Multiple Myeloma Advances: Noted Hematologist Envisions Big Changes in Treatment Paradigms

Jesús F. San Miguel, MD, PhD

Clinicians 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 emerging monoclonal antibodies generating promising results in clinical trials and research on risk stratification revealing how to identify which patients should be treated early, according to Jesús F. San Miguel, MD, PhD.

San Miguel delivered the Ham-Wasserman Lecture, entitled “Multiple Myeloma: A Modern Model for Scientific and Clinical Progress,” during the 56th Annual Meeting of the American Society of Hematology (ASH), which convened December 6-9, 2014, at the Moscone Center in San Francisco. He is a professor and administrator at the Clinica Universidad De Navarra, Pamplona, Spain.

During his lecture, San Miguel noted the encouraging clinical trial findings about two new agents in development, daratumumab and elotuzumab, presented during the conference. Clinicians who treat individuals with multiple myeloma and patient advocates have been anticipating research data about these agents for some time now, particularly since the FDA has granted breakthrough therapy status to both agents in multiple myeloma settings.

San Miguel said it has 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.1 But San Miguel said that has turned out not to be the case.

An increased understanding of the genetics behind myeloma is building awareness that treatments must be tailored to the individual, said San Miguel. Identifying and measuring key drivers of the disease holds great promise, he noted, since this will give clinicians information to create combination therapies for more patients. While survival has increased from the abysmal rates of 1 to 3 years from previous eras to 5 to 7 years today, more can be done, he said. San Miguel also reviewed an area where his research team, the Spanish Myeloma Group, made a major contribution in 2013: risk stratification of those patients with precancerous disease who show signs of smoldering myeloma, and methods of identifying those at highest risk of progression so that they can receive early treatment.

He was the senior investigator on a phase III trial in which patients were randomized to receive lenalidomide and dexamethasone or observation, the latter being the usual standard of care for individuals who have an increase of plasma cells in the bone marrow that produce the monoclonal immunoglobulin (IgG), but do not have any myeloma symptoms.2

San Miguel outlined the prognostic factors that allowed the research team to segment out the high-risk group, which included plasma cell bone marrow infiltration, IgG levels, and urinary protein levels.

“You want to give the patient what is needed, and nothing more than is needed,” San Miguel said.

This approach produced improved 3-year survival rates among the high-risk patients identified and treated by the Spanish team during the study; 94% of those who were treated were still alive at 5 years, compared with 80% in the untreated group (HR for death = 0.31; 95% CI, 0.10 to 0.91; P = 0.03).2

While most of his lecture involved cutting-edge science, 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 why we become doctors; this is the reason why we are hematologists,” he concluded.

References

1. Facon T, Dimopoulos MA, Dispenzieri A, et al. Initial phase 3 results of the First (Frontline Investigation Of Lenalidomide + Dexamethasone Versus Standard Thalidomide) Trial (MM-020/IFM 07 01) in newly diagnosed multiple myeloma patients ineligible for stem cell transplantation. Presented at: The 55th ASH Annual Meeting; December 7-10, 2013; New Orleans, LA. Abstract 2.
2. Mateos MV, Hernández MT, Giraldo P, et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med. 2013;369(5):438-447.