Approval of brentuximab vedotin for newly diagnosed peripheral T-cell lymphoma (including systemic anaplastic large cell lymphoma)

28 Feb 2019

Despite intensive front-line therapy, peripheral T-cell lymphoma (PTCL) has typically poor clinical outcomes and low complete remission rates.1 Brentuximab vedotin is an antibody-drug conjugate, and with its use in combination with anthracycline-containing regimens shown to be promising in phase 1 studies, the ECHELON-2 trial was carried out, subsequently leading to the approval by the United States Food and Drug Administration (FDA) for use in patients with previously untreated PTCL.1 Additional data were presented at the 2018 American Society of Hematology (ASH) Annual Meeting and Exposition.1,2

There are several subtypes of peripheral T-cell lymphoma (PTCL), including the most common nodal PTCL and anaplastic lymphoma kinase (ALK)-positive or ALK-negative systemic anaplastic large cell lymphoma (sALCL), all which accounts for 10-24% of all non-Hodgkin’s lymphoma cases worldwide.1 PTCL subtypes are typically treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or similar regimens, but often results in poor overall outcomes, including short progression-free survival (PFS), low complete remission rates (CR), and 5-year overall survival (OS) is less than 50% in patients over 40 years old.1

CD30 expression is indicative of sALCL and a hallmark of the diagnosis.1 Brentuximab vedotin is composed of an anti-CD30 monoclonal antibody conjugated to monomethyl auristatin E, a microtubule-disrupting drug.1 ECHELON-2 is a phase 3 trial, aimed to compare the efficacy and safety of brentuximab vedotin plus CHP (CHOP without vincristine) to CHOP for the treatment of previously untreated patients with CD30-positive peripheral T-cell lymphoma, due to the advantageous results of activity and manageable safety profile observed in a phase 1 trial.1 The combination of brentuximab vedotin plus CHP is abbreviated to A+CHP.1

The US FDA granted Breakthrough Therapy designation to brentuximab vedotin in combination with chemotherapy for previously untreated sALCL or other CD30-expressing PTCL on the basis of the data from ECHELON-2.4 Patients who were eligible for ECHELON-2 if they had previously untreated CD30-positive PTCL (≥10% cells) were randomized 1:1 to receive 21-day cycles of 6 to 8 cycles of A+CHP or CHOP.1

The primary outcome of ECHELON-2 was PFS (assessed by an independent review facility), which is defined as until disease progression, subsequent anticancer chemotherapy, death, or study closure; and the secondary outcome measures included measures such as PFS in patients with sALCL, CR rate, OS, and objective response rate (ORR).5

Treatment with A+CHP led to 29% reduction in the risk of PFS (HR=0.71; 95% CI: 0.54-0.93; p=0.0110) and 34% lower risk of death (HR=0.66; 95% CI: 0.46-0.95; p=0.0244), and CR rates and ORR also favored the A+CHP arm compared to the CHOP arm (68% vs. 56% [p=0.007] and 83% vs. 72% [p=0.003] respectively).1,4 Adverse events were shown to be consistent with prior knowledge for both regimens, with the most common being nausea, peripheral neuropathy, neutropenia, and diarrhea.1 There is a black box warning for risk of fatal or life threatening infection of progressive multifocal leukoencephalopathy, and the FDA recommends healthcare providers to monitor patients on life-threatening allergic and infusion reactions, tumor lysis syndrome, neuropathy, and toxicities of the lung or liver.3

The investigators of ECHELON-2 concluded that treatment of A+CHP was associated with higher rates of PFS and OS, supporting its potential to become a new standard of care for patients with CD30-positive PTCL.1 Approval was subsequently granted by the FDA within 2 weeks from application of the data, making brentuximab vedotin the first approved drug for newly diagnosed PTCL including sALCL.3,4



  1. Horwitz S, O’Connor O, Pro B, et al. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2018 [Epub ahead of print].
  2. Stender M. ECHELON-2: Brentuximab Vedotin Plus Chemotherapy in CD30-Positive Peripheral T-Cell Lymphoma. ASCO Post. 2018. (Accessed December 24, 2018 at
  3. Chustecka Z. Approval in 2 weeks via FDA’s New Oncology Drugs Review. Medscape. 2018. (Accessed December 24, 2018, at
  4. FDA approves brentixumab vedotin for previously untreated sALCL and CD30-expressing PTCL. FDA. 2018. (Accessed December 24, 2018, at
  5. ECHELON-2: A Comparison of Brentuximab Vedotin and CHP with Standard-of-care CHOP in the Treatment of Patients with CD30-positive Mature T-cell Lymphomas (ECHELON-2). (Accessed December 24, 2018, at