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Asymptomatic Plasma Cell Neoplasms (Smoldering Multiple Myeloma)
Source: Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)–Health Professional Version, National Cancer Institute.
Source updated: April 25, 2025 · Captured 2026-09-09.
Selected source text with whitespace normalised. This Triangle page is not an NCI PDQ summary.
Context: Treatment Option Overview for Plasma Cell Neoplasms
Asymptomatic patients with multiple myeloma who have no lytic bone lesions and normal renal function may be initially observed safely outside the context of a clinical trial.[1,4,5] Increasing anemia is the most reliable indicator of progression.[5] The following criteria represent the new definition for smoldering myeloma:[3]
Serum monoclonal protein immunoglobulin (Ig) G or IgA of at least 30 g/L or urinary monoclonal protein of at least 500 mg per 24 hours.
Clonal bone marrow plasma cells 10% to 60% (>60% represents overt myeloma).
Absence of amyloidosis or myeloma-defining events as follows:
Absence of amyloidosis or myeloma-defining events as follows:
Hypercalcemia greater than 1 mg/dL higher than reference range.
Absence of amyloidosis or myeloma-defining events as follows:
Creatinine greater than 2 mg/dL or creatinine clearance less than 40 mL/min.
Absence of amyloidosis or myeloma-defining events as follows:
Anemia with hemoglobin less than 10.0 g/dL.
Absence of amyloidosis or myeloma-defining events as follows:
Bone lesions (one or more) on skeletal radiography, computed tomography (CT) or positron emission tomography (PET)-CT.
Absence of amyloidosis or myeloma-defining events as follows:
Clonal plasma cell percentage in marrow at 60% or more.
Absence of amyloidosis or myeloma-defining events as follows:
Involved:uninvolved serum free light chain (FLC) ratio of 100 or more.
Absence of amyloidosis or myeloma-defining events as follows:
More than one focal lesion of at least 5 mm on magnetic resonance imaging (MRI) of the spine.
The International Myeloma Working Group (IMWG) 2/20/20 rule measures four adverse risk factors for patients with smoldering myeloma. The presence of three or four of the following adverse factors predicts a greater than 50% chance of progression to myeloma within 2 years:[6]
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Serum monoclonal (or myeloma) protein (M protein) greater than 2 g/dL.
Involved:uninvolved serum FLC ratio of more than 20.
Bone marrow plasma cell infiltration of more than 20%.
t(4;14), t(14;16), 1q gain, or del13q/monosomy 13 chromosomal abnormality.
Clinical trials evaluating smoldering myeloma need to exclude patients at high risk of progression to myeloma because those patients should consider induction therapy for symptomatic patients. For more information, see the Symptomatic Plasma Cell Neoplasms section.
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In a prospective randomized trial of 390 patients with smoldering myeloma, patients were eligible if the marrow plasmacytosis was 10% to 49% and one of the following criteria was met: These patients received daratumumab (the anti-CD38 monoclonal antibody) or no therapy.[7]Summary: This trial did not show a significant improvement in OS or quality of life. However, the significant and clinically relevant delay in progression may particularly benefit older, less fit patients with myeloma. Early use of daratumumab did not result in a shortened OS after the subsequent initiation of full-dose induction therapy.
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In a prospective randomized trial of 390 patients with smoldering myeloma, patients were eligible if the marrow plasmacytosis was 10% to 49% and one of the following criteria was met: These patients received daratumumab (the anti-CD38 monoclonal antibody) or no therapy.[7]Summary: This trial did not show a significant improvement in OS or quality of life. However, the significant and clinically relevant delay in progression may particularly benefit older, less fit patients with myeloma. Early use of daratumumab did not result in a shortened OS after the subsequent initiation of full-dose induction therapy.
M protein of at least 3 g/dL.
In a prospective randomized trial of 390 patients with smoldering myeloma, patients were eligible if the marrow plasmacytosis was 10% to 49% and one of the following criteria was met: These patients received daratumumab (the anti-CD38 monoclonal antibody) or no therapy.[7]Summary: This trial did not show a significant improvement in OS or quality of life. However, the significant and clinically relevant delay in progression may particularly benefit older, less fit patients with myeloma. Early use of daratumumab did not result in a shortened OS after the subsequent initiation of full-dose induction therapy.
Immunoparesis of two Ig classes.
