Signs and Symptoms of Multiple Myeloma Relapse: What Patients and Caregivers Should Know

When multiple myeloma returns, the signs often mirror those seen during initial diagnosis. The clinical criteria used to define active disease remain consistent—commonly referred to as CRAB symptoms. These include Calcium elevation, Renal (kidney) dysfunction, Anemia, and Bone lesions. If a patient experiences any of these manifestations, it typically indicates active disease progression and warrants prompt therapeutic intervention.

Understanding CRAB Criteria in Disease Recurrence

The CRAB acronym serves as a foundational framework for identifying symptomatic multiple myeloma relapse:

Hypercalcemia: Elevated calcium levels can lead to fatigue, confusion, excessive thirst, and kidney issues.
Renal insufficiency: Impaired kidney function, often detected through increased serum creatinine, may result from excess light chains damaging renal tubules.
Anemia: A drop in red blood cell count commonly causes weakness, shortness of breath, and persistent tiredness.
Bone pain or lytic lesions: Bone destruction due to plasma cell infiltration can cause severe pain, fractures, or spinal compression.

Meeting one or more of these criteria generally confirms the need for reinitiating treatment.

Biochemical Relapse: Detecting Myeloma Before Symptoms Appear

Thanks to improved monitoring protocols, many patients are now diagnosed at earlier stages of relapse—even before physical symptoms develop. This stage is known as biochemical relapse, characterized solely by abnormal laboratory findings such as rising M-protein levels, increasing serum free light chains, or a growing percentage of clonal plasma cells in the bone marrow, without any clinical symptoms.

Most international guidelines, including those from the International Myeloma Working Group (IMWG), recommend a "watch and wait" approach during this phase. Active treatment is usually not advised unless specific high-risk markers emerge. Instead, patients undergo regular blood tests, urine analyses, and imaging studies to monitor disease activity closely.

The SLiM Criteria: When to Start Treatment Without Symptoms

In recent years, the definition of active myeloma has expanded beyond CRAB to include biomarkers that predict imminent organ damage. The IMWG introduced the SLiM criteria to identify patients who should begin therapy even in the absence of traditional symptoms:

S: ≥60% clonal plasma cells in the bone marrow
Li: Serum free light chain ratio ≥100 (with the involved light chain level ≥100 mg/L)
M: More than one focal lesion measuring ≥5 mm on MRI

Meeting any one of these SLiM criteria classifies the condition as active multiple myeloma, requiring immediate treatment regardless of symptom presence.

Why Early Detection Matters

Patients today are more informed and engaged in their care than ever before. With greater awareness and access to advanced diagnostics like PET-CT, whole-body MRI, and sensitive minimal residual disease (MRD) testing, both clinicians and patients prioritize proactive surveillance.

This shift allows for earlier detection of disease recurrence, potentially improving long-term outcomes by initiating therapy before irreversible organ damage occurs. It also supports personalized treatment planning, helping oncologists choose targeted therapies, immunomodulatory drugs, monoclonal antibodies, or enrollment in clinical trials based on individual risk profiles.

Conclusion: Staying Ahead of the Curve

Recognizing the signs of multiple myeloma relapse—whether through classic CRAB features or asymptomatic SLiM indicators—is crucial for timely intervention. Regular follow-ups, adherence to monitoring schedules, and open communication with healthcare providers empower patients to stay ahead of disease progression and maintain a better quality of life throughout their journey.