Smoldering Multiple Myeloma: An Overview for Newly Diagnosed Patients

Receiving a diagnosis of smoldering multiple myeloma (SMM) can feel like standing in a medical waiting room. It is a complex, intermediary stage of plasma cell disorders that requires a nuanced approach to care.

The following guide is designed to help you navigate your upcoming appointments and facilitate a proactive dialogue with your oncology team.

Overview: The Asymptomatic Bridge

Smoldering multiple myeloma is a precancerous condition characterized by the presence of abnormal plasma cells in the bone marrow and elevated levels of monoclonal protein (M-protein) in the blood.

Unlike active multiple myeloma, SMM is asymptomatic. This means you likely do not have the "CRAB" symptoms typically associated with end-organ damage:

• Calcium elevation
• Renal (kidney) insufficiency
• Anemia
• Bone lesions

Think of SMM as a bridge between monoclonal gammopathy of undetermined significance (MGUS) and active, symptomatic disease. While some patients may not progress for many years, others are at a higher risk of the condition evolving into full-blown myeloma.

Diagnosis and Risk Stratification

Doctors diagnose SMM through a combination of blood, urine, and bone marrow tests.

Once diagnosed, your oncologist will use risk stratification (such as the "2/20/20" rule) to determine the likelihood of progression. This involves looking at the M-protein levels, the free light chain ratio and the percentage of plasma cells in the marrow.

Treatment Options: Watchful Waiting versus Intervention

For decades, the standard of care for SMM was "Watch and Wait." Today, the philosophy is shifting toward "Observation versus Early Intervention," depending on your risk profile.

• Observation: For low-risk patients, doctors perform regular blood work and imaging every three to six months to monitor for changes.
• Clinical Trials: Many experts recommend high-risk SMM patients enroll in clinical trials. These studies investigate whether early treatment with immunotherapy or chemotherapy can delay or prevent progression.
• Active Therapy: In certain high-risk cases, treatments used for active myeloma — such as Revlimid (lenalidomide)—may be prescribed to slow the disease.

In recent news, the U.S. Food and Drug Administration (FDA) announced that it had approved Darzalex Faspro (daratumumab and hyaluronidase-fihj) for the treatment of adults with high-risk smoldering multiple myeloma.

A poster presented at the 2025 Society of Hematologic Oncology Annual Meeting showed that with subcutaneous Darzalex Faspro, with a median follow-up of 65.2 months and the median progression-free survival not reached with Darzalex Faspro versus 41.5 months with monitoring, there was a 51% reduction in the risk of progressive disease or death.

“Darzalex Faspro demonstrated a favorable safety profile, with a low rate (5.7%) of treatment discontinuation due to treatment-emergent side effects. Patients maintained their health-related quality of life during Darzalex Faspro treatment compared with active monitoring,” lead study author, Dr. Meletios Athanasios Dimopoulos, professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine in Greece, wrote in the poster with coauthors.

“Results from the phase 3 AQUILA study strongly support early intervention with subcutaneous Darzalex Faspro monotherapy for a fixed duration in patients with high-risk smoldering multiple myeloma, representing an opportunity to delay or avoid end-organ damage and progression to multiple myeloma although preserving quality of life and extending survival.”

Potential Side Effects

If you and your doctor decide on early intervention, it is important to understand the side effects of common myeloma therapies:

Immunomodulatory drugs: Fatigue, skin rash, diarrhea, and increased risk of blood clots.

Proteasome inhibitors: Peripheral neuropathy (numbness/tingling in hands/feet) and shingles.

Corticosteroids: Insomnia, mood swings, increased appetite and elevated blood sugar.

Even in "Watchful Waiting," the primary side effect is often psychological stress or "scanxiety." Maintaining open communication with a mental health professional or support group is highly recommended.

Conclusion

A diagnosis of smoldering multiple myeloma does not mean an immediate transition to aggressive chemotherapy. It does, however, mean you are now the CEO of your own health. By monitoring the "CRAB" markers and understanding your risk category, you can make informed decisions about when — or if — to start treatment.

Questions for Your Oncologist

1. "Am I considered low, intermediate, or high-risk for progression?"
2. "What specific markers in my blood work are we watching most closely?"
3. "Are there clinical trials available that might benefit someone with my specific markers?"

Reference

1. “FDA Approves Darzalex Faspro in High-Risk Smoldering Multiple Myeloma,” CURE; https://www.curetoday.com/view/fda-approves-darzalex-faspro-in-high-risk-smoldering-multiple-myeloma

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI and reviewed by a human editor.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.