Brentuximab vedotin interacts in the following cases:
Co-administration of brentuximab vedotin with ketoconazole, a strong CYP3A4 and P-gp inhibitor, increased the exposure to the antimicrotubule agent MMAE by approximately 73%, and did not alter the plasma exposure to brentuximab vedotin. Therefore, co-administration of brentuximab vedotin with strong CYP3A4 and P-gp inhibitors may increase the incidence of neutropenia.
If neutropenia develops during treatment it should be managed by dose delays. See the table below for appropriate dosing recommendations.
Dosing recommendations for neutropenia:
| Monotherapy | Combination therapy Note: Primary prophylaxis with G-CSF is recommended for all patients receiving combination therapy beginning with the first dose. | |
|---|---|---|
| Severity grade of neutropenia (signs and symptoms [abbreviated description of CTCAEa]) | Modification of dosing schedule | Modification of dosing schedule |
| Grade 1 (<LLN-1500/mm³ <LLN-1.5 × 109/L) or Grade 2 (<1500-1000/mm³ <1.5-1.0 × 109/L) | Continue with the same dose and schedule | Continue with the same dose and schedule |
| Grade 3 (<1,000-500/mm³ <1.0-0.5 × 109/L) or Grade 4 (<500/mm³ <0.5 × 109/L) | Withhold dose until toxicity returns to ≤ Grade 2 or baseline then resume treatment at the same dose and scheduleb. Consider G-CSF or GMCSF in subsequent cycles for patients who develop Grade 3 or Grade 4 neutropenia. | onsider G-CSF or GMCSF in subsequent cycles for patients who develop Grade 3 or Grade 4 neutropenia. |
a Grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0; see Neutrophils/granulocytes; LLN = lower limit of normal
b Patients who develop Grade 3 or Grade 4 lymphopenia may continue treatment without interruption.
Co-administration of brentuximab vedotin with rifampicin, a strong CYP3A4 inducer, did not alter the plasma exposure to brentuximab vedotin. Though PK data are limited, co administration of rifampicin appeared to reduce plasma concentrations of MMAE metabolites that could be assayed.
Patients with hepatic impairment should be closely monitored for adverse events. The recommended starting dose in patients with mild hepatic impairment is 0.9 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. There is no clinical trial experience using brentuximab in combination with chemotherapy in patients with hepatic impairment, where total bilirubin is >1.5 times the upper limit of normal (ULN) (unless due to Gilbert syndrome), or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) are >3 times the ULN, or >5 times the ULN if their elevation may be reasonably ascribed to the presence of HL in the liver. Use of brentuximab in combination with chemotherapy should be avoided in patients with moderate and severe hepatic impairment.
The recommended starting dose in patients with hepatic impairment is 1.2 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. Patients with hepatic impairment should be closely monitored for adverse events.
Patients with renal impairment should be closely monitored for adverse events. There is no clinical trial experience using brentuximab in combination with chemotherapy in patients with renal impairment, where serum creatinine is ≥2.0 mg/dL and/or creatinine clearance or calculated creatinine clearance is ≤40 mL/minute. Use of brentuximab in combination with chemotherapy should be avoided in patients with severe renal impairment.
The recommended starting dose in patients with severe renal impairment is 1.2 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. Patients with renal impairment should be closely monitored for adverse events.
In non-clinical studies, brentuximab vedotin treatment has resulted in testicular toxicity, and may alter male fertility. MMAE has been shown to have aneugenic properties. Therefore, men being treated with this medicine are advised to have sperm samples frozen and stored before treatment. Men being treated with this medicine are advised not to father a child during treatment and for up to 6 months following the last dose.
Gastrointestinal (GI) complications including intestinal obstruction, ileus, enterocolitis, neutropenic colitis, erosion, ulcer, perforation and haemorrhage, some with fatal outcomes, have been reported in patients treated with brentuximab vedotin. In the event of new or worsening GI symptoms, perform a prompt diagnostic evaluation and treat appropriately.
John Cunningham virus (JCV) reactivation resulting in progressive multifocal leukoencephalopathy (PML) and death can occur in brentuximab vedotin-treated patients. PML has been reported in patients who received this treatment after receiving multiple prior chemotherapy regimens. PML is a rare demyelinating disease of the central nervous system that results from reactivation of latent JCV and is often fatal.
