Is a new rise in monocytes (MONO) absolute count to 1.6 x10^9/L concerning in a patient with multiple myeloma who is currently off treatment?

Elevated Monocyte Count in Multiple Myeloma Off Treatment

An absolute monocyte count of 1.6 × 10⁹/L in a patient with multiple myeloma currently off treatment is concerning and warrants further evaluation for disease progression, though it is not by itself a criterion for relapse or progression according to established guidelines.

Why This Finding Matters

The elevated monocyte count is concerning for several reasons:

• Monocyte elevation correlates with tumor burden: Research demonstrates that abnormal absolute monocyte counts (AMC) are associated with inferior overall survival in multiple myeloma patients, with severely elevated AMC (≥1.25 × 10³/mm³, equivalent to 1.25 × 10⁹/L) showing median OS of only 2.7 years versus 3.6 years for normal AMC 1.

• Your patient's value of 1.6 × 10⁹/L exceeds the severely elevated threshold, placing them in the highest risk category for adverse outcomes 1.

• Monocyte subsets shift with disease activity: The proportion of non-classical and intermediate monocytes increases with plasma cell burden and correlates positively with markers of disease severity including M-protein, calcium, creatinine, and lactate dehydrogenase 2.

• Dynamic prognostic significance: Patients who develop abnormal AMC more than 1 year after diagnosis experience inferior OS compared to those maintaining normal AMC, indicating this is a dynamic marker of disease status 1.

What This Does NOT Mean

This finding alone does not meet criteria for disease progression or relapse according to International Myeloma Working Group (IMWG) guidelines 3.

Established relapse criteria require one or more of the following 3:

• ≥25% increase in serum M-protein (absolute increase ≥5 g/L)
• ≥25% increase in 24-hour urine light chains (absolute increase ≥200 mg/24h)
• ≥25% increase in bone marrow plasma cells (absolute increase ≥10%)
• Development of new bone lesions or soft tissue plasmacytomas
• Hypercalcemia (>11.5 mg/dL) not attributable to other causes 4
• Decrease in hemoglobin >2 g/dL or to <10 g/dL
• Rise in creatinine ≥2 mg/dL

Monocyte count is not included in these criteria.

Recommended Clinical Approach

Immediately assess for formal relapse criteria:

1. Check myeloma-specific markers 3:

   • Serum and urine protein electrophoresis with immunofixation
   • Serum free light chains with ratio
   • Complete blood count (assess for anemia)
   • Comprehensive metabolic panel (calcium, creatinine)
   • Bone marrow biopsy if other markers are equivocal

2. Evaluate for clinical relapse indicators 3:

   • New or worsening bone pain
   • Imaging (skeletal survey, MRI, or PET-CT) for new lytic lesions or plasmacytomas
   • Assess for hypercalcemia, renal dysfunction, or symptomatic anemia

3. Consider the monocyte elevation in context 1:

   • If other myeloma markers are stable and no CRAB features present, the elevated monocyte count serves as an early warning sign requiring closer monitoring
   • Repeat assessment in 1-2 months rather than standard 3-month intervals
   • If myeloma markers show ≥25% increases or CRAB features develop, initiate treatment per relapsed myeloma algorithms 3

Common Pitfalls to Avoid

• Do not initiate myeloma treatment based solely on monocyte elevation: This would constitute overtreatment, as monocyte count is not an established treatment trigger 3.

• Do not dismiss this finding: While not diagnostic of progression, abnormal AMC independently predicts inferior outcomes even after adjusting for International Staging System and LDH 1.

• Rule out alternative causes of monocytosis: Infection, inflammation, other hematologic disorders, or medications can elevate monocytes independent of myeloma activity 5.

• Avoid delaying evaluation: The combination of known myeloma and new laboratory abnormality mandates prompt assessment for progression, as delays in treating true relapse increase morbidity and mortality 6.

Clinical Context

The biological mechanism underlying this association involves monocyte-derived myeloid suppressor cells and tumor-associated macrophages that support malignant plasma cell proliferation in the bone marrow microenvironment 1, 7. The peripheral blood monocyte count appears to reflect this pathologic bone marrow milieu 1.

In summary: Treat this as a red flag requiring comprehensive myeloma assessment, but not as an independent indication to restart therapy.