Efficacy summary: Extended PFS and OS

ADCETRIS+CHP significantly improved progression-free survival (PFS) and overall survival (OS) vs CHOP1,2

  • More than double the median PFS: 48.2 months (95% CI: 35.2, NE) for A+CHP vs 20.8 months (95% CI: 12.7, 47.6) for CHOP1

*Event defined as time from randomization to progression, death due to any cause, or receipt of subsequent anticancer therapy to treat residual or progressive disease.

CI = confidence interval; HR = hazard ratio; IRF = independent review facility; NE = not estimable.

ADCETRIS+CHP (A+CHP) more than doubled median progression-free survival (PFS) vs CHOP1

Kaplan-Meier Curve of IRF-Assessed PFS (Primary Endpoint)1

  • PFS was defined as time from randomization to progression, death due to any cause, or receipt of subsequent anticancer therapy to treat residual or progressive disease1
  • Median PFS: 48.2 months (95% CI: 35.2, NE) for A+CHP vs 20.8 months (95% CI: 12.7, 47.6) for CHOP1
  • Exploratory analyses demonstrated that PFS trended in favor of the A+CHP arm for most subgroups. ECHELON-2 was not powered to compare efficacy in individual subgroups1

CHOP = cyclophosphamide, doxorubicin, vincristine, prednisone; CI = confidence interval; HR = hazard ratio; IRF = independent review facility; NE = not estimable.

A+CHP demonstrated significantly longer overall survival (OS) vs CHOP1

Kaplan-Meier Curve of Overall Survival (Key Secondary Endpoint)1

  • Median overall survival follow-up of 42.1 months with A+CHP and CHOP; median overall survival not reached in either treatment arm2
  • Exploratory analyses demonstrated that overall survival trended in favor of the A+CHP arm for most subgroups. ECHELON-2 was not powered to compare efficacy in individual subgroups1

NCCNRECOMMENDATION

Brentuximab vedotin (ADCETRIS®) + CHP recommended by NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for first-line PTCL

Category 1 for ALCL and Category 2A for CD30+ histologies other than ALCL3

ALCL = anaplastic large cell lymphoma.

A+CHP demonstrated a significantly higher rate of complete response (CR) vs CHOP1

IRF-Assessed CR Rate (Key Secondary Endpoint)1

  • 83% overall response rate (ORR) in A+CHP arm (95% CI: 78, 88) vs 72% in CHOP arm (95% CI: 66, 78); P = 0.0031
  • Responses based on 2007 International Working Group Criteria at end of treatment1

CI = confidence interval; IRF = independent review facility.

Adverse reactions in the ECHELON-2 trial

  • Most common adverse reactions (≥20%) in combination with CHP1:
  • Anemia (66%)
  • Neutropenia (59%)
  • Peripheral neuropathy (52%)
  • Lymphopenia (51%)
  • Nausea (46%)
  • Diarrhea (38%)
  • Fatigue or asthenia (35%)
  • Mucositis (30%)
  • Constipation (29%)
  • Alopecia (26%)
  • Pyrexia (26%)
  • Vomiting (26%)
  • Serious adverse reactions1:
    • Fatal adverse reactions occurred in 3% of A+CHP patients and 4% of CHOP patients, most often from infection
    • Serious adverse reactions were reported in 38% of A+CHP patients; serious adverse reactions occurring in >2% of A+CHP patients included febrile neutropenia (14%), pneumonia (5%), pyrexia (4%), and sepsis (3%)

ADCETRIS® (brentuximab vedotin) for injection 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.

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

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.
  • 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 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.

Most Common (≥20% in any study) Adverse Reactions

Peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia, stomatitis, lymphopenia, and mucositis.

Drug Interactions

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

Use in Specific Populations

Moderate or severe hepatic impairment or severe renal impairment: MMAE exposure and adverse reactions are increased. Avoid use.

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.

Please see full Prescribing Information, including BOXED WARNING

ADCETRIS® (brentuximab vedotin) for injection 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.

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

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.
  • 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 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.

Most Common (≥20% in any study) Adverse Reactions

Peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia, stomatitis, lymphopenia, and mucositis.

Drug Interactions

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

Use in Specific Populations

Moderate or severe hepatic impairment or severe renal impairment: MMAE exposure and adverse reactions are increased. Avoid use.

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.

Please see full Prescribing Information, including BOXED WARNING

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