Patients should be closely monitored for new or worsening neurological, cognitive, or behavioural signs or symptoms, which may be suggestive of PML. Brentuximab vedotin should be held for any suspected case of PML. Suggested evaluation of PML includes neurology consultation, gadolinium-enhanced magnetic resonance imaging of the brain and cerebrospinal fluid analysis for JCV DNA by polymerase chain reaction or a brain biopsy with evidence of JCV. A negative JCV PCR does not exclude PML. Additional follow up and evaluation may be warranted if no alternative diagnosis can be established. Brentuximab vedotin dosing should be permanently discontinued if a diagnosis of PML is confirmed.
The physician should be particularly alert to symptoms suggestive of PML that the patient may not notice (e.g., cognitive, neurological, or psychiatric symptoms).
Hepatotoxicity in the form of elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) has been reported with brentuximab vedotin. Serious cases of hepatotoxicity, including fatal outcomes, have also occurred. Pre-existing liver disease, comorbidities, and concomitant medications may also increase the risk. Liver function should be tested before initiating the treatment and routinely monitored in patients receiving brentuximab vedotin. Patients experiencing hepatotoxicity may require a delay, change in dose or discontinuation of brentuximab vedotin.
Acute pancreatitis has been observed in patients treated with brentuximab vedotin. Fatal outcomes have been reported.
Patients should be closely monitored for new or worsening abdominal pain, which may be suggestive of acute pancreatitis. Patient evaluation may include physical examination, laboratory evaluation for serum amylase and serum lipase, and abdominal imaging, such as ultrasound and other appropriate diagnostic measures. Brentuximab vedotin should be held for any suspected case of acute pancreatitis. Brentuximab vedotin should be discontinued if a diagnosis of acute pancreatitis is confirmed.
Tumour lysis syndrome (TLS) has been reported with brentuximab vedotin. Patients with rapidly proliferating tumour and high tumour burden are at risk of tumour lysis syndrome. These patients should be monitored closely and managed according to best medical practice. Management of TLS may include aggressive hydration, monitoring of renal function, correction of electrolyte abnormalities, anti-hyperuricaemic therapy, and supportive care.
Brentuximab vedotin may cause peripheral neuropathy, both sensory and motor. Brentuximab vedotin-induced peripheral neuropathy is typically an effect of cumulative exposure to this medicinal product and is reversible in most cases. In clinical trials, the majority of patients had resolution or improvement of their symptoms. Patients should be monitored for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paraesthesia, discomfort, a burning sensation, neuropathic pain or weakness. Patients experiencing new or worsening peripheral neuropathy may require a delay and a dose reduction of brentuximab vedotin or discontinuation of treatment.
If peripheral sensory or motor neuropathy emerges or worsens during treatment see the table below for appropriate dosing recommendations.
Dosing recommendations for new or worsening peripheral sensory or motor neuropathy:
| Monotherapy | Combination therapy | |
|---|---|---|
| Severity of peripheral sensory or motor neuropathy (signs and symptoms [abbreviated description of CTCAEa]) | Modification of dose and schedule | Modification of dose and schedule |
| Grade 1 (paraesthesia and/or loss of reflexes, with no loss of function) | Continue with the same dose and schedule | Continue with the same dose and schedule |
| Grade 2 (interfering with function but not with activities of daily living) or | Withhold dose until toxicity returns to ≤ Grade 1 or baseline, then restart treatment at a reduced dose of 1.2 mg/kg up to a maximum of 120 mg every 3 weeks | Reduce dose to 0.9 mg/kg up to a maximum of 90 mg every 2 weeks |
| Grade 3 (interfering with activities of daily living) | Withhold dose until toxicity returns to ≤ Grade 1 or baseline, then restart treatment at a reduced dose of 1.2 mg/kg every 3 weeks | Withhold treatment with ADCETRIS until toxicity is ≤ Grade 2, then restart treatment at a reduced dose to 0.9 mg/kg every 2 weeks. |
| Grade 4 (sensory neuropathy which is disabling or motor neuropathy that is life threatening or leads to paralysis) | Discontinue treatment | Discontinue treatment |
a Grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0; see neuropathy: motor; neuropathy: sensory; and neuropathic pain.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with brentuximab vedotin. Fatal outcomes have been reported. If SJS or TEN occur, brentuximab vedotin should be discontinued and appropriate medical therapy should be administered.
