Brentuximab vedotin (BV), is an antibody drug conjugate that selectively binds to a protein called CD30 on the surface of cells (e.g., Hodgkin lymphoma cells) and delivers a payload of toxin (monomethyl auristatin E) directly to that cell; i.e., a Trojan horse approach to cancer therapy. In 2011, the United States Food and Drug Administration (FDA) approved BV based on a phase II trial in which BV demonstrated an overall response rate (ORR) of 75% and complete response rate (CR) of 34% in patients with Hodgkin lymphoma that had relapsed following autologous hematopoietic cell transplantation (AHCT). Given the promising data, investigators at City of Hope and Weill Cornell Medical College-New York collaborated to evaluate the use of BV prior to AHCT. The standard approach for patients that relapse after first-line therapy includes cytotoxic chemotherapy followed by AHCT. However, this approach can be challenging for some patients and may be associated with some short-term and long-term toxicity. Use of BV prior to AHCT may cause patients some side effects and improve their quality of life prior to AHCT. Preliminary data from this trial were presented yesterday at the 56th Annual Meeting of the American Society of Hematology (ASH).
All patients had biopsy proven Hodgkin lymphoma that had relapsed following therapy with ABVD, BEACOPP, or a combination +/- radiation. Patients were treated with a standard dose of BV intravenously every 3 weeks for a maximum of 4 cycles. Over two-thirds of patients responded, including one third of patients that obtained a CR) and roughly half of the patients were able to proceed to AHCT without receiving additional chemotherapy. Treatments were well tolerated by all patients and no transfusions were required or neutropenic fevers developed.
The results from this trial suggest that BV may be an efficacious option as a first line salvage therapy. It is well tolerated and does not hinder stem cell collection or engraftment. Additional studies will be required to confirm these results. Moreover, this study may lay the groundwork for future studies with promising combinations.