FDA Approves Brentuximab Vedotin Plus Chemotherapy for sALCL

The US Food and drug administration (FDA) has approved Seattle Genetics’ brentuximab vedotin (ADCETRIS) in combination with CHP chemotherapy (cyclophosphamide, doxorubicin, prednisone) for the treatment of adults 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.

This treatment stands as the first FDA-approved regimen in frontline peripheral T-cell lymphoma.

In an exclusive interview with Rare Disease Report^®, Robert Chen, MD, highlighted the unique function of the drug. “The reason why the drug is important is because it delivers the treatment specifically to the cancer cells only, and not to normal cells. This is important because it tries to increase the efficacy while limiting the toxicity.”

Data from the phase 3 ECHELON-2 clinical trial, which will be presented at the American Society of Hematology (ASH) 2018 Annual Meeting, served as the basis for the approval. In the multi-center, randomized, double-blind, placebo-controlled phase 3 trial, patients were randomized to be administered either a combination of brentuximab vedotin plus CHP or CHOP, a recognized standard of care for frontline PTCL.

As assessed by a Blinded Independent Central Review facility, the combination treatment with brentuximab vedotin plus CHP was demonstrated to be superior to CHOP for progression free survival (PFS) (BICR; hazard ratio=.71; 95% CI, .54—.93; p-value=.011). In correspondence to the data, the risk of progression, death, or receipt of subsequent anticancer chemotherapy to treat residual or progressive disease was reduced by 29%.

Superior overall survival (OS), a key secondary endpoint, was also demonstrated in the brentuximab vedotin plus CHP arm compared to CHOP (hazard ratio=.66; 95% CI, .46-.95; p-value=.024).

Statistical significance in favor of the brentuximab vedotin plus CHP arm was reflected in all other key secondary endpoints, including PFS in patients with sALCL (hazard ratio=.59; 95% CI, .42- 0.84; p-value=.003), complete remission rate (68% vs 56%; p-value=.007) and objective response rate (83% vs 72%; p-value=.003).

“Brentuximab vedotin plus CHP is the first regimen approved for frontline treatment of peripheral T-cell lymphoma in decades, and the unprecedented speed of this approval by the FDA underscores the unmet clinical need for patients with newly diagnosed CD-30 expressing peripheral T-cell lymphomas,” Nancy Whiting, Pharm.D., senior vice president, Clinical Development and Global Medical Affairs at Seattle Genetics, told Rare Disease Report^®.

A safety profile that was comparable to CHOP and consistent with the established safety profile of brentuximab vedotin in combination with doxorubicin, vinblastine, and dacarbazine (AVD) was demonstrated by brentuximab vedotin plus CHP in the ECHELON-2 trial.

Peripheral neuropathy, nausea, diarrhea, neutropenia, lymphopenia, fatigue, mucositis, constipation, alopecia, pyrexia, vomiting, and anemia included the most common adverse events of any grade that occurred in at least 20% of patients in the brentuximab vedotin plus CHP arm.

Febrile neutropenia, pneumonia, pyrexia, and sepsis included serious adverse reactions occurring in at least 2% of brentuximab vedotin plus CHP-treated patients.

For patients administered brentuximab vedotin plus CHP for previously untreated PTCL, prophylactic growth factors (G-CSF) should be administered starting at cycle 1, according to ECHELON-2 clinical trial results.

“This is the sixth FDA-approved indication for ADCETRIS, which also has approval for adult patients with: (1) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine (AVD), (2) cHL at high risk of relapse or progression as post- autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (3) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (4) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (5) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.”