Trial assessing efficacy and safety of ADCETRIS® (brentuximab vedotin) in patients with relapsed sALCL1

ADCETRIS relapsed sALCL trial design

  • Single-agent ADCETRIS was evaluated in an open-label, single-arm, multicenter trial1
  • 58 patients with relapsed systemic anaplastic large cell lymphoma (sALCL) were enrolled1
  • ADCETRIS was administered 1.8 mg/kg intravenously over 30 minutes every 3 weeks for up to 16 cycles, or until disease progression or unacceptable toxicity.1, 4
  • Dose delays (of up to 3 weeks) and reductions (to 1.2 mg/kg) were allowed for toxicities2
  • Per protocol, patients who achieved stable disease or better as assessed by investigator should have received a minimum of 8 cycles of study treatment2
  • Assessment of efficacy included overall response rate (complete remission plus partial remission) and duration of response1
  • Response was evaluated by an independent review facility based on clinical and radiographic measures including computed tomography (CT) and positron-emission tomography (PET) as defined in the 2007 Revised Response Criteria for Malignant Lymphoma (modified)1,3

Study schema4

A line chart depicting 16 cycles of 21 days each, with a PET and CET scans at the beginning, and on cycles 4 and 7, and CT scans on cycles 2, 10, 13 and 16.
  • Patients remained on study drug until 16 cycles, disease progression, or unacceptable toxicity4
  • Computed tomography (CT) scans (chest, neck, abdomen, and pelvis) were performed at baseline and at cycles 2, 4, 7, 10, 13, and 164
  • Positron emission tomography (PET) scans were performed at baseline and at cycles 4 and 74

Patient demographics and baseline characteristics1,4

  N=58
Age, in years* 52 (14-76)
Gender 57% M/43% F
ECOG status
    0
    1
    2

19 (33%)
38 (66%)
1 (2%)
ALK-negative 42 (72%)
Relapsed 29 (50%)
Refractory to most recent treatment 29 (50%)
Prior auto-HSCT 15 (26%)

 

Median (range).
Protocol inclusion criterion required an ECOG PS (Eastern Cooperative Oncology Group Performance Status) of 0 or 1.
ECOG status of 2 was prohibited per protocol; patient was enrolled in violation.

 

Adapted from Pro B et al, 2012.

    View information on dosing and administration »

    View the efficacy and safety results for the relapsed sALCL trial »

    Please see Important Safety Information, including BOXED WARNING, and read full Prescribing Information.

    Seattle Genetics does not guarantee that enrollment will result in coverage and/or reimbursement.

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    © 2017 Seattle Genetics, Inc., Bothell, WA 98021. All rights reserved. USP-BVP-2016-0167(1)

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    Important Safety Information

    Indications

    ADCETRIS® (brentuximab vedotin) is indicated for treatment of patients with:

    Classical Hodgkin lymphoma (HL) after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates.

    Classical HL at high risk of relapse or progression as post auto-HSCT consolidation treatment.

    Systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen.

    The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

    Important Safety Information

    Boxed Warning

    Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS® (brentuximab vedotin).

    Contraindication:

    ADCETRIS is contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).

    Warnings and Precautions:

    • Peripheral neuropathy (PN): ADCETRIS treatment causes a PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness and institute dose modifications accordingly.
    • Anaphylaxis and infusion reactions: Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an infusion-related reaction occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Patients who experienced a prior infusion-related reaction should be premedicated for subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.
    • Hematologic toxicities: Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS. Febrile neutropenia has been reported with ADCETRIS. Monitor complete blood counts prior to each dose of ADCETRIS and consider more frequent monitoring 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 patients treated with ADCETRIS. Closely monitor patients during treatment for the emergence of possible 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 the use of ADCETRIS 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 the use of ADCETRIS in patients with moderate or severe hepatic impairment.
    • Hepatotoxicity: Serious cases of hepatotoxicity, including fatal outcomes, have occurred with ADCETRIS. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first dose of ADCETRIS or 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.
    • Progressive multifocal leukoencephalopathy (PML): 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 if PML is suspected and discontinue ADCETRIS if PML is confirmed.
    • Pulmonary toxicity: Events of noninfectious pulmonary toxicity including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, 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.
    • 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.
    • Gastrointestinal (GI) complications: Fatal and serious GI complications, including perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus, have been reported in ADCETRIS-treated patients. Lymphoma with preexisting GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, perform a prompt diagnostic evaluation and treat appropriately.
    • Embryo-fetal toxicity: Based on the mechanism of action and findings in animals, ADCETRIS can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should avoid pregnancy during ADCETRIS treatment and for at least 6 months after final dose of ADCETRIS.

    Adverse Reactions:

    In two uncontrolled single-arm trials of ADCETRIS as monotherapy in 160 patients with relapsed classical HL and sALCL, the most common adverse reactions (≥20%), regardless of causality, were: neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.

    In a placebo-controlled trial of ADCETRIS in 329 patients with classical HL at high risk of relapse or progression post auto-HSCT, the most common adverse reactions (≥20%) in the ADCETRIS-treatment arm (167 patients), regardless of causality, were: neutropenia, peripheral sensory neuropathy, thrombocytopenia, anemia, upper respiratory tract infection, fatigue, peripheral motor neuropathy, nausea, cough, and diarrhea.

    Drug Interactions:

    Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to monomethyl auristatin E (MMAE).

    Use in Specific Populations:

    MMAE exposure and adverse reactions are increased in patients with moderate or severe hepatic impairment or severe renal impairment. Avoid use.

    Advise females of reproductive potential to avoid pregnancy during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.

    Advise males with female sexual partners of reproductive potential to use effective contraception during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.

    Advise patients to report pregnancy immediately and avoid breastfeeding while receiving ADCETRIS.

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    Reference
    1.
    ADCETRIS [Prescribing Information]. Bothell, WA: Seattle Genetics, Inc.; September 2016.
    2.
    Data on file, Seattle Genetics, Inc.
    3.
    Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25:579-586.
    4.
    Pro B, Advani R, Brice P, et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol. 2012;30:2190-2196.