Final data from the pivotal phase II trial with brentuximab vedotin (Adcetris®; Seattle Genetics/Takada) in relapsed* or refractory** (r/r) systemic anaplastic large cell lymphoma (sALCL) were published in the journal Blood. The manuscript, which summarizes the five-year, end-of-study results, highlights durable, long-term remissions in sALCL patients treated with brentuximab vedotin monotherapy.
Brentuximab vedotin is an antibody-drug conjugate (ADC) directed to CD30, which is expressed on the surface of Hodgkin lymphoma cells and several types of non-Hodgkin lymphoma, including sALCL. The drug is being evaluated globally as the foundation of therapy for CD30-expressing lymphomas in more than 70 corporate- and investigator-sponsored clinical trials.
Anaplastic large cell lymphoma is a rare type of non-Hodgkin lymphoma, and one of the subtypes of T-cell lymphoma. The disease comprises about one percent of all non-Hodgkin lymphomas and, according to data from the lymphoma research foundation, approximately 16% of all T-cell lymphomas. Anaplastic large cell lymphoma it typically has a less aggressive disease course than systemic disease.
Patients with systemic anaplastic large cell lymphoma or sALCL are generally divided into two main groups. This division depending on whether or not the cells have an abnormal form of a protein, called anaplastic lymphoma kinase or ALK, on their surface. And while both diseases are treated as aggressive or fast-growing, lymphomas, the disease course may be different in patients who have ALK-positive compared with those with ALK-negative 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,” noted Barbara Pro, MD., Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, and lead author of the Blood manuscript.
“Publication of the five-year follow up from the pivotal phase II clinical trial results represents a significant milestone for the sALCL community by demonstrating that treatment with single-agent brentuximab vedotin resulted in high response rates and durable, long-term remissions in conjunction with a manageable safety profile,” she added.
“These data from the pivotal trial in sALCL demonstrate the long-term clinical benefit of brentuximab vedotin in the treatment of this disease, with an estimated five-year survival rate of 60 percent and progression-free survival rate of 39%,” said Jonathan Drachman, M.D., 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 brentuximab vedotin in earlier lines of therapy, including in the ongoing Phase III ECHELON-2 clinical trial in frontline mature T-cell lymphoma, also known as peripheral T-cell lymphoma,” Drachman added.
“With the five-year data of brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma published in Blood in July 2016, these results in sALCL represent the second CD30-expressing malignancy in which five-year data has confirmed clinically significant durable remissions,” said Jesús Gomez-Navarro, M.D., Vice President, Head of Oncology Clinical Research and Development, Takeda.
“These findings further substantiate our goal to establish brentuximab vedotin as the foundation of therapy for CD30-expressing lymphomas,” Navarro further said.
The pivotal, single-arm trial, which supported approvals of brentuximab vedotin by the FDA in 2011 and the European Medicines Agency (EMA) in 2012 for this indication, was conducted in 58 relapsed or refractory sALCL patients to assess the efficacy and safety of single-agent brentuximab vedotin. After a follow-up period of approximately five years, the final results from the pivotal trial include:
The median overall survival was not yet reached and median progression-free survival was estimated at 20 months (95% confidence interval [CI]: 9.4, -). The estimated five-year overall survival and progression-free survival rates were 60% and 39%, respectively.
Of the 58 patients treated, 38 patients (66%) had a complete remission, with the median response duration not reached. For patients who had a complete remission, the median overall survival and progression-free survival were not yet reached.
Sixteen of the 38 patients (42%) who achieved a complete remission continued to be followed and remained in remission for over five years at study closure. Of these patients, eight underwent either autologous or allogenic consolidative stem cell transplants while in remission, and eight received no further therapy.
The most common adverse events of any grade occurring in 20% or more of patients were peripheral neuropathy, nausea, fatigue, pyrexia, diarrhea, rash, constipation and neutropenia. Of the 33 patients who experienced peripheral neuropathy, 30 patients (91%) experienced complete resolution or some improvement of symptoms at last follow-up.
* First progression occurs in the absence of any therapy following successful initial therapy.
** A disease that is progressing despite active treatment.