Clinical Trials Investigate Treatment Options for Precursor Diseases to Multiple Myeloma
The availability of newer agents that have transformed treatment outcomes in multiple myeloma has naturally led to interest in studying these drugs earlier in precursor states, such as monoclonal gammopathy of undetermined significance and smoldering myeloma. Recent evidence suggests that this may be a worthy strategy to pursue, but at present oncologists should not treat precursor states outside of a clinical trial setting, reported C. Ola Landgren, MD, PhD, of Memorial Sloan Kettering Cancer Center, at the recent National Comprehensive Cancer Network 9th Annual Congress on Hematologic Malignancies in New York.
“Many of the newer drugs in multiple myeloma are highly effective and less toxic. Treating earlier with already available drugs looks promising, but we need more well-conducted trials before it is ready for prime time. I urge you to enroll your patients in clinical trials,” he stated.
Treatment Effective in Smoldering Myleoma
The 5-year risk of transforming from smoldering myeloma to multiple myeloma is about 75% in high-risk patients, Dr. Landgren explained. Trials in the 1990s showed no benefit for early treatment, but that was when melphalan was the only drug being studied.
With the advent of newer, more effective therapies, researchers have started to look at the question of early treatment once more. Last year, a Spanish study found that 80% of high-risk patients with smoldering myeloma achieved complete or partial responses after induction with lenalidomide/dexamethasone followed by lenalidomide maintenance for 2 years; this percentage increased to 90% during maintenance until progression. Median progression-free survival was 21 months in patients randomly assigned to observation and was not yet reached for lenalidomide/dexamethasone (P < .001). Two-year survival was 94% for patients treated with lenalidomide/dexamethasone vs 80% in the observation group (P = .03).
This study spurred interest in looking at a three-drug combination for high-risk smoldering myeloma. A small pilot study of carlfilzomib (Kyprolis)/lenalidomide/dexamethasone was undertaken in 12 high-risk patients with smoldering myeloma at the National Cancer Institute, where Dr. Landgren was currently working. After eight full cycles of treatment, “very promising results” were achieved, he said.
All 12 patients had complete response or near complete response at the end of treatment. Toxicity was similar to what has been previously reported with these agents.
“Final results [of the pilot study] will be presented at the 2014 ASH Annual Meeting. I can tell you that the deep responses are even more impressive. We have achieved minimal residual disease status and are doing longitudinal minimal residual disease measurement,” he said.
Understanding the Evolution of Multiple Myeloma
In another study of sequential annual blood samples of 77,000 cancer-free men and women, Dr. Landgren and colleagues reported that 71 developed multiple myeloma. Analysis of the blood samples showed that monoclonal gammopathy of undetermined significance preceded the myeloma in all 71 patients.
“This is a very important observation,” he emphasized.
“Multiple myeloma is massively heterogeneous at diagnosis, and can involve multiple mutations in a subclone and multiple genes in multiple pathways,” Dr. Landgren continued.
Studies of these multiple genes and pathways are attempting to make sense of the evolution of myeloma clones. The interrelationship between the clones and the microenviroment is not clear, and mechanisms of transformation are still unknown.
The current paradigm is not to treat smoldering myeloma, but this is being challenged by new data. However, more data are needed before this question can definitively be answered, he concluded.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
