Calendar
Advanced Practice Providers Oncology Summit
The goal of this summit is to foster collaboration , share best practices , and provide a forum for peer-to-peer interaction among advanced practice providers who are actively engaged in caring for oncology patients . Find more info at apponcologysummit . mededmanager . com .
Upcoming Dates and Locations :
February 9 – 10 , 2018 Orlando , FL
April 6 – 7 , 2018 Dallas / Fort Worth , TX
May 4 – 5 , 2018 Cleveland , OH
March 9 – 10 , 2018 Boston , MA
April 20 – 21 , 2018 Seattle , WA
July 13 – 14 , 2018 Philadelphia , PA
Orlando , FL
ADCETRIS ® ( brentuximab vedotin ) for injection , for intravenous use Brief Summary : see package insert for complete prescribing information
WARNING : PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY ( PML )
JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS .
1 INDICATIONS AND USAGE
ADCTERIS is a CD30-directed antibody-conjugate indicated for treatment of adult patients with primary cutaneous anaplastic large cell lymphoma ( pcALCL ) or CD30- expressing mycosis fungoides ( MF ) who have received prior systemic therapy .
2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosage
Administer ADCETRIS as an intravenous infusion over 30 minutes every 3 weeks until a maximum of 16 cycles , disease progression , or unacceptable toxicity .
The recommended dose is 1.8 mg / kg up to a maximum of 180 mg . Reduce the dose in patients with mild hepatic impairment ( Child-Pugh A ) to 1.2 mg / kg up to a maximum of 120 mg . Avoid use in patients with moderate ( Child-Pugh B ) or severe ( Child-Pugh C ) hepatic impairment or severe renal impairment ( creatinine clearance [ CrCL ] < 30 mL / min ). The dose for patients weighing greater than 100 kg should be calculated based on a weight of 100 kg .
2.2 Dose Modification
Peripheral Neuropathy : For new or worsening Grade 2 or 3 peripheral neuropathy , hold dosing until improvement to baseline or Grade 1 . Restart at 1.2 mg / kg up to a maximum of 120 mg . For Grade 4 peripheral neuropathy , the dosing should be discontinued . The dose for patients weighing greater than 100 kg should be calculated based on a weight of 100 kg .
Neutropenia : For Grade 3 or 4 neutropenia , hold dosing until improvement to baseline or Grade 2 or lower . Consider G-CSF prophylaxis for subsequent cycles . In patients with recurrent Grade 4 neutropenia despite G-CSF prophylaxis , consider discontinuation or dose reduction to 1.2 mg / kg up to a maximum of 120 mg . The dose for patients weighing greater than 100 kg should be calculated based on a weight of 100 kg .
4 CONTRAINDICATIONS
ADCETRIS is contraindicated with concomitant bleomycin due to pulmonary toxicity ( e . g ., interstitial infiltration and / or inflammation ).
5 WARNINGS AND PRECAUTIONS 5.1 Peripheral Neuropathy
ADCETRIS treatment causes a peripheral neuropathy that is predominantly sensory . Cases of peripheral motor neuropathy have also been reported . ADCETRIS-induced peripheral neuropathy is cumulative .
In studies of ADCETRIS as monotherapy , 62 % of patients experienced any grade of neuropathy . The median time to onset of any grade was 13 weeks ( range , 0-52 ). Of the patients who experienced neuropathy , 62 % had complete resolution , 24 % had partial improvement , and 14 % had no improvement at the time of their last evaluation . The median time from onset to resolution or improvement of any grade was 21 weeks ( range , 0-195 ). Of the patients who reported neuropathy , 38 % had residual neuropathy at the time of their last evaluation [ Grade 1 ( 27 %), Grade 2 ( 9 %), Grade 3 ( 2 %)].
Monitor patients for symptoms of neuropathy , such as hypoesthesia , hyperesthesia , paresthesia , discomfort , a burning sensation , neuropathic pain , or weakness . Patients experiencing new or worsening peripheral neuropathy may require a delay , change in dose , or discontinuation of ADCETRIS .
5.2 Anaphylaxis and Infusion Reactions
Infusion-related reactions , including anaphylaxis , have occurred with ADCETRIS . Monitor patients during infusion . If anaphylaxis occurs , immediately and permanently discontinue administration of ADCETRIS and administer appropriate medical therapy . If an infusion-related reaction occurs , interrupt the infusion and institute appropriate medical management . Patients who have experienced a prior infusion-related reaction should be premedicated for subsequent infusions . Premedication may include acetaminophen , an antihistamine , and a corticosteroid .
