MOA and CD30 testing
ADCETRIS mechanism of action and CD30 expression in lymphoma treatment
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ADCETRIS MOA
ADCETRIS: A CD30-targeted antibody-drug conjugate1
CD30 is a key biomarker in classical Hodgkin Lymphoma and certain peripheral T-cell lymphomas.1
ADCETRIS is part of a unique class of therapy known as antibody drug conjugates and is designed to target cells expressing CD30.1
Watch ADCETRIS MOA
See how ADCETRIS targets cells expressing CD30.1
Anticancer activity
Nonclinical data suggest that the anticancer activity of ADCETRIS acts via CD30-directed cytotoxicity and antibody-dependent cellular phagocytosis (ADCP). ADCETRIS can also harm normal cells.1 Use the buttons to switch between the proposed ADCETRIS MOAs.
Effector cell recruited via Fc-FcγR interactions
Engulfs and destroys target cell
1
2
3
4
1
ADCETRIS binds to CD30
2
ADCETRIS-CD30 complex is internalized
3
MMAE is released via proteolytic cleavage and binds to tubulin to disrupt microtubule network
4
Cell-cycle arrest and apoptosis
ADCETRIS
Antibody specific for CD301
MMAE, a microtubule-disrupting agent1
Protease-cleavable linker1
CD30 Biomarker
Testing CD30 expression quantitatively is important for diagnosis and treatment
- CD30 is a member of the tumor necrosis factor receptor family and is expressed on the surface of certain peripheral T-cell lymphomas (PTCLs), such as systemic anaplastic large cell lymphoma (sALCL) cells, and on Hodgkin Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL)1
- Quantitative testing for CD30 can aid in the differential diagnosis of certain lymphomas1,2
- Detection of CD30 can help identify patients who may be appropriate candidates for CD30-directed therapy1,2
Explore CD30 expression in cHL subtypes
CD30 is expressed in approximately 95% of all cases of cHL.2
Explore CD30 expression in PTCL subtypes
There are approximately 30 different subtypes of CD30-expressing PTCLs.8,9
ADCETRIS+CHP is approved for any level of CD30 expression (≥1%)1—ensure no eligible patient is overlooked
CD30 Testing in PTCLs
CD30 testing is critical for identifying patients with PTCLs eligible for ADCETRIS
- Expression of CD30 is reported inconsistently in pathology results (often binary [eg, positive/negative])24,25
- Eligible patients may be overlooked for treatment if the percentage expression is not reported1,24,25
CD30 expression should be reported as
a percentage for all PTCL subtypes
a percentage for all PTCL subtypes
Percentage stated
Any CD30 expression (≥1%) renders patients eligible for ADCETRIS1
Binary results
Qualitative reporting may miss patients with CD30 expression who qualify for ADCETRIS1,24,25
Ask pathologists to consistently report CD30 expression as a percentage for all PTCL subtypes
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 use effective contraception during ADCETRIS treatment and for 2 months after the last dose of ADCETRIS. Advise male patients with female partners of reproductive potential to use effective contraception during ADCETRIS treatment and for 4 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.
Please see full Prescribing Information, including BOXED WARNING, for 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.
Please see full Prescribing Information, including BOXED WARNING, for ADCETRIS.
- References:
- 1. ADCETRIS Prescribing Information. Bothell, WA: Seagen Inc.
- 2. Pileri SA, Ascani S, Leoncini L, et al. Hodgkin's lymphoma: the pathologist's viewpoint. J Clin Pathol. 2002;55:162-176.
- 3. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Nodular sclerosis classic Hodgkin lymphoma. Available at: https://seer.cancer.gov/seertools/hemelymph/51f6cf57e3e27c3994bd5372/. Accessed July 17, 2023.
- 4. Konkay K, Paul TR, Uppin SG, Rao DR. Hodgkin lymphoma: a clinicopathological and immunophenotypic study. Indian J Med Paediatr Oncol. 2016;37:59-65.
- 5. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Mixed cellularity classic Hodgkin lymphoma. Available at: https://seer.cancer.gov/seertools/hemelymph/51f6cf57e3e27c3994bd5342/. Accessed July 17, 2023.
