ASH Clinical News Focus on Rare Diseases

MEETING COVERAGE Examining Mogamulizumab for T-Cell Leukemia and Lymphoma Patients with adult T-cell leukemia and lymphoma (ATLL), a rare T-cell malignancy caused by the human T lymphotropic virus type 1 (HTLV-1), have limited therapeutic options. With no established standards of care, most patients are treated with the same cytotoxic therapies used in other T-cell malignancies. Results from a randomized phase II trial presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting suggests that the novel anti-CCR4 antibody mogamulizumab induces better response rates than currently available therapies. ASH Clinical News spoke with Adrienne A. Phillips, MD, MPH, who presented the results, about mogamulizumab and the future of immune-based therapies for ATLL. What is ATLL, and why are you studying mogamulizumab? ATLL is a T-cell neoplasm that we don’t see commonly in the United States; it’s more common in Japan, Latin America, and the Caribbean. We know that ATLL is caused by the HTLV-1 virus, but we only see a few cases. The Surveillance, Epidemiology, and End Results database estimates that there are about 120 cases per year in the United States – primarily in centers that treat immigrants who come from regions where ATLL is endemic. In Japan, mogamulizumab has been approved for the treatment of ATLL; outside of Japan, ATLL patients have limited treatment options. With the current trial, which is the largest study in relapsed/refractory ATLL, we enrolled 71 patients from sites in the United Kingdom, France, Brazil, Peru, and Martinique. We had to open the trial at 22 sites around the world because the disease is just that uncommon. It was a herculean effort, but we did it. Personally, this trial taught me the importance of working together with multiple centers. I tried to open a single-center study to treat patients with ATLL when I was just out of fellowship, but I had to close it because I couldn’t accrue enough patients. So, this was a great accomplishment for ATLL patients. Because ATLL is so rare, there aren’t any real guidelines mandating treatment – is the treatment choice up to the physician in most situations? It is. In this trial, patients were randomized to receive mogamulizumab or an investigators’ choice. We polled the lead investigators to assess what their choices might be, because we don’t have a standard therapy for this disease. Since there isn’t a standard therapy for ATLL, they have been using drugs that are active in other T-cell malignancies, such as methotrexate, dihydroxyacetone phosphate, and gemcitabine plus oxaliplatin. What did you find in this study? There were two interesting observations. First, mogamulizumab was effective for patients with ATLL, producing an overall response rate of about 34 percent, as assessed by the investigator. 24 Focus on Rare Diseases Adrienne A. Phillips, MD, MPH Second, when we looked at the response rate to investigators’ chosen therapies, the response rate was zero; there was little therapeutic benefit with these cytotoxic regimens. This showed that our currently available options are really ineffective. We need to continue to investigate novel agents for patients with this disease. What are the next steps for mogamulizumab? The sponsoring pharmaceutical company is in talks with the U.S. FDA to safely advance this drug forward and make it available for ATLL patients outside of Japan. Although the 34 percent response rate is encouraging, it’s not a “home run,” so we’re still looking for other therapies and combinations that will be even more effective for ATLL patients. We studied mogamulizumab as a single agent; perhaps in future trials, we will look at combining it with other agents. The study results also confirmed that immunotherapy is a promising area of research for ATLL patients. It might be the future of this disease. ● Adrienne A. Phillips, MD, MPH, is assistant professor of medicine at Weill Cornell Medical College and assistant attending physician at the New York-Presbyterian Hospital in New York. Reference Phillips AA, Fields P, Hermine O, et al. A prospective, multicenter, randomized study of anti-CCR4 monoclonal antibody mogamulizumab (moga) vs investigator's choice (IC) in the treatment of patients (pts) with relapsed/ refractory (R/R) adult T-cell leukemia-lymphoma (ATL). Abstract #7501. Presented at the 2016 American Society of Clinical Oncology Annual Meeting, June 6, 2016; Chicago, IL.

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