Early Treatment, Monoclonal Antibodies Discussed in Multiple Myeloma

Those who treat patients with multiple myeloma have witnessed a sea change in the past 15 years. Yet another revolution appears right around the corner, with research on risk-stratification revealing how to identify who should be treated early, and promising results are expected on monoclonal antibodies, said Jesus F. San Miguel, MD, PhD, of the Clinica Universidad De Navarra, Pamplona, Spain.

On Saturday, Dr San Miguel delivered the Han-Wasserman Lecture, “Multiple Myeloma: A Modern Model for Scientific and Clinical Progress,” at the 56th Annual Meeting of the American Society of Hematology (ASH), which is convening December 6-9, 2014, at the Moscone Center in San Francisco.

During his lecture, Dr San Miguel previewed results coming later in the meeting on daratumumab, which binds CD38. Daratumumab and elotuzumab, which received breakthrough status from the FDA in May, have been anticipated by clinicians who treat multiple myeloma and patients for some time now. One of Dr San Miguel’s slides suggested results will show improved survival for 30% to 35% for daratumumab as a single agent, and 64% to 75% of patients in combination with lenalidomide and dexamethasone.

Dr San Miguel it’s become clear that the disease “should not be considered a single entity, but different entities,” and thus, multiple treatment options will exist. For example, he said, many thought there would be no role for melphalan after last year’s ASH meeting in New Orleans, which saw the paradigm-shifting results from Thierry Facon, MD, on lenalidomide and low-dose dexamethasone. But Dr San Miguel said that has turned to not be true.

The talk opened with an overview of the increased understanding of the genetics behind myeloma, which is building awareness that treatments must be tailored to the individual. Identifying and measuring key “drivers” of the disease holds great promise, Dr San Miguel said, as this will give clinicians the information to create combination therapies for more patients. While survival has increased from the abysmal rates of 1 to 3 years of years past to 5 to 7 years today, more can be done, he said.

Dr San Miguel spent considerable time on an area where his group, the Spanish Myeloma Group, made a major contribution in 2013: risk-stratification of those precancerous patients who show signs of “smoldering” myeloma, and identifying those at highest risk of developing the disease for early treatment.

He was the senior investigator of the phase 3 trial published in the New England Journal of Medicine, in which patients were randomized to be treated with lenalidomide and dexamethasone or observation, the latter being the usual standard of care for patients who have an increase of plasma cells in the bone marrow that produce the monoclonal immunoglobulin, but do not have any symptoms. Dr San Miguel outlined the prognostic factors that allowed the research team to segment out the high-risk group. “You want to give the patient what is needed, and nothing more than is needed,” he said.

These results produced improved 3-year survival rates among the high-risk patients identified and treated by the Spanish team; 94% of the treated group was still alive at 5 years, compared with 78% in the untreated group.¹

While most of his talk involved cutting edge science, Dr San Miguel ended on a highly personal note. He thanked his research team in Spain, his family, and especially his wife for many sacrifices. A final slide was a photo of a popular Spanish football team, with faces of his colleagues replacing those of the star players. He thanked the patients and their families, and pharmaceutical leaders who have contributed to the revolution in treating multiple myeloma. “This is the why we become doctors; this is reason why we are hematologists,” he concluded.

Reference

1. Spanish Myeloma Group study a treatment milestone. CenterWatch Newsline. http://www.centerwatch.com/news-online/article/5124/spanish-myeloma-group-study-a-treatment-milestone#sthash.bo7URvWm.dpbs. Published August 5, 2013. Accessed December 5, 2014.