From the Guidelines
Multiple myeloma exacerbation can be identified through several key indicators, including worsening symptoms, laboratory tests showing rising levels of monoclonal proteins, and imaging studies revealing new or enlarging bone lesions, as outlined in the 2017 NCCN clinical practice guidelines 1.
Key Indicators of Exacerbation
- Worsening symptoms such as increased bone pain, fatigue, recurrent infections, or unexplained weight loss
- Laboratory tests showing:
- Rising levels of monoclonal proteins (M-protein) in blood or urine
- Increasing calcium levels
- Worsening anemia
- Declining kidney function
- Elevated beta-2 microglobulin
- Imaging studies revealing:
- New or enlarging bone lesions
- Pathological fractures
- Spinal cord compression
Disease-Defining Events
According to the 2017 NCCN guidelines 1, myeloma-defining events include:
- Calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL)
- Renal insufficiency (creatinine >2 mg/dL) [>177 μmol/L] or creatinine clearance <40 mL/min
- Anemia (hemoglobin <10 g/dL or hemoglobin >2 g/dL below the lower limit of normal)
- One or more osteolytic bone lesions on skeletal radiography, CT, or PET/CT
- Clonal bone marrow plasma cells ≥60%
- Abnormal serum FLC ratio ≥100 (involved kappa) or ≤0.01 (involved lambda)
1 focal lesions on MRI studies ≥5 mm
Monitoring and Management
Patients should maintain regular follow-up appointments with their oncologist for monitoring through blood tests, urine tests, and periodic imaging, as recommended by the European Myeloma Network guidelines 1. Disease exacerbation requires prompt medical attention, and early intervention with adjusted treatment regimens can help control disease progression and prevent serious complications like kidney failure or skeletal events, as emphasized in the Italian Society of Hematology guidelines 1.
From the FDA Drug Label
Table 9: ELOQUENT-3: Adverse Reactions with a 10% or Higher Incidence for EMPLICITI-Treated Patients and a 5% or Higher Incidence than Pomalidomide and Dexamethasone-Treated Patients [All Grades]
EMPLICITI + Pomalidomide and Dexamethasone N=60 Pomalidomide and Dexamethasone N=55 Adverse Reaction All Grades Grade 3/4 All Grades Grade 3/4
- The term pneumonia is grouping of the following terms: pneumonia, atypical pneumonia, lower respiratory tract infection, pneumoccocal sepsis, pneumonia bacterial, pneumonia influenza. Constipation 22 1.7 11 0 Hyperglycemia 20 8 15 7 Pneumonia* 18 10 13 11 Diarrhea 18 0 9 0 Respiratory Tract Infection 17 0 9 1.8 Bone Pain 15 3.3 9 0 Dyspnea 15 3.3 7 1.8 Muscle Spasms 13 0 5 0 Edema Peripheral 13 0 7 0 Lymphopenia 10 8 1.8 1.
The signs of multiple myeloma (Plasma Cell Myeloma) exacerbation include:
- Pneumonia (18% of patients)
- Hyperglycemia (20% of patients)
- Diarrhea (18% of patients)
- Respiratory Tract Infection (17% of patients)
- Bone Pain (15% of patients)
- Dyspnea (15% of patients)
- Lymphopenia (10% of patients)
- Other adverse reactions such as constipation, muscle spasms, and edema peripheral 2
From the Research
Signs of Multiple Myeloma Exacerbation
The signs of multiple myeloma exacerbation can be identified through various diagnostic criteria and symptoms, including:
- Hypercalcemia (elevated calcium levels) 3, 4, 5
- Renal failure (kidney damage) 3, 4, 5
- Anemia (low red blood cell count) 3, 4, 5
- Lytic bone lesions (bone damage) 3, 4, 5
- Elevated serum lactate dehydrogenase (LDH) levels 6
- Presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation, which are considered high-risk factors 3, 4
- Bone marrow clonal plasmacytosis ≥60% 3, 4
- Serum involved/uninvolved free light chain (FLC) ratio ≥100 3, 4
Diagnostic Criteria
The diagnosis of multiple myeloma requires:
- ≥10% clonal bone marrow plasma cells or a biopsy-proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE) 3, 4
- Evaluation of patients with possible multiple myeloma includes measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels; serum protein electrophoresis with immunofixation; 24-hour urine protein electrophoresis; and full-body skeletal imaging with computed tomography, positron emission tomography, or MRI 5
Treatment and Management
Treatment of multiple myeloma involves:
- Induction therapy with a combination of an injectable proteasome inhibitor, an oral immunomodulatory agent, and dexamethasone 3, 6, 4, 5
- Autologous hematopoietic stem cell transplantation followed by maintenance lenalidomide for eligible patients 3, 4, 5
- Treatment with daratumumab, lenalidomide, and dexamethasone (DRd) until progression for frail patients who are not candidates for transplant 3, 4
- A triplet regimen is usually needed at relapse, with the choice of regimen varying with each successive relapse 3, 4, 7