred in 52 (0.8%) patients, including Grade 2, 3 or 4 cases in 23 (0.4%), 21 (0.3%) and 4 (0.1%) patients, respectively, receiving pembrolizumab. The median time to onset of adrenal insufficiency was 5.5 months (range 1 day to 23.7 months). The median duration was not reached (range 3 days to 32.4+ months). Adrenal insufficiency led to discontinuation of pembrolizumab in 5 (0.1%) patients. Adrenal insufficiency resolved in 18 patients, 5 with sequelae.

Hypophysitis occurred in 38 (0.6%) patients, including Grade 2, 3 or 4 cases in 15 (0.2%), 19 (0.3%) and 1 (< 0.1%) patients, respectively, receiving pembrolizumab. The median time to onset of hypophysitis was 5.9 months (range 1 day to 17.7 months). The median duration was 3.6 months (range 3 days to 30.4+ months). Hypophysitis led to discontinuation of pembrolizumab in 9 (0.1%) patients. Hypophysitis resolved in 17 patients, 8 with sequelae.

Hyperthyroidism occurred in 261 (4.2%) patients, including Grade 2 or 3 cases in 64 (1.0%) and 7 (0.1%) patients, respectively, receiving pembrolizumab. The median time to onset of hyperthyroidism was 1.4 months (range 1 day to 23.2 months). The median duration was 1.8 months (range 4 days to 27.6+ months). Hyperthyroidism led to discontinuation of pembrolizumab in 3 (< 0.1%) patients. Hyperthyroidism resolved in 207 (79.3%) patients, 5 with sequelae.

Hypothyroidism occurred in 699 (11.3%) patients, including Grade 2 or 3 cases in 510 (8.2%) and 7 (0.1%) patients, respectively, receiving pembrolizumab. The median time to onset of hypothyroidism was 3.4 months (range 1 day to 25.9 months). The median duration was not reached (range 2 days to 53.9+ months). Two patients (< 0.1%) discontinued pembrolizumab due to hypothyroidism. Hypothyroidism resolved in 171 (24.5%) patients, 14 with sequelae. In patients with cHL (n=389) the incidence of hypothyroidism was 17%, all of which were Grade 1 or 2. In patients with HNSCC treated with pembrolizumab as monotherapy (n=909), the incidence of hypothyroidism was 16.1% (all Grades) with 0.3% Grade 3. In patients with HNSCC treated with pembrolizumab in combination with platinum and 5 FU chemotherapy (n=276), the incidence of hypothyroidism was 15.2%, all of which were Grade 1 or 2.

Immune related skin adverse reactions

Immune related severe skin reactions occurred in 102 (1.6%) patients, including Grade 2, 3 or 5 cases in 11 (0.2%), 77 (1.2%) and 1 (< 0.1%) patients, respectively, receiving pembrolizumab. The median time to onset of severe skin reactions was 3.5 months (range 3 days to 25.5 months). The median duration was 1.9 months (range 1 day to 33.0+ months). Severe skin reactions led to discontinuation of pembrolizumab in 13 (0.2%) patients. Severe skin reactions resolved in 71 patients, 1 with sequelae.

Rare cases of SJS and TEN, some of them with fatal outcome, have been observed

Complications of allogeneic HSCT in cHL

Of 14 patients in KEYNOTE 013 who proceeded to allogeneic HSCT after treatment with pembrolizumab, 6 patients reported acute GVHD and 1 patient reported chronic GVHD, none of which were fatal. Two patients experienced hepatic VOD, one of which was fatal. One patient experienced engraftment syndrome post-transplant.

Of 32 patients in KEYNOTE 087 who proceeded to allogeneic HSCT after treatment with pembrolizumab, 16 patients reported acute GVHD and 7 patients reported chronic GVHD, two of which were fatal. No patients experienced hepatic VOD. No patients experienced engraftment syndrome post-transplant.

Of 14 patients in KEYNOTE 204 who proceeded to allogeneic HSCT after treatment with pembrolizumab, 8 patients reported acute GVHD and 3 patients reported chronic GVHD, none of which were fatal. No patients experienced hepatic VOD. One patient experienced engraftment syndrome post-transplant.

Elevated liver enzymes when pembrolizumab is combined with axitinib in RCC

In a clinical study of previously untreated patients with RCC receiving pembrolizumab in combination with axitinib, a higher than expected incidence of Grades 3 and 4 ALT increased (20%) and AST increased (13%) were observed. The median time to onset of ALT increased was 2.3 months (range: 7 days to 19.8 months). In patients with ALT ≥ 3 times ULN (Grades 2 4, n=116), ALT resolved to Grades 0 1 in 94%. Fifty nine percent of the patients with increased ALT received systemic corticosteroids. Of the patients who recovered, 92 (84%) were rechallenged with either pembrolizumab (3%) or axitinib (31%) monotherapy or with both (50%). Of these patients, 55% had no recurrence of ALT > 3 times ULN, and of those patients with recurrence of ALT > 3 times ULN, all recovered. There were no Grade 5 hepatic events.