Serious infections such as pneumonia, staphylococcal bacteraemia, sepsis/septic shock (including fatal outcomes) and herpes zoster, cytomegalovirus (CMV) (reactivation) and opportunistic infections such as Pneumocystis jiroveci pneumonia and oral candidiasis have been reported in patients treated with brentuximab vedotin. Patients should be carefully monitored during treatment for the emergence of possible serious and opportunistic infections.
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infection with an absolute neutrophil count <1.0 × 109/L, fever ≥38.5°C; ref CTCAE v3) has been reported with treatment with brentuximab vedotin. Complete blood counts should be monitored prior to administration of each dose of treatment. Patients should be monitored closely for fever and managed according to best medical practice if febrile neutropenia develops.
In combination therapy with AVD, advanced age was a risk factor for febrile neutropenia.When brentuximab vedotin is administered in combination with AVD, primary prophylaxis with G-CSF is recommended for all patients regardless of age beginning with the first dose.
Cases of pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome (ARDS), some with fatal outcomes, have been reported in patients receiving brentuximab vedotin. Although a causal association with brentuximab vedotin has not been established, the risk of pulmonary toxicity cannot be ruled out. In the event of new or worsening pulmonary symptoms (e.g. cough, dyspnoea), a prompt diagnostic evaluation should be performed and patients should be treated appropriately. Consider holding brentuximab vedotin dosing during evaluation and until symptomatic improvement.
Grade 3 or Grade 4 anaemia, thrombocytopenia, and prolonged (≥1 week) Grade 3 or Grade 4 neutropenia can occur with brentuximab vedotin. Complete blood counts should be monitored prior to administration of each dose.
Hyperglycaemia has been reported during clinical trials in patients with an elevated Body Mass Index (BMI) with or without a history of diabetes mellitus. However, any patient who experiences an event of hyperglycaemia should have their serum glucose closely monitored. Anti-diabetic treatment should be administered as appropriate.
If neutropenia develops during treatment it should be managed by dose delays. See the table below for appropriate dosing recommendations.
Dosing recommendations for neutropenia:
| Monotherapy | Combination therapy Note: Primary prophylaxis with G-CSF is recommended for all patients receiving combination therapy beginning with the first dose. | |
|---|---|---|
| Severity grade of neutropenia (signs and symptoms [abbreviated description of CTCAEa]) | Modification of dosing schedule | Modification of dosing schedule |
| Grade 1 (<LLN-1500/mm³ <LLN-1.5 × 109/L) or Grade 2 (<1500-1000/mm³ <1.5-1.0 × 109/L) | Continue with the same dose and schedule | Continue with the same dose and schedule |
| Grade 3 (<1,000-500/mm³ <1.0-0.5 × 109/L) or Grade 4 (<500/mm³ <0.5 × 109/L) | Withhold dose until toxicity returns to ≤ Grade 2 or baseline then resume treatment at the same dose and scheduleb. Consider G-CSF or GMCSF in subsequent cycles for patients who develop Grade 3 or Grade 4 neutropenia. | onsider G-CSF or GMCSF in subsequent cycles for patients who develop Grade 3 or Grade 4 neutropenia. |
a Grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0; see Neutrophils/granulocytes; LLN = lower limit of normal
b Patients who develop Grade 3 or Grade 4 lymphopenia may continue treatment without interruption.
There are no data from the use of brentuximab vedotin in pregnant women. Studies in animals have shown reproductive toxicity.
Brentuximab vedotin should not be used during pregnancy unless the benefit to the mother outweighs the potential risks to the foetus. If a pregnant woman needs to be treated she should be clearly advised on the potential risk to the foetus.
See the fertility section below pertaining to advice for women whose male partners are being treated with Brentuximab vedotin.
There are no data as to whether brentuximab vedotin or its metabolites are excreted in human milk.
A risk to the newborn/infant cannot be excluded.
A decision should be made whether to discontinue breast-feeding or to discontinue/abstain from this therapy, taking into account a potential risk of breast-feeding for the child and the benefit of therapy for the woman.
In non-clinical studies, brentuximab vedotin treatment has resulted in testicular toxicity, and may alter male fertility. MMAE has been shown to have aneugenic properties. Therefore, men being treated with this medicine are advised to have sperm samples frozen and stored before treatment. Men being treated with this medicine are advised not to father a child during treatment and for up to 6 months following the last dose.
