ADCETRIS® (brentuximab vedotin) is indicated for the treatment of pediatric patients 2 years and older with previously untreated high risk cHL, in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide.
Event-free survival: HR: 0.41 (95% CI: 0.25, 0.67); P = 0.0002; median follow-up: 42.1 months.1,2
AHOD1331 Trial Design: A randomized, open-label trial assessing the efficacy and safety of ADCETRIS+AVEPC vs ABVE-PC in 600 pediatric patients (2 to <22 years of age) with previously untreated high-risk cHL. High risk was defined as Ann Arbor Stage IIB with bulk disease, Stage IIIB, Stage IVA, and Stage IVB. Primary endpoint was event-free survival, defined as the time from randomization to the earliest of disease progression or relapse, second malignancy, or death due to any cause.1
*ADCETRIS will not work for everyone.
ABVE-PC = doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide; AVEPC =
doxorubicin, vincristine, etoposide, prednisone, cyclophosphamide; cHL = classical Hodgkin lymphoma; CI = confidence interval; HR = hazard ratio.
Study design
Efficacy
Safety
Dosage
*Does not apply to C86.2, C86.5, or C86.6.
ALCL = anaplastic large cell lymphoma; ALK = anaplastic lymphoma kinase; ATLL = adult T-cell leukemia/lymphoma; CPT = Current Procedural Terminology; CTCL = cutaneous T-cell lymphoma; HCPCS = Healthcare Common Procedure Coding System; HL = Hodgkin lymphoma; ICD-10-CM = International Classification of Diseases, Tenth Revision, Clinical Modification; MF = mycosis fungoides; NDC = National Drug Code; PTCL = peripheral T-cell lymphoma; PTCL-NOS = peripheral T-cell lymphoma, not otherwise specified.
References: 1. CMS.gov. ICD-10-CM tabular list of diseases and injuries. Centers for Medicare and Medicaid Services; 2019. https://www.cms.gov/Medicare/Coding/ICD10/Downloads/2019-ICD-10-CM-Tables-and-Index.zip. File name: icd10cm_tabular_2019.pdf. Accessed January 5, 2020. 2. ADCETRIS [Prescribing Information]. Bothell, WA: Seattle Genetics, Inc. October 2019. 3. CMS.gov. HCPCS codes. Centers for Medicare & Medicaid Services. https://www.cms.gov/Medicare/Coding/HCPCSReleaseCodeSets/Alpha-Numeric-HCPCS-Items/2020-Alpha-Numeric-HCPCS-File. File name: HCPC2020_ANWEB_w_disclaimer.xls. Accessed February 20, 2020. 4. American Medical Association. CPT 2019 Professional. Chicago, IL: American Medical Association; 2020.
AHOD1331: A randomized, phase 3, open-label, active-controlled trial in pediatric patients1,2
Selected inclusion criteria: Previously untreated high-risk cHL; ages 2 to <22 years; high risk was defined as Ann Arbor Stage IIB with bulk disease,* Stage IIIB, Stage IVA, and Stage IVB1
G-CSF was given as support for both arms.2
Primary endpoint: Event-free survival1
- Time from randomization to the earliest of disease progression or relapse, second malignancy, or death due to any cause
Selected baseline characteristics1
- Age: median 15 years (range: 3-21 years)
- <6 years: 1.5%
- 6 to <12 years: 13.5%
- 12 to <18 years: 74.7%
- ≥18 years: 10.3%
- Disease stage: 20% IIB with bulk disease, 19% IIIB, 29% IVA, 31% IVB
*Bulk tumor was defined as large mediastinal adenopathy (transverse tumor diameter more than one third the thoracic diameter at the dome of the diaphragm on a 1.83-meter posterior–anterior upright chest radiograph) or extramediastinal bulk (a continuous aggregate of nodal tissue outside the mediastinum that measured >6 cm in the transverse dimension on axial CT or the longest dimension on coronal or sagittal reformatted CT).2
