Adults with
Previously untreated sALCL or other CD30-expressing PTCLs
Efficacy
Model portrayals.
Available on this page:
Progression-free Survival: 3 Years
An event was defined as the time from randomization to progression, death due to any cause, or receipt of subsequent anticancer therapy to treat residual or progressive disease.1
A+CHP = ADCETRIS + cyclophosphamide, doxorubicin, and prednisone; CHOP = cyclophosphamide, doxorubicin, vincristine, prednisone; CHP = cyclophosphamide, doxorubicin, and prednisone; CI = confidence interval; HR = hazard ratio; IRF = independent review facility; NE = not estimable; PFS = progression-free survival.
Progression-free Survival: 5 Years
The 5-year analysis of ECHELON-2 for PFS per INV was a post-hoc exploratory analysis. This analysis is descriptive in nature, and offers supportive, but not conclusive, clinical information only. This analysis was not statistically powered to determine differences between treatment arms.
- Median follow-up: 47.6 months2
- Estimated PFS rates at 5 years per INV2:
- A+CHP: 51.4% (95% CI: 42.8, 59.4)
- CHOP: 43.0% (95% CI: 35.8, 50.0)
INV = investigator; ITT = intent-to-treat.
Overall Survival: 3 Years
A+CHP showed improved OS vs CHOP1
HR: 0.66 (95% CI: 0.46, 0.95); P = 0.024
- Median os was not reached in either arm2
- Median follow-up: 41.9 months for a+chp and 42.2 months for chop1
A+CHP = ADCETRIS + cyclophosphamide, doxorubicin, and prednisone; CHOP = cyclophosphamide, doxorubicin, vincristine, prednisone; CHP = cyclophosphamide, doxorubicin, and prednisone; CI = confidence interval; HR = hazard ratio; OS = overall survival.
Overall Survival: 5 Years
OS analysis at 5 years of follow-up
The 5-year follow-up analysis of ECHELON-2 was a post-hoc exploratory analysis. This analysis is descriptive in nature, and offers supportive, but not conclusive, clinical information only. This analysis was not statistically powered to determine differences between treatment arms.
- Median follow-up: 66.8 months2
- Median OS not reached in either arm2
Peer perspective on the overall survival advantage
“It was really interesting to see the data and the positive results across different subtypes of PTCL, progression-free survival benefit, and even overall survival benefit.”
Dr Francine Foss, hematologist-oncologist
Complete Response
A+CHP demonstrated a significantly higher rate of complete response (CR) vs CHOP
- 83% 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
ORR = overall response rate.
Trial Design
Explore ECHELON-2 Trial Design
Large, multicenter, phase 3, randomized, double-blind, double-dummy, actively controlled trial
(N = 452)1,3
Dosage in ECHELON-2
- A+CHP (ADCETRIS 1.8 mg/kg, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2 intravenously on Day 1 + prednisone 100 mg orally on Days 1-5)1,3
- CHOP (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2 [max 2 mg] intravenously on Day 1 + prednisone 100 mg orally on Days 1-5)1,3
- In the A+CHP arm, 6 cycles were planned in 81% of patients. 70% of A+CHP patients received 6 cycles of ADCETRIS and 18% received 8 cycles. G-CSF primary prophylaxis was administered to 34% of A+CHP patients and 27% of CHOP patients1
Study endpoints in ECHELON-2
- The primary endpoint was PFS per IRF; an event was defined as progression, death from any cause, or receipt of subsequent anticancer therapy to treat residual or progressive disease1
-
Key secondary endpoints included1:
- Overall survival
- CR rate
- Overall response rate
- PFS for sALCL subgroup
Primary inclusion criteria
- Adults (≥18 years) with previously untreated CD30-expressing PTCLs1
- CD30 expression in ≥10% of neoplastic cells1
- Trial excluded patients with Grade ≥2 peripheral neuropathy1
Baseline patient characteristics
- Generally well balanced between treatment arms3
- Overall median age was 58 years (range, 18-85)1
- Most patients had Stage III or IV disease (81%) and a baseline IPI of 2 or 3 (63%)1
- Subtypes enrolled1:
- sALCL (70%; 48% ALK– and 22% ALK+)
- PTCL-NOS (16%)
- AITL (12%)
- ATLL (2%)
- EATL (<1%)
- 75% (±5%) enrollment of patients with sALCL was targeted to appropriately evaluate PFS in sALCL and confirm positive benefit/risk balance3
Computed tomography (CT) scans were required at 9, 12, 15, 18, 21, and 24 months after treatment initiation, and every 6 months thereafter until progression, death, or analysis of the primary endpoint.3
AITL = angioimmunoblastic T-cell lymphoma; ALK = anaplastic lymphoma kinase; ATLL = adult T-cell leukemia/lymphoma; CR = complete response; EATL = enteropathy-associated T-cell lymphoma; EMA = European Medicines Agency; G-CSF = granulocyte-colony stimulating factor; IPI = International Prognostic Index; OS = overall survival; PTCL = peripheral T-cell lymphoma; PTCL-NOS = peripheral T-cell lymphoma not otherwise specified; sALCL = systemic anaplastic large cell lymphoma.
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. Horwitz S, O'Connor OA, Pro B, et al. The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma. Ann Oncol. 2022;33:288-298.
- 3. Horwitz S, O’Connor OA, Pro B, et al; for the ECHELON-2 Study Group. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019;393:229-240.
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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