Combination Therapy Followed by Brentuximab Vedotin Consolidation Demonstrated Safety, Activity Among Patients With CD30-Expressing Peripheral T-Cell Lymphomas

According to results from a phase 2 trial, treatment with cyclophosphamide, doxorubicin, prednisone, brentuximab vedotin, and etoposide (CHEP–BV), with or without autologous hematopoietic stem-cell transplantation (autoHSCT), followed by brentuximab vedotin consolidation therapy demonstrated safety and activity among patients with mostly CD30-expressing peripheral T-cell lymphomas.

“Incorporation of brentuximab vedotin into initial therapy for people with CD30+ peripheral T-cell lymphomas prolonged progression-free survival (PFS), but there is room for improvement, especially for people with non-anaplastic large-cell lymphoma subtypes,” stated first study author Alex Herrera, MD, City of Hope, Duarte, California, and colleagues.

Across 5 academic centers in the United States and Canada, participants were recruited and enrolled between December 4, 2017, and June 14, 2021, and followed up until August 25^th, 2023. For this study, investigators included 48 eligible adults aged 18 years or older with newly diagnosed, untreated CD30+ peripheral T-cell lymphomas, an Eastern Cooperative Oncology Group (ECOG) score of 0 to 2, and adequate organ function. These patients were able to receive 6 planned cycles of CHEP–BV (1.8 mg/kg brentuximab vedotin intravenously on day 1, cyclophosphamide 750 mg/m² intravenously on day 1, doxorubicin 50 mg/m² intravenously on day 1, etoposide 100 mg/m² daily intravenously on days 1 to 3, and prednisone 100 mg daily orally on days 1 to 5) with prophylactic granulocyte colony-stimulating factors (G-CSF).

Patients who responded to this treatment regimen could receive brentuximab vedotin consolidation for up to 10 additional cycles either after autologous HSCT or directly following CHEP–BV. Researchers noted the primary end points were unacceptable toxicity during a 3-plus-3 safety lead-in among participants who received study treatment and completed the safety evaluation period and the complete response (CR) rate after CHEP–BV induction therapy in participants who received study treatment and had response evaluation.

Trial results demonstrated that all 48 participants were evaluable for toxicity, and 47 were evaluable for response (1 study participant experienced mortality from COVID-19 complications before response assessment). During the safety lead-in, 1 of 6 patients had an unacceptable toxicity (platelet count <10,000/mm³ in a participant with extensive bone marrow involvement), and the proposed phase 2 dose of 1.8 mg/kg brentuximab vedotin in CHEP–BV was confirmed. Furthermore, at the completion of CHEP–BV, 37 of 47 participants had CR, highlighting a CR rate of 79% (95% confidence interval [CI], 64 to 89).

The adverse event safety profile included CHEP–BV-related toxicities of grade 3 or higher of neutropenia (14 [29%] of 48), leukopenia (11 [23%]), anemia (10 [21%]), febrile neutropenia (10 [21%]), lymphopenia (9 [19%]), and thrombocytopenia (9 [19%]). There were no treatment-related deaths.

“In patients with mostly CD30-expressing peripheral T-cell lymphomas other than non-anaplastic large-cell lymphoma, CHEP–BV (with or without autologous HSCT) followed by brentuximab vedotin consolidation was safe and active,” concluded Dr Herrera and colleagues.

Source:

Herrera H, Zain J, Savage K, et al. Brentuximab vedotin plus cyclophosphamide, doxorubicin, etoposide, and prednisone followed by brentuximab vedotin consolidation in CD30-positive peripheral T-cell lymphomas: A multicenter, single-arm, phase 2 study. Published online July 24, 2024. doi: 10.1016/S2352-3026(24)00171-6