The anti-CCR4 antibody mogamulizumab showed promising response rates compared to investigator’s choice in a randomized phase II trial of relapsed/refractory adult T-cell leukemia/lymphoma (ATL). The study was presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held earlier this month in Chicago.
ATL is a rare malignancy of T cells infected with human T lymphotropic virus type 1. The virus is endemic to various regions of the world, including Japan, parts of South America, and Africa, among others.
“The majority of patients infected with this virus never manifest any symptoms, however the cumulative lifetime risk of developing ATL is approximately 2% to 7%,” said Adrienne A. Phillips, MD, MPH, of NewYork–Presbyterian/Weill Cornell Medical College, who presented the study. ATL has the worst prognosis of the T cell lymphomas.
Though a variety of therapies have been tried in this malignancy, there is no standard first-line treatment, and outside of Japan there are no approved therapies; Phillips called this a high unmet clinical need. CC chemokine receptor 4 (CCR4) is overexpressed on the surface of cells in T-cell malignancies, and expression of CCR4 in ATL is about 90%. Mogamulizumab targets CCR4, and is approved in Japan for ATL and several other malignancies.
The new study included 71 patients, representing the largest ever randomized trial in ATL. All patients had relapsed/refractory disease, and were at least 18 years of age. Forty-seven were treated with mogamulizumab, and 24 were treated with investigator’s choice, which included pralatrexate, DHAP, or gemcitabine/oxaliplatin. There were some baseline demographic differences: those receiving mogamulizumab were more likely to be over the age of 65 years, have an ECOG performance status of 2, and have bone marrow involvement.
There were zero responses in the investigator’s choice group, compared with 16 in the mogamulizumab group (34%); 7 of those responses were confirmed, meaning the response was maintained at successive evaluations over about 8 weeks. On independent review, there were two responses in the investigator’s choice group, though neither was confirmed, and 13 in the mogamulizumab group, five of which were confirmed.
After progression, the investigator’s choice patients could cross over to receive mogamulizumab. Of 18 patients who did so, three had a response (17%), with one confirmed.
The most common treatment-emergent adverse events with mogamulizumab included infections (51.1%), infusion-related reactions (46.8%), and drug eruptions (19.1%).
The discussant for the session, Sonali M. Smith, MD, of the University of Chicago, said “there is a positive signal here. Not a homerun, but certainly, for a patient population that has never had any options, this is really exciting.”