- 6. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Lymphocyte-depleted classic Hodgkin lymphoma. Available at: https://seer.cancer.gov/seertools/hemelymph/51f6cf57e3e27c3994bd533f/. Accessed July 17, 2023.
- 7. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Lymphocyte-rich classic Hodgkin lymphoma. Available at: https://seer.cancer.gov/seertools/hemelymph/51f6cf57e3e27c3994bd5348/. Accessed July 17, 2023.
- 8. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127:2375-2390.
- 9. Hsi ED, Said J, Macon WR, et al. Diagnostic accuracy of a defined immunophenotypic and molecular genetic approach for peripheral T/NK-cell lymphomas. A North American PTCL Study Group Project. Am J Surg Pathol. 2014;38:768-775.
- 10. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Anaplastic large cell lymphoma, ALK-positive. Available at: https:// seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd52fd/. Accessed July 17, 2023.
- 11. National Cancer Institute. Anaplastic large cell lymphoma, ALK-negative. Available at: https://seer.cancer.gov/seertools/hemelymph/5a7dd4531ef55751804d309f/. Accessed July 17, 2023.
- 12. Delsol G, Falini B, Müller-Hermelink HK, et al. Anaplastic large cell lymphoma (ALCL), ALK-positive. In: Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC; 2008:312-316.
- 13. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Peripheral T-cell lymphoma, NOS. Available at: https://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd52e8/. Accessed July 17, 2023.
- 14. Federico M, Bellei M, Luminari S, et al. CD30+ expression in Peripheral T-cell lymphomas (PTCLs): A subset analysis from the international, prospective T-Cell Project. J Clin Oncol. 2015;33:8552.
- 15. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Angioimmunoblastic T-cell lymphoma. Available at: https://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd52dc/. Accessed July 17, 2023.
- 16. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Adult T-cell leukemia/lymphoma. Available at: https:// seer.cancer.gov/seertools/hemelymph/51f6cf59e3e27c3994bd544d/. Accessed July 17, 2023.
- 17. Campuzano-Zuluaga G, Pimentel A, Chapman-Fredricks JR, Ramos JC. Differential CD30 expression in adult T-cell leukemia-lymphoma subtypes. Retrovirology. 2014;11:P129.
- 18. Bossard C, Dobay MP, Parrens M, et al. Immunohistochemistry as a valuable tool to assess CD30 expression in peripheral T-cell lymphomas: high correlation with mRNA levels. Blood. 2014;124:2983-2986.
- 19. Lunning MA, Chiu A, Feldstein JT, et al. CD30 is a potential therapeutic target in patients with HTLV-1 associated adult T-cell leukemia/lymphoma presenting outside of Japan. Blood. 2012;120:2706.
- 20. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Enteropathy-associated T-cell lymphoma. Available at: https://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd5315/. Accessed July 17, 2023.
- 21. Sabattini E, Pizzi M, Tabanelli V, et al. CD30 expression in peripheral T-cell lymphomas. Haematologica. 2013;98:e81-e82.
- 22. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Extranodal NK-/T-cell lymphoma, nasal type. Available at: https://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd530f/. Accessed July 17, 2023.
- 23. Pongpruttipan T, Kummalue T, Bedavanija A, et al. Aberrant antigenic expression in extranodal NK/T-cell lymphoma: a multi-parameter study from Thailand. Diagn Pathol. 2011;6:79.
- 24. Weisenburger DD, Savage KJ, Harris NL, et al. Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project. Blood. 2011;117:3402-3408.
- 25. Jacobsen ED, Sharman JP, Oki Y, et al. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression. Blood. 2015;125:1394-1402.
Important Safety Information
Indications
Indications and 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 use effective contraception during ADCETRIS treatment and for 2 months after the last dose of ADCETRIS. Advise male patients with female partners of reproductive potential to use effective contraception during ADCETRIS treatment and for 4 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.
Please see full Prescribing Information, including BOXED WARNING, for 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.
Please see full Prescribing Information, including BOXED WARNING, for ADCETRIS.
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