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From Smolder to Strategy: Optimizing Early Treatment Decisions in High-Risk SMM and NDMM

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This activity is available for 1.00 CME/CE credit(s).

Released: October 22, 2026

Expiration: April 21, 2027

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Step 1 of 5

1 Pre Assessment 2 Text Module 3 Post Assessment 4 Evaluation 5 Credit

The care of patients diagnosed with high-risk smoldering multiple myeloma (MM) or newly diagnosed active MM continues to evolve with the rapid release of new clinical evidence. This module features an expert’s evidence-based perspectives on the need for accurate risk stratification, evidence for early intervention, and how to decide between treatment and observation in an individualized manner for patients with high-risk smoldering MM, as well as the optimal approaches for the selection of frontline therapy for patients who are newly diagnosed with active MM requiring treatment. The module also includes a synthesized review of the evolving treatment landscape, recommended guidelines, and ongoing clinical trials for patients with high-risk smoldering MM and those with newly diagnosed active MM.

Natalie S. Callander
Natalie S. Callander, MD
Therapies for High Risk SMM and NDMM

Pre Assessment

Assess your current knowledge and clinical approach before beginning your text module.
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1.

How many people with multiple myeloma (MM) do you provide care for in a typical month?​

2.

For those who practice in academic or community settings, please indicate your practice setting:

3.

A 58-year-old woman with no previous medical history is referred to hematology because of elevated mean corpuscular volume and leukopenia. Her laboratory results show white blood cell count 4.3 x 10⁹/L, hemoglobin 14.9 g/dL, platelets 252 x 10⁹/L, serum protein 7.5 g/dL, albumin 4.8 g/dL, creatinine 0.9 mg/dL, IgG 1436 mg/dL, IgA 42 mg/dL, IgM 49 mg/dL, M-spike 0.9 g/dL, and free light chain ratio 41.15. Serum immunofixation revealed IgG kappa. Workup using 24-hour urine showed 90 mg protein and no M-spike, and urine immunofixation electrophoresis was positive for kappa light chains. Bone marrow biopsy showed 40% kappa-restricted plasma cells. Fluorescence in situ hybridization (FISH) analysis showed 1q+, del(13q). PET/CT and MRI scans showed no bone lesions.

 Using the International Myeloma Working Group (IMWG) 2/20/20 refined risk stratification model, would you consider treatment for this patient?

4.

  As of October 2026, which of the following treatments is approved by the FDA for patients with high-risk SMM?

5.

A 77-year-old man with newly diagnosed symptomatic MM presents with fatigue and bone pain. Laboratory findings include hemoglobin 9.8 g/dL, creatinine 1.1 mg/dL, calcium 11.9 mg/dL, M protein 3.2 g/dL, and FLC ratio 45. Bone marrow evaluation shows 40% clonal plasma cells, and imaging reveals multiple lytic lesions. Cytogenetics demonstrates high-risk disease with t(4;14) and +1q. Comorbidities include hypertension that is well controlled, and he has an Eastern Cooperative Oncology Group performance status of 1. He is not eligible for autologous stem cell transplant (ASCT) because of his age and patient preference, but he is otherwise fit and not frail.

Which frontline regimen would you recommend for this patient?

6.

Which emerging MRD-guided treatment strategy is being investigated in the ongoing randomized phase III DETERMINATION 2 trial for transplant-eligible patients with newly diagnosed MM?

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