– Company Leadership to Present 20 Abstracts in Oncology and Nine in Hematology Throughout Conference, Showcasing Takeda’s Unique Expertise in Blood Cancers and Bleeding Disorders –
CAMBRIDGE, Mass. & OSAKA, Japan-Friday 15 November 2019 [ AETOS Wire ]
(BUSINESS WIRE) -- Takeda Pharmaceutical Company Limited (TSE: 4502/NYSE:TAK) today announced that it will present a total of 29 company-sponsored abstracts at the 61st American Society of Hematology (ASH) Annual Meeting on December 7-10, 2019 in Orlando, FL, highlighting the company’s commitment to advancing the treatment of hematologic cancers and bleeding disorders.
Pursuing Breakthrough, Patient-Centric Innovation in Oncology and Bleeding Disorders
Takeda will present 29 scientific updates on the company’s investigational and early-stage therapies, which demonstrates its investment in new compounds to address patient needs, as well as data from Phase 3 trials and real-world evidence findings, in disease states including multiple myeloma, lymphoma and leukemia.
“We are presenting notable data on several clinical programs at ASH, highlighting our deep oncology pipeline and our commitment to developing innovative therapies that may address unmet needs for blood cancer patients,” said Phil Rowlands, Ph.D., Head, Oncology Therapeutic Area Unit, Takeda. “In particular we look forward to sharing data from the Phase 3 clinical trial of ixazomib in amyloidosis patients, data from the US MM-6 study, which evaluates an in-class transition from parenteral bortezomib to oral ixazomib in multiple myeloma, further analyses from the Phase 3 ECHELON-2 trial of ADCETRIS in peripheral T-cell lymphoma, as well as early stage data from several of our pipeline programs.”
In hematology, Takeda will present real-world evidence from studies of its portfolio of treatments across bleeding disorders, including hemophilia A, hemophilia B and von Willebrand disease. The company will also present scientific updates related to its hemophilia A and hemophilia B gene therapy programs and adeno-associated virus (AAV) gene therapy platform.
“Understanding real-world evidence is critical as Takeda continues to provide patients with innovative therapies for hemophilia A and hemophilia B while broadening our research and development efforts in von Willebrand disease and other bleeding disorders,” said Daniel Curran, M.D., Head, Rare Diseases Therapeutic Area Unit, Takeda. “Also at ASH, we look forward to providing an update on our gene therapy programs in hemophilia and the optimization of Takeda’s AAV gene therapy platform, particularly for patients with pre-existing immunity to AAV serotypes.”
Accepted oncology abstracts include:
Note: all times listed are in Eastern Standard Time
NINLARO™ (ixazomib) and Multiple Myeloma
Primary Results from the Phase 3 TOURMALINE-AL1 Trial of Ixazomib-Dexamethasone Versus Physician’s Choice of Therapy in Patients (Pts) with Relapsed/Refractory Primary Systemic AL Amyloidosis (RRAL). Abstract 139. Oral Presentation. Saturday, December 7, 9:30 a.m., Orange County Convention Center, Hall E1.
Closing the Efficacy and Effectiveness Gap: Outcomes in Relapsed/Refractory Multiple Myeloma (RRMM) Patients (Pts) Treated with Ixazomib-Lenalidomide-Dexamethasone (IRd) in Routine Clinical Practice Remain Comparable to the Outcomes Reported in the Phase 3 TOURMALINE-MM1 Study. Abstract 1845. Poster Presentation. Saturday, December 7, 5:30 – 7:30 p.m., Orange County Convention Center, Hall B.
Real-World (RW) Multiple Myeloma (MM) Patients (Pts) Remain Under-Represented in Clinical Trials Based on Standard Laboratory Parameters and Baseline Characteristics: Analysis of Over 3,000 Pts from the Insight MM Global, Prospective, Observational Study. Abstract 1887. Poster Presentation. Saturday, December 7, 5:30 – 7:30 p.m., Orange County Convention Center, Hall B.
Long-Term Proteasome Inhibitor (PI) Therapy in Community Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) Transitioning from Bortezomib (Btz)-Based to Ixazomib-Based Induction: Results from the US MM-6 Study in the Real World (RW) Setting. Abstract 1882. Poster Presentation. Saturday, December 7, 5:30 – 7:30 p.m., Orange County Convention Center, Hall B.
