Multiple Myeloma

Multiple myeloma is a type of cancer that arises from plasma cells, the white blood cells that make antibodies.

Standard post-treatment assessment and monitoring

During and after treatment for multiple myeloma, your doctor will conduct laboratory tests of your blood and urine, as well as microscopic examination of your bone marrow at certain intervals, to assess your response to treatment. During treatment you’ll likely have tests done before each new cycle of therapy begins. After treatment you’ll need two consecutive assessments with the same results to be assigned to one of the response categories described below.1

In the months and years after your treatment (you may receive maintenance therapy during this time), your doctor will keep an eye on your health and monitor for signs of relapse using tests of your blood and urine. Every year, or if you show symptoms, your doctor will use X-rays to look for bone lesions. If clinically indicated, your doctor may also do a bone marrow biopsy or a more detailed imaging study using MRI or PET/CT.1

Categories of treatment response:
  • No evidence of M protein in the serum or urine when examined by immunofixation
    • For patients whose disease can only be measured by serum free light chain (FLC) assay, a normal FLC ratio (0.26 to 1.65) is needed in addition to the other CR criteria below
  • No concentrations of cancer cells in the soft tissue
  • Less than 5% plasma cells present in bone marrow

Stringent Complete Response (sCR)

  • All the criteria for CR (above), plus:
    • Normal free light chain ratio (0.26 to 1.65)
    • Absence of myeloma cells when bone marrow is examined with immunohistochemistry or two- to four-color flow cytometry

Immunophenotypic CR (iCR)

  • All of the criteria for sCR (above), plus:
    • No evidence of myeloma cells in the bone marrow when examined using flow cytometry MRD testing (Minimum of 1 million total cells analyzed; more than four colors used)

Molecular CR (mCR)

  • All of the criteria for CR (above), plus:
    • No cancer cells detectable in the bone marrow using ASO-PCR MRD testing
  • M protein detectable in serum and/or urine by immunofixation but not electrophoresis

OR

  • At least 90% reduction in M protein in serum plus urine M protein less than 100 milligrams/24 hours
    • For patients whose disease can only be measured by serum free light chain (FLC) assay, greater than 90% decrease in the difference between involved and uninvolved FLC levels
  • At least 50% decrease in serum M protein plus at least 90% decrease in 24-hour urine M protein or urine M protein less than 200 milligrams/24 hours
    • For patients whose disease can only be measured by serum free light chain (FLC) assay, at least 50% decrease in difference between involved and uninvolved free light chain levels
    • For patients whose serum and urine M protein and serum FLC are not measurable, at least 50% decrease bone marrow plasma cells, provided the baseline amount was at least 30%
  • At least 50% reduction in any soft tissue lesions present at diagnosis
  • No evidence of progressive or new bone lesions if X-rays done
  • Do not have the criteria for CR, VGPR, PR or PD
  • No evidence of progressive or new bone lesions if X-rays done
  • 25% increase of any of the following from the lowest response value:
    • Serum M protein, with absolute increase at least 0.5 grams/deciliter
    • Urine M protein, with absolute increase at least 200 milligrams/24 hours
    • For patients without measurable serum or urine M protein levels whose disease can only be measured by serum free light chain (FLC), the difference between involved and uninvolved levels, with absolute increase more than 10 milligrams/deciliter
    • For patients without measurable serum or urine M protein levels and without measurable disease by serum FLC, bone marrow plasma cells with an absolute increase at least 10%
  • New bone lesions/cancerous cells in the soft tissue or an increase in the size of existing lesions/masses
  • Development of abnormally high calcium levels in the blood attributable only to myeloma

Role of mrd testing

Minimal residual disease (MRD) refers to small numbers of cancer cells that may remain in your body after treatment and eventually cause your disease to come back. These residual cells are present at such low levels that they cannot be detected with the laboratory techniques used for standard post-treatment response assessment and monitoring. Instead, more sensitive tests must be used. The response categories of iCR and mCR described above are determined using types of MRD testing. Next-generation sequencing based MRD testing has also been used for detecting MRD in myeloma patients.2

Studies have shown that myeloma patients treated with high dose chemotherapy followed by autologous (self) stem cell transplantation live longer without their disease progressing (progression-free survival, PFS) and live longer overall (overall survival, OS) if they do not have any MRD detectable in their bone marrow 100 days post-transplant.2-11 Studies suggest the same benefit of MRD-negativity is true in patients who receive allogeneic (donor) transplants.7, 12 Finally, in patients receiving only induction therapy (no transplant of any kind), prognosis is also better in those patients who reach a MRD-negative state.2, 4-7, 9, 13

The benefit of reaching MRD-negativity holds even when researchers look only at myeloma patients in CR – i.e., among patients in CR who all appear to have reached the deepest level of response measurable by standard criteria, there are different groups with different outcomes when MRD testing is used to look deeper.2, 4-11, 13

next steps

Find resources that can help you prepare to talk with your doctor about disease level testing and how it might play a part in your treatment plan.