Is Early Intervention for Smoldering Multiple Myeloma Beneficial?

The majority of patients with high-risk smoldering multiple myeloma (SMM) will eventually progress to multiple myeloma (MM) as predicted by their baseline risk assessment, according to clinical trial data that supports early intervention in high-risk patients.

The study also found that clinically significant end-organ damage may not be preventable, and that progression to MM is not always detected by routine interval surveillance testing.

Led by Nadine Abdallah, MD, of the Mayo Clinic in Rochester, Minnesota, the study aimed to describe the myeloma-defining events (MDEs) and clinical presentations leading to MM diagnosis among SMM patients. Dr. Abdallah and colleagues conducted the study because despite clinical trial data suggesting benefit from early intervention, most patients with SMM are observed.

The study included 406 patients seen at the Mayo Clinic between 2013 and 2022. Twenty-four percent of patients met MM criteria based on marrow plasmacytosis (≥60%) or free light chain ratio (>100), while 45% had clinically significant MDEs (hypercalcemia, renal insufficiency, or bone lesions).

Of 90 patients with high-risk SMM, 21% received early intervention and 79% were observed. At a median follow-up of 3.9 years, two patients (11%) who received early treatment progressed to MM, compared with 51 (72%) patients who were observed.

The MDEs for high-risk patients included bone lesions (37%), anemia (35%), hypercalcemia (8%), and renal failure (6%). Among high-risk patients who were observed and progressed by last-follow-up, the presentations leading to MM diagnosis included surveillance labs or surveillance imaging (44%), work-up due to laboratory changes (14%), bone pain (19%), work-up for an unrelated symptom (2%), and hospitalization due to MM complications or symptoms (4%).

Of 226 nonhigh-risk patients, 35 (15%) received treatment for SMM after a median of four months after diagnosis, and 191 (85%) were observed. Three patients (9%) who received treatment progressed, compared with 59 (31%) of patients who were observed.

The MDEs for nonhigh-risk patients included bone lesions (51%), anemia (36%), hypercalcemia (7%), renal insufficiency (8%), and bone marrow plasma cells or free light chain ratio criteria (14%). For nonhigh-risk patients, the presentations leading to MM diagnosis included surveillance labs or surveillance imaging (32%), work-up due to laboratory changes (17%), bone pain (20%), work-up for unrelated medical condition/symptom (7%), unknown presentation (14%), and hospitalization due to MM complications or symptoms (10%).

About 50% of patients who progressed to MM had clinically significant end-organ damage, including one patient who progressed to end-stage renal disease.

According to Dr. Abdallah and colleagues, early intervention in patients with high-risk SMM is justified by the morbidity associated with progression to MM reported in this study; the benefit in delaying progression reported in prior trials such as the QuiRedex study and the ECOG-ACRIN study; and the lack of evidence for emergence of resistant clones.

“These findings may provide support for early intervention in high-risk patients,” the researchers concluded. “Efforts to further refine the current risk stratification systems will better delineate the subset of patients who would benefit from early intervention in the future.”

Reference

Abdallah NH, Lakshman A, Kumar SK, et al. Mode of progression in smoldering multiple myeloma: a study of 406 patients. Blood Cancer J. 2024. doi.org/10.1038/s41408-024-00980-5