Real-World (RW) Treatment Patterns and Patient-Related Factors Including Quality of Life (QoL), Medication Adherence, and Actigraphy in Community Patients with Newly Diagnosed Multiple Myeloma (NDMM) Transitioning from Bortezomib (btz) to Ixazomib: The US MM-6 Community-Based Study. Abstract 3168. Poster Presentation. Sunday, December 8, 6:00 – 8:00 p.m., Orange County Convention Center, Hall B.
Comparative Effectiveness of Triplets Containing Bortezomib (V), Carfilzomib (K), or Ixazomib (I) Combined with a Lenalidomide and Dexamethasone Backbone (Rd) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM) in Routine Care in the United States (US). Abstract 1827. Poster Presentation. Saturday, December 7, 5:30 – 7:30 p.m., Orange County Convention Center, Hall B.
Evolving Real-World Treatment Patterns in Patients with Newly-Diagnosed Multiple Myeloma (NDMM) in the United States (U.S.). Abstract 3164. Poster Presentation. Sunday, December 8, 6:00 – 8:00 p.m., Orange County Convention Center, Hall B.
Evolving Treatment Trends in Relapsed/Refractory Multiple Myeloma (RRMM) in Europe from 2016 to 2018: Analysis of a Multi-National Survey. Abstract 3115. Poster Presentation. Sunday, December 8, 6:00 – 8:00 p.m., Orange County Convention Center, Hall B.
ADCETRIS® (brentuximab vedotin) and Lymphoma
Brentuximab Vedotin with Chemotherapy for Stage III/IV Classical Hodgkin Lymphoma (HL): 4-Year Update of the ECHELON-1 Study. Abstract 4026. Poster Presentation. Monday, December 9, 6:00 – 8:00 p.m., Orange County Convention Center, Hall B.
An Exploratory Analysis of Brentuximab Vedotin Plus CHP (A+CHP) in the Frontline Treatment of Patients with CD30+ Peripheral T-Cell Lymphomas (ECHELON-2): Impact of Consolidative Stem Cell Transplant. Abstract 464. Oral Presentation. Sunday, December 8, 12:15 p.m., Orange County Convention Center, Valencia D (W451D).
Patterns of Care and Clinical Outcomes in Peripheral T-Cell Lymphoma Patients Receiving First-Line Treatment in Routine Clinical Practice in France and the United Kingdom. Abstract 3482. Poster Presentation. Sunday, December 8, 6:00 – 8:00 p.m., Orange County Convention Center, Hall B.
Real-World Treatment Patterns and Overall Survival Among Medicare Fee-For-Service Beneficiaries Newly Diagnosed with Peripheral T-cell Lymphoma (PTCL). Abstract 3492. Poster Presentation. Sunday, December 8, 6:00 – 8:00 p.m., Orange County Convention Center, Hall B.
ICLUSIG® (ponatinib)
Major Adverse Cardiac, Arterial Occlusive, and Venous Occlusive Events Among Chronic Myeloid Leukemia Patients Prescribed Ponatinib Vs Bosutinib. Abstract 4751. Poster Presentation. Monday, December 9, 2019, 6:00 – 8:00 p.m., Orange County Convention Center, Hall B.
Pipeline (multiple myeloma, lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia)
A Phase 1 First-in-Human Study of the Anti-CD38 Dimeric Fusion Protein TAK-169 for the Treatment of Patients (pts) with Relapsed or Refractory Multiple Myeloma (RRMM) Who Are Proteasome Inhibitor (PI)- and Immunomodulatory Drug (IMiD)-Refractory, Including Pts Relapsed/Refractory (R/R) or Naïve to Daratumumab (dara). Abstract 1867. Poster Presentation. Saturday, December 7, 5:30 – 7:30 p.m., Orange County Convention Center, Hall B.
The Binding of CD38 Therapeutics to Red Blood Cells and Platelets Subverts Depletion of Target Cells. Abstract 3136. Poster Presentation. Sunday, December 8, 6:00 – 8:00 p.m., Orange County Convention Center, Hall B.
Preliminary Results from a Phase 1b Study of TAK-079, an Investigational Anti-CD38 Monoclonal Antibody (mAb) in Patients with Relapsed/ Refractory Multiple Myeloma (RRMM). Abstract 140. Oral Presentation. Saturday, December 7, 9:45 a.m., Orange County Convention Center, Hall E1.
Phase 1b/2 Study of TAK-981, a First-in-Class SUMOylation Inhibitor in Combination with Rituximab in Patients with Relapsed/Refractory (R/R) CD20-Positive Non-Hodgkin Lymphoma (NHL). Abstract 1593. Poster Presentation. Saturday, December 7, 5:30 – 7:30 p.m., Orange County Convention Center, Hall B.