†Dosage in AHOD1331: ADCETRIS+AVEPC arm: ADCETRIS 1.8 mg/kg over 30 minutes (day 1), doxorubicin 25 mg/m2 (days 1 and 2), vincristine 1.4 mg/m2 (day 8), etoposide 125 mg/m2 (days 1-3), prednisone 20 mg/m2 BID (days 1-7), cyclophosphamide 600 mg/m2 (days 1 and 2). ABVE-PC arm: doxorubicin 25 mg/m2 (days 1 and 2), bleomycin 5 units/m2 (day 1) and 10 units/m2 (day 8), vincristine 1.4 mg/m2 (days 1 and 8), etoposide 125 mg/m2 (days 1-3), prednisone 20 mg/m2 BID (days 1-7), cyclophosphamide 600 mg/m2 (days 1 and 2). Both arms received G-CSF. Each cycle was 21 days.1,2
‡ISRT (21 Gy) was prescribed after 5 cycles of systemic therapy for patients with LMA and to SRL with a 5PS of >3 at iPET; boost dose of 9 Gy was given to sites with incomplete metabolic response (5PS 3-5) at end of cycle 5.2
5PS = 5-point scale; BID = twice per day; CT = computed tomography; G-CSF = granulocyte colony–stimulating factor;
Gy = Gray; IMR = incomplete metabolic response; iPET = interim positron emission tomography;
ISRT = involved site radiation therapy; LMA = large mediastinal adenopathy; SRL = slowly responding lesion.
AHOD1331: A randomized, phase 3, open-label, active-controlled trial in pediatric patients1,2
Selected inclusion criteria: Previously untreated high-risk cHL; ages 2 to <22 years; high risk was defined as Ann Arbor Stage IIB with bulk disease,* Stage IIIB, Stage IVA, and Stage IVB1
G-CSF was given as support for both arms.2
Primary endpoint: Event-free survival1
- Time from randomization to the earliest of disease progression or relapse, second malignancy, or death due to any cause
Selected baseline characteristics1
- Age: median 15 years (range: 3-21 years)
- <6 years: 1.5%
- 6 to <12 years: 13.5%
- 12 to <18 years: 74.7%
- ≥18 years: 10.3%
- Disease stage: 20% IIB with bulk disease, 19% IIIB, 29% IVA, 31% IVB
*Bulk tumor was defined as large mediastinal adenopathy (transverse tumor diameter more than one third the thoracic diameter at the dome of the diaphragm on a 1.83-meter posterior–anterior upright chest radiograph) or extramediastinal bulk (a continuous aggregate of nodal tissue outside the mediastinum that measured >6 cm in the transverse dimension on axial CT or the longest dimension on coronal or sagittal reformatted CT).2
†Dosage in AHOD1331: ADCETRIS+AVEPC arm: ADCETRIS 1.8 mg/kg over 30 minutes (day 1), doxorubicin 25 mg/m2 (days 1 and 2), vincristine 1.4 mg/m2 (day 8), etoposide 125 mg/m2 (days 1-3), prednisone 20 mg/m2 BID (days 1-7), cyclophosphamide 600 mg/m2 (days 1 and 2). ABVE-PC arm: doxorubicin 25 mg/m2 (days 1 and 2), bleomycin 5 units/m2 (day 1) and 10 units/m2 (day 8), vincristine 1.4 mg/m2 (days 1 and 8), etoposide 125 mg/m2 (days 1-3), prednisone 20 mg/m2 BID (days 1-7), cyclophosphamide 600 mg/m2 (days 1 and 2). Both arms received G-CSF. Each cycle was 21 days.1,2
‡ISRT (21 Gy) was prescribed after 5 cycles of systemic therapy for patients with LMA and to SRL with a 5PS of >3 at iPET; boost dose of 9 Gy was given to sites with incomplete metabolic response (5PS 3-5) at end of cycle 5.2
5PS = 5-point scale; BID = twice per day; CT = computed tomography; G-CSF = granulocyte colony–stimulating factor;
Gy = Gray; IMR = incomplete metabolic response; iPET = interim positron emission tomography;
ISRT = involved site radiation therapy; LMA = large mediastinal adenopathy; SRL = slowly responding lesion.
