Phase II trial suggests therapy should be standard of care for patients facing relapsed or treatment-resistant Hodgkin lymphoma.
Five-year survival data published online in Blood, the Journal of the American Society of Hematology (ASH), suggest that the targeted therapy brentuximab vedotin may have cured some Hodgkin lymphoma patients whose disease has persisted despite receiving previous therapies.
This multinational Phase II study examines brentuximab vedotin (BV) in patients with Hodgkin lymphoma who relapsed after stem cell transplant. The study reports that 13 of 34 (38%) patients who achieved complete remission have remained disease-free for over five years and may be cured. Of those patients, nine received only single-agent BV.
BV is an immunotherapy that targets CD30, a protein on the surface of some Hodgkin lymphoma cells, and delivers a potent dose of chemotherapy to destroy the cell. The therapy is approved by the U.S. Food and Drug Administration for relapsed or treatment-resistant Hodgkin lymphoma, and it is commonly prescribed to patients whose disease has progressed after autologous stem cell transplant, a procedure that replenishes the bone marrow with the patient's own healthy stem cells after therapy. While BV is becoming standard care, this is the first study to observe long-term success in such patients who have exhausted all other treatment options.
"For a patient population that typically only sees an overall survival of one to two years after relapse from autologous stem cell transplantation, the fact that we can report such durable results after five is incredible," said lead author Robert Chen, MD, of City of Hope Cancer Research Center in Duarte, California. Referencing the 15 patients still in remission at the close of this longitudinal study, Dr. Chen said, "Each day that these individuals continue to spend with their loved ones is a testament to the strides our community is making in understanding and beating treatment-resistant lymphomas."
In this study, 102 patients with CD30-positive Hodgkin lymphoma were given one dose (1.8 mg/kg) of BV through outpatient intravenous infusion every three weeks for up to 16 cycles. Prior to beginning this trial, these patients had failed to achieve remission on a median of 3.5 therapies including stem cell transplant, which, prior to BV, was the only potentially curative treatment for those who failed standard chemotherapy. Researchers monitored patients from their initial response (either complete or partial reduction of the tumor) until disease progression or death and continued the study for approximately five years after final treatment.
At five years, 34 of the 102 patients had achieved a complete response (disappearance of their cancer for a period of time), with an estimated 64 percent of patients surviving with or without disease (median five-year overall survival was 40.5 months) and an estimated 52 percent surviving without disease progression. Of these 34 patients, 13 (38%) have remained in remission for five years, and an additional two patients whose disease did not progress after BV went on to achieve remission after receiving allogeneic stem cell transplant (in which healthy stem cells are taken from a donor and administered to the patient). These two patients also remain in remission five years later.
"It is critical to note that nine of the complete response patients have been in remission for over five years after receiving only brentuximab vedotin," said Dr. Chen, "The fact that these patients are doing so well, even five years out, provides a new perspective for prognosis."
Dr. Chen went on to point out that, though 56 of the patients treated in the study experienced mild peripheral neuropathy (an adverse event characterized by tingling in the extremities, commonly reported among those treated with BV), 88 percent reported that symptoms abated over time.
Currently, BV is the subject of several clinical trials. Notable among these are the use of BV prior to autologous stem cell transplant in Hodgkin lymphoma patients, to treat additional CD30-positive lymphomas, and in patients with relapsed or treatment-resistant non-Hodgkin lymphoma.
This trial was supported by Seattle Genetics, Inc., and Millennium Pharmaceuticals, Inc.
Article: Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma, Robert Chen, Ajay K. Gopal, Scott E. Smith, Stephen M. Ansell, Joseph D. Rosenblatt, Kerry J. Savage, Joseph M. Connors, Andreas Engert, Emily K. Larsen, Dirk Huebner, Abraham Fong, Anas Younes, Blood, doi:10.1182/blood-2016-02-699850, published online 18 July 2016.