Neddylation Pathway Regulates Treg Differentiation and T-Cell Function in Chronic Lymphocytic Leukemia (CLL) in Human Ex Vivo and Murine in Vivo Studies. Abstract 4313. Poster Presentation. Monday, December 9, 6:00 – 8:00 p.m., Orange County Convention Center, Hall B.
Pharmacologic Inhibition of SUMO-Activating Enzyme (SAE) with TAK981 Augments Interferon Signaling and Regulates T-Cell Differentiation in Ex Vivo Studies of Chronic Lymphocytic Leukemia (CLL). Abstract 1760. Poster Presentation. Saturday, December 7, 5:30 – 7:30 p.m., Orange County Convention Center, Hall B.
Targeting Hypersumoylation in Mantle Cell Lymphoma. Abstract 4060. Poster Presentation. Monday, December 9, 6:00 – 8:00 p.m., Orange County Convention Center, Hall B.
Accepted hematology abstracts include:
Note: all times listed are in Eastern Standard Time
ADYNOVATE® (Antihemophilic Factor (Recombinant), PEGylated) and Hemophilia A
Cost-Effectiveness Model of Recombinant FVIII Versus Emicizumab Treatment of Patients With Severe Hemophilia A Without Inhibitors. Abstract 2102. Poster Presentation. Saturday, December 7, 5:30 – 7:30 p.m., Orange County Convention Center, Hall B.
Real-World Age-Stratified FVIII Consumption and Bleed Outcomes Before and After Switching to Rurioctocog Alfa Pegol in a Retrospective, Observational Study Using US Specialty Pharmacy Data. Abstract 2411. Poster Presentation. Sunday, December 8, 6:00 – 8:00 p.m., Orange County Convention Center, Hall B.
FEIBA® (Anti-Inhibitor Coagulant Complex)
Real-World Clinical Management of Patients with Hemophilia and Inhibitors: Effectiveness and Safety of aPCC in Patients with >18 Months’ Follow-up in the FEIBA Global Outcome Study (FEIBA GO). Abstract 2418. Poster Presentation. Sunday, December 8, 6:00 – 8:00 p.m., Orange County Convention Center, Hall B.
von Willebrand Disease
Analysis of Bleeding and Treatment Patterns in Children and Adolescents before and after von Willebrand Disease Diagnosis Using Data from a US Medical Claims Database. Abstract 2117. Poster Presentation. Saturday, December 7, 5:30 – 7:30 p.m., Orange County Convention Center, Hall B.
Estimation of the Economic Burden Associated with Major Surgery Due to von Willebrand Disease Based on Claims Data from the USA. Abstract 4692. Poster Presentation. Monday, December 9, 6:00 – 8:00 p.m., Orange County Convention Center, Hall B.
Pipeline (hemophilia A, hemophilia B and gene therapies)
Co-Prevalence of Pre-Existing Immunity to Different Serotypes of Adeno-Associated Virus (AAV) in Adults with Hemophilia. Abstract 3349. Poster Presentation. Sunday, December 8, 6:00 – 8:00 p.m., Orange County Convention Center, Hall B.
Evaluation of the Human Factor IX Gene Therapy Vector TAK-748 in Hemophilia: Results from Non-Clinical Studies in Factor IX Knockout Mice and Rhesus Monkeys. Abstract 4633. Poster Presentation. Monday, December 9, 6:00 – 8:00 p.m., Orange County Convention Center, Hall B.
AAV8-Specific Immune Adsorption Column: A Treatment Option for Patients with Pre-Existing Anti-AAV8 Neutralizing Antibodies. Abstract 5922. Poster Presentation. Monday, December 9, 6:00 – 8:00 p.m., Orange County Convention Center, Hall B.
The Factor VIII Variant X5 Enhances Hemophilia A Gene Therapy Efficiency by Its Improved Secretion. Abstract 3356. Poster Presentation. Monday, December 9, 6:00 – 8:00 p.m., Orange County Convention Center, Hall B.
About ADCETRIS
ADCETRIS is an antibody-drug conjugate (ADC) comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics' proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells.
ADCETRIS injection for intravenous infusion has received FDA approval for six indications in adult patients with: (1) 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, (2) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine, (3) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (4) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (5) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (6) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.
Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-autologous stem cell transplantation (ASCT) consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression in 2017, adults with pcALCL or CD30-expressing MF who have had prior systemic therapy in 2018, and for previously untreated Stage IV Hodgkin lymphoma in combination with doxorubicin, vinblastine, and dacarbazine in 2019.
ADCETRIS received conditional marketing authorization from the European Commission in October 2012. The approved indications in Europe are: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (2) for the treatment of adult patients with relapsed or refractory sALCL, (3) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy and (5) for the treatment of adult patients with previously untreated CD30-positive Stage IV Hodgkin lymphoma in combination with AVD.
ADCETRIS has received marketing authorization by regulatory authorities in more than 70 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information below.
ADCETRIS is being evaluated broadly in more than 70 clinical trials, including a Phase 3 study in first-line Hodgkin lymphoma (ECHELON-1) and another Phase 3 study in first-line CD30-positive peripheral T-cell lymphomas (ECHELON-2), as well as trials in many additional types of CD30-positive malignancies.
Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.
ADCETRIS (brentuximab vedotin) Important Safety Information (European Union)
Please refer to Summary of Product Characteristics (SmPC) before prescribing.
CONTRAINDICATIONS
ADCETRIS is contraindicated for patients with hypersensitivity to brentuximab vedotin and its excipients. In addition, combined use of ADCETRIS with bleomycin causes pulmonary toxicity.
SPECIAL WARNINGS & PRECAUTIONS
Progressive multifocal leukoencephalopathy (PML): John Cunningham virus (JCV) reactivation resulting in progressive multifocal leukoencephalopathy (PML) and death can occur in patients treated with ADCETRIS. PML has been reported in patients who received ADCETRIS 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.
Closely monitor patients for new or worsening neurological, cognitive, or behavioral signs or symptoms, which may be suggestive 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 Hold dosing for any suspected case of PML and permanently discontinue ADCETRIS if a diagnosis of PML is confirmed.
Be alert to PML symptoms that the patient may not notice (e.g., cognitive, neurological, or psychiatric symptoms).
Pancreatitis: Acute pancreatitis has been observed in patients treated with ADCETRIS. Fatal outcomes have been reported. Closely monitor patients 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. Hold ADCETRIS for any suspected case of acute pancreatitis. ADCETRIS should be discontinued if a diagnosis of acute pancreatitis is confirmed.
Pulmonary Toxicity: Cases of pulmonary toxicity, some with fatal outcomes, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome (ARDS), have been reported in patients receiving ADCETRIS. Although a causal association with ADCETRIS has not been established, the risk of pulmonary toxicity cannot be ruled out. Promptly evaluate and treat new or worsening pulmonary symptoms (e.g., cough, dyspnoea) appropriately. Consider holding dosing during evaluation and until symptomatic improvement.
Serious infections and opportunistic infections: Serious infections such as pneumonia, staphylococcal bacteremia, sepsis/septic shock (including fatal outcomes), and herpes zoster, and opportunistic infections such as Pneumocystis jiroveci pneumonia and oral candidiasis have been reported in patients treated with ADCETRIS. Carefully monitor patients during treatment for emergence of possible serious and opportunistic infections.
Infusion-related reactions (IRR): Immediate and delayed IRR, as well as anaphylaxis, have been reported with ADCETRIS. Carefully monitor patients during and after an infusion. If anaphylaxis occurs, immediately and permanently discontinue administration of ADCETRIS and administer appropriate medical therapy. If an IRR occurs, interrupt the infusion and institute appropriate medical management. The infusion may be restarted at a slower rate after symptom resolution. Patients who have experienced a prior IRR should be premedicated for subsequent infusions. IRRs are more frequent and more severe in patients with antibodies to ADCETRIS.
Tumor lysis syndrome (TLS): TLS has been reported with ADCETRIS. Patients with rapidly proliferating tumor and high tumor burden are at risk of TLS. Monitor these patients closely and manage according to best medical practice.
Peripheral neuropathy (PN): ADCETRIS treatment may cause PN, both sensory and motor. ADCETRIS-induced PN is typically an effect of cumulative exposure to ADCETRIS and is reversible in most cases. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening PN may require a delay and a dose reduction or discontinuation of ADCETRIS.
Hematological toxicities: Grade 3 or Grade 4 anemia, thrombocytopenia, and prolonged (equal to or greater than one week) Grade 3 or Grade 4 neutropenia can occur with ADCETRIS. Monitor complete blood counts prior to administration of each dose.