ADCETRIS+AVEPC significantly improved event-free survival vs ABVE-PC1
Event-free survival (primary endpoint)1,2
- Median follow-up: 42.1 months (range: 0.1 to 80.9)2
- Median event-free survival was not reached in either arm1
A+AVEPC = ADCETRIS + doxorubicin, vincristine, etoposide, prednisone, cyclophosphamide.
Grade 3 or 4 adverse reactions reported in ≥2% of A+AVEPC–treated pediatric patients1
| ADCETRIS+AVEPC (n = 296), % of patients |
ABVE-PC (n = 297), % of patients |
|||||
| System Organ Class Preferred Term |
Grade 3 | Grade 4 | Grade 3 | Grade 4 | ||
| Blood and lymphatic system disorders | ||||||
| Anemia | 35 | 1.7 | 28 | 2 | ||
| Febrile neutropenia | 28 | 3.4 | 31 | 1.7 | ||
| Lymphopenia | 13 | 11 | 8 | 18 | ||
| Thrombocytopenia* | 10 | 22 | 11 | 16 | ||
| Neutropenia | 8 | 43 | 4.4 | 36 | ||
| Gastrointestinal disorders | ||||||
| Stomatitis | 10 | - | 7 | - | ||
| Nausea | 3.7 | - | 2 | - | ||
| Vomiting | 3.7 | - | 1.3 | - | ||
| Diarrhea | 2.4 | - | 0.3 | - | ||
| Colitis | 2 | 0.3 | 1 | - | ||
| Infections and infestations | ||||||
| Infections† | 9 | 2.7 | 7 | 3.4 | ||
| Nervous system disorders | ||||||
| Peripheral sensory neuropathy | 6 | - | 4.4 | - | ||
| Metabolism and nutrition disorders | ||||||
| Hypokalemia | 5 | 0.7 | 6 | 1 | ||
| Hyponatremia | 3.4 | - | 3 | - | ||
| Decreased appetite | 2.7 | - | 1.7 | - | ||
| Dehydration | 2.7 | - | 1 | - | ||
| Hepatobiliary disorders | ||||||
| Alanine aminotransferase increased | 3.7 | 0.3 | 2.7 | 0.3 | ||
| General disorders and administration site conditions | ||||||
| Infusion-related reactions‡ | 3 | 1 | 5 | 1 | ||
Serious adverse reactions occurred in 22% of patients who received ADCETRIS+AVEPC chemotherapy. Serious adverse reactions in >2% of patients included hypotension (3%) and febrile neutropenia (3%).1
*Includes thrombocytopenia and platelet count decreased.
†Includes sepsis, device related infection, skin infection, enterocolitis infectious, pneumonia, appendicitis, cellulitis, urinary tract infection, candida infection, mucosal infection, vaginal infection, wound infection, anorectal infection, arteritis infective, bacteremia, catheter site infection, clostridium difficile colitis, gastroenteritis norovirus, gingivitis, H1N1 influenza, herpes simplex reactivation, infective myositis, klebsiella bacteremia, klebsiella sepsis, meningitis, esophageal infection, oral candidiasis, osteomyelitis, otitis media, septic shock, serratia infection, sinusitis, soft tissue infection, staphylococcal infection, vulvitis.
‡Includes anaphylactic reaction, hypersensitivity, drug hypersensitivity, infusion related reaction, and bronchospasm.