Brentuximab vedotin may have a moderate influence on the ability to drive and use machines (e.g. dizziness).
The safety profile of brentuximab vedotin is based on available clinical trial data, the Named Patient Program (NPP), and post-marketing experience to date. Frequencies of adverse reactions described below have been determined based on data generated from clinical studies.
In the pooled dataset of brentuximab vedotin as monotherapy across HL, sALCL and CTCL studies (SG035-0003, SG035-0004, SGN35-005, SGN35-006, C25001 and C25007) the most frequent adverse reactions (≥10%) were infections, peripheral sensory neuropathy, nausea, fatigue, diarrhoea, pyrexia, upper respiratory tract infection, neutropenia, rash, cough, vomiting, arthralgia, peripheral motor neuropathy, infusion-related reactions, pruritus, constipation, dyspnoea, weight decreased, myalgia and abdominal pain.
Serious adverse drug reactions occurred in 12% of patients. The frequency of unique serious adverse drug reactions was ≤1%.
Adverse events led to treatment discontinuation in 24% of patients receiving brentuximab vedotin.
The safety data in patients retreated with brentuximab vedotin (SGN35-006) were consistent with those observed in the combined pivotal phase 2 studies, with the exception of peripheral motor neuropathy, which had a higher incidence (28% vs. 9% in the pivotal phase 2 studies) and was primarily Grade 2. Patients also had a higher incidence of arthralgia, Grade 3 anaemia, and back pain compared to patients observed in the combined pivotal phase 2 studies.
The safety data in patients with relapsed or refractory HL who had not received an autologous stem cell transplant and were treated with the recommended dose of 1.8 mg/kg every three weeks in a single-arm phase 4 study (n=60), the phase 1 dose escalation and clinical pharmacology studies (n=15 patients) and in the NPP (n=26 patients) were consistent with the safety profile of the pivotal clinical studies.
For safety information of chemotherapy agents given in combination with brentuximab vedotin (doxorubicin, vinblastine and dacarbazine) for newly diagnosed patients with HL, refer to their summary of product characteristics.
In the study of brentuximab vedotin as combination therapy with AVD in 662 patients with previously untreated advanced HL (C25003), the most common adverse reactions (≥10%) were: neutropenia, nausea, constipation, vomiting, fatigue, peripheral sensory neuropathy, diarrhoea, pyrexia, alopecia, peripheral motor neuropathy, decreased weight, abdominal pain, anaemia, stomatitis, febrile neutropenia, bone pain, insomnia, decreased appetite, cough, headache, arthralgia, back pain, dyspnoea, myalgia, upper respiratory tract infection, alanine aminotransferase increased.
In patients receiving brentuximab vedotin combination therapy, serious adverse reactions occurred in 36% of patients. Serious adverse reactions occurring in ≥3% of patients included febrile neutropenia (17%), pyrexia (6%), and neutropenia (3%).
Adverse events led to treatment discontinuation in 13% of patients. Adverse events that led to treatment discontinuation in ≥2% of patients included peripheral sensory neuropathy, peripheral neuropathy, and peripheral motor neuropathy.