Febrile neutropenia: Febrile neutropenia has been reported with ADCETRIS. Complete blood counts should be monitored prior to administration of each dose of treatment. Closely monitor patients for fever and manage according to best medical practice if febrile neutropenia develops.
When ADCETRIS is administered in combination with AVD, primary prophylaxis with G-CSF is recommended for all patients beginning with the first dose.
Stevens-Johnson syndrome (SJS): SJS and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. Fatal outcomes have been reported. Discontinue treatment with ADCETRIS if SJS or TEN occurs and administer appropriate medical therapy.
Gastrointestinal (GI) Complications: GI complications, some with fatal outcomes, including intestinal obstruction, ileus, enterocolitis, neutropenic colitis, erosion, ulcer, perforation and haemorrhage, have been reported with ADCETRIS. Promptly evaluate and treat patients if new or worsening GI symptoms occur.
Hepatotoxicity: Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been reported with ADCETRIS. Serious cases of hepatotoxicity, including fatal outcomes, have also occurred. Pre-existing liver disease, comorbidities, and concomitant medications may also increase the risk. Test liver function prior to treatment initiation and routinely monitor during treatment. Patients experiencing hepatotoxicity may require a delay, dose modification, or discontinuation of ADCETRIS.
Hyperglycemia: Hyperglycemia has been reported during trials in patients with an elevated body mass index (BMI) with or without a history of diabetes mellitus. Closely monitor serum glucose for patients who experiences an event of hyperglycemia. Administer anti-diabetic treatment as appropriate.
Renal and Hepatic Impairment: There is limited experience in patients with renal and hepatic impairment. Available data indicate that MMAE clearance might be affected by severe renal impairment, hepatic impairment, and by low serum albumin concentrations.
CD30+ CTCL: The size of the treatment effect in CD30 + CTCL subtypes other than mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL) is not clear due to lack of high level evidence. In two single arm phase II studies of ADCETRIS, disease activity has been shown in the subtypes Sézary syndrome (SS), lymphomatoid papulosis (LyP) and mixed CTCL histology. These data suggest that efficacy and safety can be extrapolated to other CTCL CD30+ subtypes. Carefully consider the benefit-risk per patient and use with caution in other CD30+ CTCL patient types.
Sodium content in excipients: This medicinal product contains 13.2 mg sodium per vial, equivalent to 0.7% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
INTERACTIONS
Patients who are receiving a strong CYP3A4 and P-gp inhibitor, concomitantly with ADCETRIS may have an increased risk of neutropenia. If neutropenia develops, refer to dosing recommendations for neutropenia (see SmPC section 4.2). Co-administration of ADCETRIS with a CYP3A4 inducer did not alter the plasma exposure of ADCETRIS, but it appeared to reduce plasma concentrations of MMAE metabolites that could be assayed. ADCETRIS is not expected to alter the exposure to drugs that are metabolized by CYP3A4 enzymes.
PREGNANCY: Advise women of childbearing potential to use two methods of effective contraception during treatment with ADCETRIS and until 6 months after treatment. There are no data from the use of ADCETRIS in pregnant women, although studies in animals have shown reproductive toxicity. Do not use ADCETRIS during pregnancy unless the benefit to the mother outweighs the potential risks to the fetus.
LACTATION (breast-feeding): There are no data as to whether ADCETRIS or its metabolites are excreted in human milk, therefore a risk to the newborn/infant cannot be excluded. With the potential risk, a decision should be made whether to discontinue breast-feeding or discontinue/abstain from therapy with ADCETRIS.
FERTILITY: In nonclinical studies, ADCETRIS treatment has resulted in testicular toxicity, and may alter male fertility. Advise men being treated with ADCETRIS not to father a child during treatment and for up to 6 months following the last dose.
Effects on ability to drive and use machines: ADCETRIS may have a moderate influence on the ability to drive and use machines.
UNDESIRABLE EFFECTS
Monotherapy: 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.
Combination Therapy: In the study of ADCETRIS as combination therapy with AVD in 662 patients with previously untreated advanced HL, 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. 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.
ADCETRIS (brentuximab vedotin) Important Safety Information (U.S.)
BOXED WARNING
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.
Contraindication
ADCETRIS concomitant with 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. Institute dose modifications accordingly.
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 patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL.
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 bacterial, fungal, or viral infections.
Tumor lysis syndrome: Closely monitor patients with rapidly proliferating tumor and high tumor burden.
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 compared to patients with normal renal function. 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 compared to patients with normal hepatic function. 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.
Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus, and to avoid pregnancy during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.
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