5.3 Hematologic Toxicities
Prolonged ( ≥1 week ) severe neutropenia and Grade 3 or Grade 4 thrombocytopenia or anemia can occur with ADCETRIS . Febrile neutropenia has been reported with treatment with ADCETRIS . Monitor complete blood counts prior to each dose of ADCETRIS . 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 ADCETRIS doses .
5.4 Serious Infections and Opportunistic Infections
Serious infections and opportunistic infections such as pneumonia , bacteremia , and sepsis or septic shock ( including fatal outcomes ) have been reported in patients treated with ADCETRIS . Monitor patients closely during treatment for the emergence of possible bacterial , fungal , or viral infections .
5.5 Tumor Lysis Syndrome
Patients with rapidly proliferating tumor and high tumor burden may be at increased risk of tumor lysis syndrome . Monitor closely and take appropriate measures .
5.6 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 . Due to higher MMAE exposure , ≥Grade 3 adverse reactions may be more frequent in patients with severe renal impairment compared to patients with normal renal function . Avoid the use of ADCETRIS in patients with severe renal impairment ( CrCL < 30 mL / min ).
5.7 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 and severe hepatic impairment compared to patients with normal hepatic function . Avoid the use of ADCETRIS in patients with moderate ( Child-Pugh B ) or severe ( Child-Pugh C ) hepatic impairment .
5.8 Hepatotoxicity
Serious cases of hepatotoxicity , including fatal outcomes , have occurred in patients receiving ADCETRIS . Cases were consistent with hepatocellular injury , including elevations of transaminases and / or bilirubin . Cases have occurred after the first dose of ADCETRIS or after ADCETRIS rechallenge . Preexisting liver disease , elevated baseline liver enzymes , and concomitant medications may also increase the risk . Monitor liver enzymes and bilirubin . Patients experiencing new , worsening , or recurrent hepatotoxicity may require a delay , change in dose , or discontinuation of ADCETRIS .
5.9 Progressive Multifocal Leukoencephalopathy
JC virus infection resulting in PML and death has been reported in ADCETRIS-treated patients . First onset of symptoms occurred at various times from initiation of ADCETRIS therapy , 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 the diagnosis of PML in any patient presenting with new-onset signs and symptoms of central nervous system abnormalities . Hold ADCETRIS dosing for any suspected case of PML and discontinue ADCETRIS dosing if a diagnosis of PML is confirmed .
5.10 Pulmonary Toxicity
Events of noninfectious pulmonary toxicity including pneumonitis , interstitial lung disease , and acute respiratory distress syndrome ( ARDS ), some with fatal outcomes , have been reported . Monitor patients for signs and symptoms of pulmonary toxicity , including cough and dyspnea . In the event of new or worsening pulmonary symptoms , hold ADCETRIS dosing during evaluation and until symptomatic improvement .
5.11 Serious Dermatologic Reactions
Stevens-Johnson syndrome ( SJS ) and toxic epidermal necrolysis ( TEN ), including fatal outcomes , have been reported with ADCETRIS . If SJS or TEN occurs , discontinue ADCETRIS and administer appropriate medical therapy .
5.12 Gastrointestinal Complications
Acute pancreatitis , including fatal outcomes , has been reported . Other fatal and serious gastrointestinal ( 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 .
5.13 Embryo-Fetal Toxicity
Based on the mechanism of action and findings in animals , ADCETRIS can cause fetal harm when administered to a pregnant woman . There are no adequate and well-controlled studies of ADCETRIS in pregnant women . Brentuximab vedotin caused embryo-fetal toxicities , including significantly decreased embryo viability and fetal malformations , in animals at maternal exposures that were similar to the clinical dose of 1.8 mg / kg every three weeks .
Advise females of reproductive potential to avoid pregnancy during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS . If ADCETRIS is used during pregnancy or if the patient becomes pregnant during ADCETRIS treatment , the patient should be apprised of the potential risk to the fetus .
6 ADVERSE REACTIONS 6.1 Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions , adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice .
Across the clinical trials of ADCETRIS as monotherapy ( Studies 1-4 ), the most common adverse reactions ( ≥20 %) in ADCETRIS-treated patients were peripheral sensory neuropathy , fatigue , nausea , diarrhea , neutropenia , upper respiratory tract infection , and pyrexia .
pcALCL and CD30-expressing MF ( Study 4 : ALCANZA )
ADCETRIS was studied in 131 patients with pcALCL or CD30-expressing MF requiring systemic therapy in a randomized , open-label , multicenter clinical trial in which the recommended starting dose and schedule was ADCETRIS 1.8 mg / kg intravenously over 30 minutes every 3 weeks or physician ’ s choice of either methotrexate 5 to 50 mg orally weekly or bexarotene 300 mg / m 2 orally daily .