Adverse reactions for brentuximab vedotin are listed by MedDRA System Organ Class and Preferred Term. Within each System Organ Class, adverse reactions are listed under frequency categories of: 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); 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 to brentuximab vedotin:
| System organ class | Adverse reactions (monotherapy) | Adverse reactions (combination therapy) |
|---|---|---|
| Infections and infestations | ||
| Very common: | Infectiona, upper respiratory tract infection | Infectiona, upper respiratory tract infection |
| Common: | Herpes zoster, pneumonia, herpes simplex, oral candidiasis | Pneumonia, oral candidiasis, sepsis/septic shock, herpes simplex |
| Uncommon: | Pneumocystis jiroveci pneumonia, staphylococcal bacteraemia, cytomegalovirus infection or reactivation, sepsis/septic shock | Herpes zoster, Pneumocystis jiroveci pneumonia |
| Frequency not known: | Progressive multifocal leukoencephalopathy | |
| Blood and lymphatic system disorders | ||
| Very common: | Neutropenia | Neutropeniaa, anaemia, febrile neutropenia |
| Common: | Anaemia, thrombocytopenia | Thrombocytopenia |
| Uncommon: | Febrile neutropenia | |
| Immune system disorders | ||
| Uncommon: | Anaphylactic reaction | Anaphylactic reaction |
| Metabolism and nutrition disorders | ||
| Very common: | Decreased appetite | |
| Common: | Hyperglycaemia | Hyperglycaemia |
| Uncommon: | Tumour lysis syndrome | Tumour lysis syndrome |
| Nervous system disorders | ||
| Very common: | Peripheral sensory neuropathy, peripheral motor neuropathy | Peripheral sensory neuropathy, peripheral motor neuropathya, dizziness |
| Common: | Dizziness | |
| Uncommon: | Demyelinating polyneuropathy | |
| Respiratory, thoracic and mediastinal disorders | ||
| Very common: | Cough, dyspnoea | Cough, dyspnoea |
| Gastro-intestinal disorders | ||
| Very common: | Nausea, diarrhoea vomiting, constipation, abdominal pain | Nausea, constipation, vomiting, diarrhoea, abdominal pain, stomatitis |
| Uncommon: | Pancreatitis acute | Pancreatitis acute |
| Hepatobiliary disorders | ||
| Very common: | Alanine aminotransferase (ALT) increased | |
| Common: | Alanine aminotransferase/aspartate aminotransferase (ALT/AST) increased | Alanine aminotransferase/aspartate aminotransferase (ALT/AST) increased |
| Skin and subcutaneous tissue disorders | ||
| Very common: | Rasha, pruritus | Alopecia, rasha |
| Common: | Alopecia | Pruritus |
| Uncommon: | Stevens-Johnson syndrome/toxic epidermal necrolysis | Stevens-Johnson syndromeb |
| Musculoskeletal and connective tissue disorders | ||
| Very common: | Arthralgia, myalgia | Bone pain, arthralgia, back pain, myalgia |
| Common: | Back pain | |
| General disorders and administration site conditions | ||
| Very common: | Fatigue, pyrexia, infusion-related reactionsa | Fatigue, pyrexia |
| Common: | Chills | Infusion-related reactionsa, chills |
| Investigations | ||
| Very common: | Weight decreased | Weight decreased |
| Psychiatric Disorders | ||
| Very common: | Insomnia | |
a Represents pooling of preferred terms.
b Toxic epidermal necrolysis was not reported in the combination therapy setting.
In clinical trials, neutropenia led to dose delays in 14% of patients. Grade 3 neutropenia was reported in 13% and Grade 4 neutropenia was reported in 5% of patients. No patients required dose reduction or discontinued treatment for neutropenia.
Severe and prolonged (≥1 week) neutropenia can occur with this treatment which may increase the risk of patients developing serious infections. Febrile neutropenia reported in <1% of the patients.
In the pivotal phase 2 population (SG035-0003 and SG035-0004), the median duration of Grade 3 or Grade 4 neutropenia was limited (1 week); 2% of patients had Grade 4 neutropenia that lasted ≥7 days. Less than half of the patients in the pivotal phase 2 population with Grade 3 or Grade 4 neutropenia had temporally associated infections, and the majority of temporally associated infections were Grade 1 or Grade 2.
In the clinical trial of brentuximab vedotin as combination therapy, neutropenia led to dose delays in 24% of patients. Grade 3 neutropenia was reported in 18% and Grade 4 neutropenia was reported in 47% of patients. Two percent of patients required dose reduction and <1% discontinued one of more of the study drugs due to neutropenia.
Febrile neutropenia was reported in 21% of the patients who did not receive primary prophylaxis with G-CSF. The frequency of febrile neutropenia was 11% in patients who received primary prophylaxis with G-CSF.
In clinical trials, serious infections and opportunistic infections occurred in 10% of patients, sepsis or septic shock occurred in <1% of the patients. The most commonly reported opportunistic infections were herpes zoster and herpes simplex.
In the clinical trial of brentuximab vedotin as combination therapy, serious infections including opportunistic infections occurred in 15% of patients; sepsis, neutropenic sepsis, septic shock or bacteraemia occurred in 4% of the patients. The most commonly reported opportunistic infections were herpes viral infections.