Laboratory abnormalities

In patients treated with pembrolizumab monotherapy, the proportion of patients who experienced a shift from baseline to a Grade 3 or 4 laboratory abnormality was as follows: 10.8% for lymphocytes decreased, 8.3% for sodium decreased, 6.4% for haemoglobin decreased, 5.4% for phosphate decreased, 5.0% for glucose increased, 3.1% for AST increased, 3.0% for ALT increased, 2.7% for alkaline phosphatase increased, 2.4% for potassium decreased, 2.1% for neutrophils decreased, 2.0% for platelets decreased, 1.9% for calcium increased, 1.9% for potassium increased, 1.9% for bilirubin increased, 1.6% for albumin decreased, 1.5% for calcium decreased, 1.5% for creatinine increased, 0.9% for leucocytes decreased, 0.7% for magnesium increased, 0.6% for glucose decreased, 0.2% for magnesium decreased, and 0.2% for sodium increased.

In patients treated with pembrolizumab in combination with chemotherapy, the proportion of patients who experienced a shift from baseline to a Grade 3 or 4 laboratory abnormality was as follows: 33.0% for neutrophils decreased, 25.5% for lymphocytes decreased, 20.3% for haemoglobin decreased, 19.3% for leucocytes decreased, 13.9% for sodium decreased, 10.8% for platelets decreased, 9.7% for phosphate decreased, 8.4% for potassium decreased, 7.6% for glucose increased, 3.9% for AST increased, 3.8% for potassium increased, 3.7% for calcium decreased, 3.6% for ALT increased, 3.1% for creatinine increased, 3.0% for albumin decreased, 2.2% for calcium increased, 1.6% for alkaline phosphatase increased, 1.2% for bilirubin increased, 0.8% for glucose decreased, and 0.4% for sodium increased.

In patients treated with pembrolizumab in combination with axitinib, the proportion of patients who experienced a shift from baseline to a Grade 3 or 4 laboratory abnormality was as follows: 20.1% for ALT increased, 13.2% for AST increased, 10.8% for lymphocytes decreased, 8.9% for glucose increased, 7.8% for sodium decreased, 6.4% for phosphate decreased, 6.2% for potassium increased, 4.3% for creatinine increased, 3.6% for potassium decreased, 2.1% for bilirubin increased, 2.1% for haemoglobin decreased, 1.7% for alkaline phosphatase increased, 1.5% for prothrombin INR increased, 1.4% for leukocytes decreased, 1.4% for platelets decreased, 1.2% for activated partial thromboplastin time prolonged, 1.2% for neutrophils decreased, 1.2% for sodium increased, 0.7% for calcium decreased, 0.7% for calcium increased, 0.5% for albumin decreased, and 0.2% for glucose decreased.

Immunogenicity

In clinical studies in patients treated with pembrolizumab 2 mg/kg every three weeks, 200 mg every three weeks, or 10 mg/kg every two or three weeks as monotherapy, 36 (1.8%) of 2,034 evaluable patients tested positive for treatment emergent antibodies to pembrolizumab, of which 9 (0.4%) patients had neutralising antibodies against pembrolizumab. There was no evidence of an altered pharmacokinetic or safety profile with anti pembrolizumab binding or neutralising antibody development.

Paediatric population

The safety of pembrolizumab as monotherapy has been evaluated in 161 paediatric patients aged 9 months to 17 years with advanced melanoma, lymphoma, or PD L1 positive advanced, relapsed, or refractory solid tumours at 2 mg/kg every 3 weeks in the Phase I/II study KEYNOTE 051. The cHL population (n=22) included patients 11 to 17 years of age. The safety profile in paediatric patients was generally similar to that seen in adults treated with pembrolizumab. The most common adverse reactions (reported in at least 20% of paediatric patients) were pyrexia (33%), vomiting (30%), headache (26%), abdominal pain (22%), anaemia (21%), cough (21%) and constipation (20%). The majority of adverse reactions reported for monotherapy were of Grades 1 or 2 severity. Seventy six (47.2%) patients had 1 or more Grades 3 to 5 adverse reactions of which 5 (3.1%) patients had 1 or more adverse reactions that resulted in death. The frequencies are based on all reported adverse drug reactions, regardless of the investigator assessment of causality.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance.
Website: www.hpra.ie.