Brentuximab Vedotin Approved in Europe for Frontline ALCL

The European Commission has approved brentuximab vedotin for use in combination with chemotherapy for the frontline treatment of adult patients with systemic anaplastic large cell lymphoma.

Eva Domingo-Domenech, MD

The European Commission has approved of brentuximab vedotin (Adcetris) for use in combination with chemotherapy for the frontline treatment of adult patients with systemic anaplastic large cell lymphoma (sALCL).1

The recommendation, which is specifically for the use of the antibody-drug conjugate in combination with CHP (cyclophosphamide, doxorubicin, prednisone), is based on results from the phase 3 ECHELON-2 trial, in which combining frontline brentuximab vedotin with CHP reduced the risk of disease progression or death by 29% (0.71; 95% CI, 0.54-0.93; P = .011) compared with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), in patients with CD30-positive peripheral T-cell lymphoma (PTCL), including the subtype sALCL.2

An improvement in overall survival outcomes was also observed with the brentuximab vedotin regimen (HR, 0.66; 95% CI, 0.46-0.95; P = .024). Key secondary end points also demonstrated superiority with the brentuximab vedotin combination, including objective response rate (83% vs 72%; P = .003), complete remission rate (CR; 68% vs 56%; P = .007), and progression-free survival (PFS) in patients with sALCL (HR, 0.59; 95% CI, 0.42-0.84; P = .003).

“Clinical outcomes for patients with sALCL have historically been poor; many patients do not achieve long-term survival or remission with the standard of care,” Eva Domingo-Domenech, MD, Institut Català d'Oncologia — Hospitalet, Hospital Duran i Reynals, stated in a press release. “The data from ECHELON-2 showed impressive results for patients treated with Adcetris plus CHP compared to a standard of care, all while maintaining a comparable safety profile. The approval of Adcetris in previously untreated sALCL brings a much needed treatment option to the PTCL community, and I am pleased to be able to offer Adcetris as a first-line option to eligible European patients.”

The double-blind, multicenter, placebo-controlled phase 3 ECHELON-2 trial randomized approximately 450 newly diagnosed patients with CD30-expressing PTCL, also known as mature T-cell lymphoma, to brentuximab vedotin plus CHP or standard CHOP. PFS per independent review was the primary end point, with secondary end points including overall survival, PFS in patients with sALCL; approximately 75% of the overall population), objective response rate, CR rate, and safety.

Adverse events (AEs) across all grades reported in ≥20% of patients receiving the brentuximab vedotin combination were peripheral neuropathy, nausea, diarrhea, neutropenia, lymphopenia, fatigue, mucositis, constipation, alopecia, pyrexia, vomiting, and anemia. Serious AEs occurring in ≥2% of patients in the brentuximab vedotin arm were febrile neutropenia, pneumonia, pyrexia, and sepsis. Based on the study results, the investigators recommend that patients with PTCL being treated with frontline brentuximab vedotin plus CHP should receive G-CSF beginning at cycle 1.

“The European Commission’s decision to approve Adcetris for the first-line treatment of patients with sALCL marks a significant milestone for people diagnosed with this devastating condition,” Teresa Bitetti, president, Global Oncology Business Unit, Takeda, stated in the press release. “Adcetris is the first and only targeted therapy that has been approved in first-line sALCL in several decades. Takeda remains steadfast in our commitment to deliver life changing treatment options to cancer patients worldwide and we are thrilled to have the opportunity to bring this new option to the lymphoma community in Europe.”

Brentuximab vedotin is also approved in Europe for the treatment of adult patients with previously untreated CD30-positive Stage IV Hodgkin lymphoma in combination with doxorubicin, vinblastine and dacarbazine; adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT; adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least 2 prior therapies when ASCT or multi-agent chemotherapy is not a treatment option; adult patients with relapsed or refractory sALCL; and adult patients with CD30-positive cutaneous T-cell lymphoma after at least 1 prior systemic therapy

References

  1. European Commission Approves ADCETRIS® (brentuximab vedotin) for Treatment of Adult Patients with Previously Untreated Systemic Anaplastic Large Cell Lymphoma. Published online May 14, 2020. https://bit.ly/2zEIv3G. Accessed May 14, 2020.
  2. FDA Grants Breakthrough Therapy Designation to ADCETRIS® (Brentuximab Vedotin) for Frontline Peripheral T-Cell Lymphomas. Published online November 15, 2018. https://bit.ly/2zeyd7p. Accessed November 15, 2018.