In clinical trials treatment emergent neuropathy occurred in 59% of the population, peripheral motor neuropathy occurred in 14% of patients. Peripheral neuropathy led to treatment discontinuation in 15%, dose reductions in 15%, and dose delays in 17% of patients. For patients who experienced peripheral neuropathy the median time of onset of peripheral neuropathy was 12 weeks. The median duration of treatment for patients who discontinued due to peripheral neuropathy was 12 cycles.
Among patients who experienced peripheral neuropathy in the pivotal phase 2 studies (SG035-0003 and SG035-0004) and randomised phase 3 monotherapy studies (SGN35-005 and C25001), the median follow up time from end of treatment until last evaluation ranged from 48.9 to 98 weeks. At the time of last evaluation, most of the patients (82-85%) who experienced peripheral neuropathy had resolution or improvement of their peripheral neuropathy symptoms. The median time from onset to resolution or improvement for all events ranged from 16 to 23.4 weeks.
In patients with relapsed or refractory HL or sALCL who were retreated with brentuximab vedotin (SGN35-006), the majority of patients (80%) also had improvement or resolution of their peripheral neuropathy symptoms at the time of last evaluation.
In the clinical trial of brentuximab vedotin as combination therapy, treatment emergent neuropathy occurred in 67% of the population; peripheral motor neuropathy occurred in 11% of patients. Peripheral neuropathy led to treatment discontinuation in 7%, dose reductions in 21%, and dose delays in 1% of patients. For patients who experienced peripheral neuropathy the median time of onset of peripheral neuropathy was 8 weeks. Patients who discontinued due to peripheral neuropathy received a median of 8 doses of brentuximab vedotin+AVD (A+AVD) before discontinuation of one or more agents.
Among patients who experienced peripheral neuropathy, the median follow up time from end of treatment until last evaluation was approximately 91 weeks. At the time of last evaluation, most of the patients (76%) who experienced peripheral neuropathy had resolution or improvement of their peripheral neuropathy symptoms. The median time from onset to resolution or improvement of peripheral neuropathy events was 10 weeks (ranged from 0 weeks to 139 weeks).
IRRs, such as headache, rash, back pain, vomiting, chills, nausea, dyspnoea, pruritus and cough were reported in 13% of patients. Anaphylactic reactions have been reported. Symptoms of an anaphylactic reaction may include, but are not limited to, urticaria, angioedema, hypotension and bronchospasm. h4. Combination therapy
IRRs, such as headache, rash, back pain, vomiting, chills, nausea, dyspnoea, pruritus, cough, infusion site pain and pyrexia were reported in 9% of patients. Anaphylactic reactions have been reported. Symptoms of an anaphylactic reaction may include, but are not limited to, urticaria, angioedema, hypotension and bronchospasm.
In clinical trials, patients were periodically tested for antibodies to brentuximab vedotin using a sensitive electrochemiluminescent immunoassay. There was a higher incidence of infusion-related reactions observed in patients with antibodies to brentuximab vedotin relative to patients who tested transiently positive or negative.
The presence of antibodies to brentuximab vedotin did not correlate with a clinically meaningful reduction in serum brentuximab vedotin levels and did not result in a decrease in the efficacy of brentuximab vedotin. While the presence of antibodies to brentuximab vedotin does not necessarily predict the development of an IRR, there was a higher incidence of IRRs observed in patients with persistently positive anti-drug antibodies (ADA) relative to patients with transiently positive ADA and never positive ADA.
There was a trend of increased clearance of brentuximab vedotin in paediatric patients confirmed positive for ADAs. No patients aged <12 years (0 of 11) and 2 patients aged ≥12 years (2 of 23) became persistently ADA positive. Paediatric population Safety was evaluated in a phase ½ study in paediatric patients aged 7-17 years of age (n=36) with relapsed or refractory (r/r) HL and sALCL. In this study in 36 patients, no new safety concerns were reported.
The safety profile in elderly patients was consistent with that of adult patients.
In older patients (≥60 years of age; n=83 [13%]), the incidence of adverse events was similar across treatment arms. More serious adverse events and dose modifications (including dose delays, reductions, and discontinuations) were reported in the older patients compared with the overall study population. Advanced age was a risk factor for febrile neutropenia in patients in both arms. Older patients who received G-CSF primary prophylaxis had lower incidence of neutropenia and febrile neutropenia than those who did not receive G-CSF primary prophylaxis.
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