The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of brentuximab vedotin (Adcetris) 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 Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval 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 III 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 endpoints 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).
The European Commission will no review the CHMP recommendation and make its final decision.
"There have been no significant treatment advancements for PTCL over the last few decades. Historically there have been a lack of randomized clinical studies in this setting, making it a challenge to establish an optimal therapy for these patients," Eva Domingo-Domenech, MD, Institut Català d'Oncologia — Hospitalet, Hospital Duran i Reynals, said in a press release. "Outcomes with currently available therapies are often poor, and there is an urgent need for new treatment options. If approved for adult patients with previously untreated sALCL, Adcetris may offer an important option for European patients."
The double-blind, multicenter, placebo-controlled phase III 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 endpoint, with secondary endpoints 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 positive CHMP opinion marks an important step forward for the European sALCL community," Christopher Arendt, head, Oncology Therapeutic Area Unit, Takeda, said in a press release. "ECHELON-2 showed that Adcetris plus CHP demonstrated a significant improvement in progression-free survival and overall survival while maintaining a safety profile comparable to the standard of care of CHOP. We look forward to the European Commission’s review of this positive opinion and hope to bring Adcetris to eligible patients in need."
Brentuximab vedotin is currently 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