Recommended ADCETRIS dosage and administration
Administer 1.8 mg/kg up to a maximum of 180 mg* in combination with chemotherapy every 3 weeks until a maximum of 5 doses1
Administer as an
intravenous infusion
over 30 minutes
Every 3 weeks
Administer G-CSF primary
prophylaxis beginning with
Cycle 1 of A+AVEPC
- Do not mix ADCETRIS with, or administer as an infusion with, other medicinal products1
*The dose for patients weighing greater than 100
kg should be calculated based on a weight of 100 kg.1
Recommended dosage in patients with renal impairment: No dosage adjustment is required for mild renal impairment (CrCL >50-80 mL/min) and moderate renal impairment (CrCL 30-50 mL/min). Avoid use in patients with severe (CrCL <30 mL/min) renal impairment.1
Recommended dosage in patients with hepatic impairment: Reduce the dosage of ADCETRIS to 1.2 mg/kg up to a maximum of 120 mg every 3 weeks for patients with mild hepatic impairment (Child-Pugh A). Avoid use in patients with moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment.1
Dose modifications for peripheral neuropathy in pediatric patients1
| Severity† |
Dose Modifications
|
|
Grade 2
|
|
|
Grade 3
|
|
| Grade 4 |
|
Dose modifications for neutropenia in pediatric patients1
| Severity |
Dose Modifications
|
| Grade 3 or 4 |
|
†Peripheral neuropathy was assessed using the Balis
Scale.1
G-CSF = granulocyte colony–stimulating factor.
Important Safety Information
Indications
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Indications
ADCETRIS® (brentuximab vedotin) is indicated for the treatment of:
Previously untreated Stage III/IV cHL
- Adult patients with previously untreated Stage III/IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine.
Previously untreated high risk cHL
- Pediatric patients 2 years and older with previously untreated high risk cHL, in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide.
cHL post-auto-HSCT consolidation
- Adult patients with cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation.
Relapsed cHL
- Adult patients with cHL after failure of auto-HSCT or after failure of at least two prior multi- agent chemotherapy regimens in patients who are not auto-HSCT candidates.
Previously untreated sALCL or other CD30-expressing PTCL
- Adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone.
Relapsed sALCL
- Adult patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen.
Relapsed pcALCL or CD30-expressing MF
- Adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30- expressing mycosis fungoides (MF) who have received prior systemic therapy.
Important Safety Information
BOXED WARNING
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.
CONTRAINDICATION
Contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).
WARNINGS AND PRECAUTIONS
- Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening PN may require a delay, change in dose, or discontinuation of ADCETRIS.
- Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.
- Hematologic toxicities: Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS.
- Administer G-CSF primary prophylaxis beginning with Cycle 1 for adult patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL, and pediatric patients who receive ADCETRIS in combination with chemotherapy for previously untreated high risk cHL.
- Monitor complete blood counts prior to each ADCETRIS dose. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.
- Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for infections.
- Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden may be at increased risk. Monitor closely and take appropriate measures.
- Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment. Avoid use in patients with severe renal impairment.
- Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment. Avoid use in patients with moderate or severe hepatic impairment.
- Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.
- PML: Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
- Pulmonary toxicity: Fatal and serious events of noninfectious pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, have been reported. Monitor patients for signs and symptoms, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement.
- Serious dermatologic reactions: Fatal and serious cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy.
- Gastrointestinal (GI) complications: Fatal and serious cases of acute pancreatitis have been reported. Other fatal and serious GI complications include perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. Lymphoma with preexisting GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, including severe abdominal pain, perform a prompt diagnostic evaluation and treat appropriately.
- Hyperglycemia: Serious cases, such as new-onset hyperglycemia, exacerbation of preexisting diabetes mellitus, and ketoacidosis (including fatal outcomes) have been reported with ADCETRIS. Hyperglycemia occurred more frequently in patients with high body mass index or diabetes. Monitor serum glucose and if hyperglycemia develops, administer anti-hyperglycemic medications as clinically indicated.
- Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of this potential risk, and to avoid pregnancy during ADCETRIS treatment and for 6 months after the last dose of ADCETRIS.
ADVERSE REACTIONS
The most common adverse reactions (≥20% in any study) are peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia, stomatitis, lymphopenia, mucositis, thrombocytopenia, and febrile neutropenia.
DRUG INTERACTIONS
Concomitant use of strong CYP3A4 inhibitors has the potential to affect the exposure to monomethyl auristatin E (MMAE). Closely monitor adverse reactions.