In a prospective randomized trial of 390 patients with smoldering myeloma, patients were eligible if the marrow plasmacytosis was 10% to 49% and one of the following criteria was met: These patients received daratumumab (the anti-CD38 monoclonal antibody) or no therapy.[7]Summary: This trial did not show a significant improvement in OS or quality of life. However, the significant and clinically relevant delay in progression may particularly benefit older, less fit patients with myeloma. Early use of daratumumab did not result in a shortened OS after the subsequent initiation of full-dose induction therapy.
Involved:uninvolved serum FLC ratio of 8 to 99.
In a prospective randomized trial of 390 patients with smoldering myeloma, patients were eligible if the marrow plasmacytosis was 10% to 49% and one of the following criteria was met: These patients received daratumumab (the anti-CD38 monoclonal antibody) or no therapy.[7]Summary: This trial did not show a significant improvement in OS or quality of life. However, the significant and clinically relevant delay in progression may particularly benefit older, less fit patients with myeloma. Early use of daratumumab did not result in a shortened OS after the subsequent initiation of full-dose induction therapy.
IgA monoclonal protein.
In a prospective randomized trial of 390 patients with smoldering myeloma, patients were eligible if the marrow plasmacytosis was 10% to 49% and one of the following criteria was met: These patients received daratumumab (the anti-CD38 monoclonal antibody) or no therapy.[7]Summary: This trial did not show a significant improvement in OS or quality of life. However, the significant and clinically relevant delay in progression may particularly benefit older, less fit patients with myeloma. Early use of daratumumab did not result in a shortened OS after the subsequent initiation of full-dose induction therapy.
Marrow plasmacytosis of 50% to 59%.
In a prospective randomized trial of 390 patients with smoldering myeloma, patients were eligible if the marrow plasmacytosis was 10% to 49% and one of the following criteria was met: These patients received daratumumab (the anti-CD38 monoclonal antibody) or no therapy.[7]Summary: This trial did not show a significant improvement in OS or quality of life. However, the significant and clinically relevant delay in progression may particularly benefit older, less fit patients with myeloma. Early use of daratumumab did not result in a shortened OS after the subsequent initiation of full-dose induction therapy.
With a median follow-up of 65.2 months, the 5-year progression-free survival rate was 63.1% for patients in the daratumumab arm and 40.8% for patients in the watchful waiting arm (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.36–0.67; P < .0001).[7][Level of evidence B1]
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In a prospective randomized trial of 390 patients with smoldering myeloma, patients were eligible if the marrow plasmacytosis was 10% to 49% and one of the following criteria was met: These patients received daratumumab (the anti-CD38 monoclonal antibody) or no therapy.[7]Summary: This trial did not show a significant improvement in OS or quality of life. However, the significant and clinically relevant delay in progression may particularly benefit older, less fit patients with myeloma. Early use of daratumumab did not result in a shortened OS after the subsequent initiation of full-dose induction therapy.
The median time to progression was 44.1 months for patients in the daratumumab arm and 17.8 months for patients in the watchful waiting arm (HR, 0.51; 95% CI, 0.40–0.66; P < .0001).
In a prospective randomized trial of 390 patients with smoldering myeloma, patients were eligible if the marrow plasmacytosis was 10% to 49% and one of the following criteria was met: These patients received daratumumab (the anti-CD38 monoclonal antibody) or no therapy.[7]Summary: This trial did not show a significant improvement in OS or quality of life. However, the significant and clinically relevant delay in progression may particularly benefit older, less fit patients with myeloma. Early use of daratumumab did not result in a shortened OS after the subsequent initiation of full-dose induction therapy.
The 5-year overall survival (OS) rate was 93% for patients in the daratumumab arm and 86% for patients in the watchful waiting arm (HR, 0.52; 95% CI, 0.27–0.98).
In a prospective randomized trial of 390 patients with smoldering myeloma, patients were eligible if the marrow plasmacytosis was 10% to 49% and one of the following criteria was met: These patients received daratumumab (the anti-CD38 monoclonal antibody) or no therapy.[7]Summary: This trial did not show a significant improvement in OS or quality of life. However, the significant and clinically relevant delay in progression may particularly benefit older, less fit patients with myeloma. Early use of daratumumab did not result in a shortened OS after the subsequent initiation of full-dose induction therapy.
Three quality-of-life assessments showed no difference between the arms.
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