More than half of patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL, a particularly aggressive type of lymphoma) who received Adcetris (brentuximab vedotin) during a pivotal Phase 2 trial had excellent outcomes in the long run, according to new data.
Of the 58 patients in the trial, 38 (66%) achieved a complete remission, and 16 (42%) of those patients were alive and without signs of disease progression five years after entering the trial.
The positive findings were recently published in the journal Blood, in the study “Five-year results of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma.”
“Historically, sALCL patients who have recurrent or refractory disease have a poor prognosis and outcome with few effective and durable treatment options,” lead author Barbara Pro, MD, of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago, said in a news release.
“Publication of the five-year follow up from the pivotal phase 2 clinical trial results represents a significant milestone for the sALCL community by demonstrating that treatment with single-agent brentuximab vedotin [Adcetris] resulted in high response rates and durable, long-term remissions in conjunction with a manageable safety profile,” Pro said.
Adcetris, jointly developed by Seattle Genetics and Takeda Pharmaceutical, is a type of treatment called an antibody-drug conjugate (ADC). It is composed of a cytotoxic drug attached to a CD30 antibody, making it specific to CD30-positive cells. CD30 is present on Hodgkin’s lymphoma cells and several types of non-Hodgkin’s lymphoma, including sALCL.
Adcetris is being evaluated in more than 70 clinical trials worldwide as the basis of therapy for CD30-expressing lymphomas.
The pivotal, single-arm Phase 2 trial (NCT00866047) supported approvals of Adcetris by the U.S. Food and Drug Administration in 2011 and the European Medicines Agency (EMA) in 2012 for treating relapsed or refractory sALCL.
It included 58 relapsed or refractory sALCL patients to evaluate the efficacy and safety of treatment with Adcetris alone. They were followed up for approximately five years.
The five-year end-of-study results of the Phase 2 trial found that patients who responded to the therapy took a median of 20 months before seeing their disease progress. Also, five years after beginning Adcetris treatment, 60% of patients were still alive, and 39% were progression-free.
Complete remission was seen in 38 patients. Of them, 16 continued to be followed and remained in remission for over five years at the end of the study. Stem cell transplants were conducted in eight of those 16, while the eight others did not need transplants.
Adverse events occurring in more than 20 percent of patients were peripheral neuropathy, nausea, fatigue, fever, diarrhea, rash, constipation and neutropenia, a lack of a type of white blood cell.
A total of 33 patients experienced peripheral neuropathy, which is damage to the nervous system that can affect sensation, movement, gland or organ function, or other aspects of health, depending on the type of nerve affected. The problem was either resolved or improved in 30 (91%) of those affected.
The U.S. Food and Drug Administration has granted Adcetris (brentuximab vedotin) breakthrough therapy designation as a treatment with chemotherapy for some patients with Hodgkin’s lymphoma.
“These data from the pivotal trial in sALCL demonstrate the long-term clinical benefit of Adcetris in the treatment of this disease, with an estimated five-year survival rate of 60 percent and progression-free survival rate of 39 percent,” said Jonathan Drachman, MD, chief medical officer and executive vice president, Research and Development at Seattle Genetics.
“In addition to achieving sustained remissions in the relapsed sALCL treatment setting, these data support the evaluation of Adcetris in earlier lines of therapy, including in the ongoing Phase 3 ECHELON-2 clinical trial in front-line mature T-cell lymphoma, also known as peripheral T-cell lymphoma.”