USE IN SPECIAL POPULATIONS
Lactation: Breastfeeding is not recommended during ADCETRIS treatment.
Females and Males of Reproductive Potential: Advise females to report pregnancy immediately and advise males with female sexual partners of reproductive potential to use effective contraception during ADCETRIS treatment and for 6 months after the last dose of ADCETRIS.
Indications
ADCETRIS® (brentuximab vedotin) is indicated for the treatment of:
Previously untreated Stage III/IV cHL
- Adult patients with previously untreated Stage III/IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine.
Previously untreated high risk cHL
- Pediatric patients 2 years and older with previously untreated high risk cHL, in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide.
cHL post-auto-HSCT consolidation
- Adult patients with cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation.
Relapsed cHL
- Adult patients with cHL after failure of auto-HSCT or after failure of at least two prior multi- agent chemotherapy regimens in patients who are not auto-HSCT candidates.
Previously untreated sALCL or other CD30-expressing PTCL
- Adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone.
Relapsed sALCL
- Adult patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen.
Relapsed pcALCL or CD30-expressing MF
- Adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30- expressing mycosis fungoides (MF) who have received prior systemic therapy.
Important Safety Information
BOXED WARNING
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.
CONTRAINDICATION
Contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).
WARNINGS AND PRECAUTIONS
- Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening PN may require a delay, change in dose, or discontinuation of ADCETRIS.
- Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.
- Hematologic toxicities: Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS.
- Administer G-CSF primary prophylaxis beginning with Cycle 1 for adult patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL, and pediatric patients who receive ADCETRIS in combination with chemotherapy for previously untreated high risk cHL.
- Monitor complete blood counts prior to each ADCETRIS dose. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.
- Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for infections.
- Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden may be at increased risk. Monitor closely and take appropriate measures.
- Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment. Avoid use in patients with severe renal impairment.
- Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment. Avoid use in patients with moderate or severe hepatic impairment.
- Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.
- PML: Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
- Pulmonary toxicity: Fatal and serious events of noninfectious pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, have been reported. Monitor patients for signs and symptoms, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement.
- Serious dermatologic reactions: Fatal and serious cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy.
- Gastrointestinal (GI) complications: Fatal and serious cases of acute pancreatitis have been reported. Other fatal and serious GI complications include perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. Lymphoma with preexisting GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, including severe abdominal pain, perform a prompt diagnostic evaluation and treat appropriately.
- Hyperglycemia: Serious cases, such as new-onset hyperglycemia, exacerbation of preexisting diabetes mellitus, and ketoacidosis (including fatal outcomes) have been reported with ADCETRIS. Hyperglycemia occurred more frequently in patients with high body mass index or diabetes. Monitor serum glucose and if hyperglycemia develops, administer anti-hyperglycemic medications as clinically indicated.
- Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of this potential risk, and to avoid pregnancy during ADCETRIS treatment and for 6 months after the last dose of ADCETRIS.
ADVERSE REACTIONS
The most common adverse reactions (≥20% in any study) are peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia, stomatitis, lymphopenia, mucositis, thrombocytopenia, and febrile neutropenia.
DRUG INTERACTIONS
Concomitant use of strong CYP3A4 inhibitors has the potential to affect the exposure to monomethyl auristatin E (MMAE). Closely monitor adverse reactions.
USE IN SPECIAL POPULATIONS
Lactation: Breastfeeding is not recommended during ADCETRIS treatment.
Females and Males of Reproductive Potential: Advise females to report pregnancy immediately and advise males with female sexual partners of reproductive potential to use effective contraception during ADCETRIS treatment and for 6 months after the last dose of ADCETRIS.
References: 1. ADCETRIS [Prescribing Information]. Bothell, WA: Seagen Inc. November 2022. 2. Castellino SM, Pei Q, Parsons SK, et al. Brentuximab vedotin with chemotherapy in pediatric high-risk Hodgkin's lymphoma. N Engl J Med. 2022;387:1649-1660.