MM Flashcards
If whole-body low-dose CT or FDG-PET/ CT is negative, consider ____________ to discern smoldering myeloma from multiple myeloma (MM)
Whole-body MRI without contrast
CT contrast agents are not necessary for detection of myeloma bone disease and should generally be avoided in myeloma patients whenever possible.
The FISH panel for prognostic estimation of plasma cells should be examined for
- del(13)
- del(17p13)
- t(4;14)
- t(11;14)
- t(14;16)
- t(14:20)
- 1q21 gain/amplification
- 1p deletion
Primary treatment for: Solitary plasmacytoma or Solitary plasmacytoma with minimal marrow involvement
Solitary plasmacytoma with 10% or more clonal plasma cells is regarded as active (symptomatic) MM and systemic therapy should be considered.
RTm ± surgery
or Consider clinical trial
Systemic therapy may be considered in patients with high risk of progression based on the clinical context.
Follow-up interval for evaluation in: Solitary plasmacytoma or Solitary plasmacytoma with minimal marrow involvement after RT
Every 3–6 mo
All plasmacytomas should be imaged _________ , preferably with the same technique used at diagnosis, for at least 5 years
Yearly
Considered as High risk Smoldering myeloma
- Bone marrow plasma cells (BMPCs) > 20%
- M-protein > 2 g/dL
- Serum FLC ratio (FLCr) > 20
The Mayo 2018/IMWG 20/2/20 criteria
Patients with two or more of these risk factors are considered to have high risk of progression to MM.
Preferred treatment for High risk Smoldering myeloma
3 months
Medication that can be considered for High risk Smoldering myeloma
Lenalidomide
TRUE OR FALSE
Immunofixation is needed only if protein electrophoresis is negative during follow-up.
TRUE
Immunofixation is needed only if protein electrophoresis is negative during follow-up.
TRUE OR FALSE
Renal dysfunction and advanced age are contraindications to transplant.
FALSE
Renal dysfunction and advanced age are not contraindications to transplant.
TRUE OR FALSE
Patients with stable disease can be considered for autologous HCT.
TRUE
Patients with stable disease can be considered for autologous HCT.
Options if there is response after primary therapy
- Autologous HCT(category 1)
- Continuous myeloma therapy or maintenance therapy
- Tandem autologous or allogeneic HCT for patients with high-risk of progression/relapse, under certain circumstances
Criteria
Smoldering Myeloma (Asymptomatic)
- Serum monoclonal protein ≥3 g/dL or Bence-Jones protein ≥500 mg/24 h
and/or - Clonal bone marrow plasma cells (BMPCs) 10%–59%
and - Absence of myeloma-defining events or amyloidosis
Criteria
Multiple Myeloma (Symptomatic)
- Clonal BMPCs ≥10% or biopsy-proven bony or extramedullary plasmacytoma
and
Any one or more of the following myeloma-defining events:
* 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 FDG-PET/CT
* Clonal BMPCs ≥ 60%
* Involved:uninvolved serum FLC ratio (FLCr) ≥ 100 and involved FLC concentration 10 mg/dL or higher
* >1 focal lesions on MRI studies ≥ 5 mm
SLiM-CRAB
Factors Considered as High Risk for Progression/Relapse
For Those with Newly Diagnosed MM
- R-ISS III
- Extramedullary disease
- Circulating plasma cells
- Cytogenetic abnormalities
�Del(1p32)
�t(4;14)
�t(14;16)
�t(14;20)
�Del(17p)/monosomy 17/TP53 mutation
�1q21 gain/1q21 amplificationb
� MYC translocation - High-risk gene expression profile
1q21 gain/amplification alone is not considered high-risk for progression/relapse.
Factors Considered as High Risk for Progression/Relapse
For Those with Relapsed MM
- Disease relapse within 2 years of initial therapy when transplant and maintenance are used.
- Relapse within 18 mo in case of nontransplant–
based treatment. - Acquisition of 1q gain/amplification and/or del(17p)/TP53 mutation
- Extramedullary disease at relapse
Presence of ≥ _____ % of plasma cells in circulation is defined as plasma cell leukemia.
≥5%
International Staging System (ISS)
- I: Serum beta-2 microglobulin <3.5 mg/L, Serum albumin ≥3.5 g/dL
- II: Not ISS stage I or III
- III: Serum beta-2 microglobulin ≥5.5 mg/L
Revised-ISS (R-ISS)
- I: ISS stage I and standard-risk chromsomal abnormalities by FISH and Serum LDH ≤ the upper limit of normal
- II: Not R-ISS stage I or III
- III: ISS stage III and either high-risk chromosomal abnormalities by FISH or Serum LDH > the upper limit of normal
R2-ISS
R2-ISS is only validated for newly diagnosed Multiple Myeloma.
A numerical value is assigned to each risk factor based on their influence on OS:
* ISS-III is 1.5 points
* ISS-II is 1 point
* del(17p) is 1 point
* t(4;14) is 1 point
* 1q+ is 0.5 points and
* serum LDH > the upper limit of normal is 1 point
- Low-risk: 0 points
- Low-intermediate risk: 0.5–1 points
- Intermediate-high risk: 1.5–2.5 points
- High-risk: 3–5 points
Recommended for initial diagnostic workup of patients suspected of having MM or solitary
plasmacytoma
Whole-body low-dose CT or FDG-PET/CT
Skeletal survey is acceptable in certain circumstances.
The first choice for initial evaluation of solitary osseous plasmacytoma
Whole-body MRI (or FDG-PET/CT if MRI is not available)
Wholebody FDG-PET/CT is the first choice for initial evaluation of solitary extraosseous plasmacytoma.
Clinical target colume (CTV) expansions should generally include at least ______ cm of margin for microscopic extent, and up to ____ cm for involvement of long bones.
0.5 cm
2–3 cm
RT dose for solitary plasmacytoma
RT (40–50 Gy in 1.8–2.0 Gy fractions [20–25 total fractions])
Treatment with 35–40 Gy is an acceptable alternative for solitary plasmacytomas < 5 cm in size, due to the high rates of local control reported for smaller tumors.
TRUE OR FALSE
RT is primarily used for palliation in patients with MM.
TRUE
RT is primarily used for palliation in patients with MM.
Systemic therapy should not be delayed for RT, and can often be given concurrently.
Palliative RT Dosing for MM:
Low-dose RT (8 Gy x 1 fraction) or 20–30 Gy in 5–10 total fractions can be used as palliative treatment for uncontrolled pain, for impending pathologic fracture, or for impending cord compression.
Moderately fractionated courses of 20-25 Gy in 8-10 fractions are generally preferred over higher doses (30 Gy) absent extenuating circumstances (e.g., severe symptomatic cord compression) to limit unnecessary toxicity and reduce risk of future treatment of
adjacent or overlapping organs at risk (e.g., spinal cord).
Standard IMWG response criteria
Stringent complete response
- Complete response plus
- Normal FLC ratio and
- Absence of clonal cells in bone marrow biopsy by immunohistochemistry (κ/λ ratio ≤4:1 or ≥1:2 for κ and λ patients, respectively, after counting ≥100 plasma cells).
The FLCr is required for documenting sCR according to the IMWG Uniform Response Criteria.
The serum FLC assay cannot replace the 24-hour UPEP for monitoring patients with measurable urinary M protein and can also be affected by renal function.
Standard IMWG response criteria
Complete response
- Negative immunofixation on the serum and urine and
- Disappearance of any soft tissue plasmacytomas and
- <5% plasma cells in bone marrow aspirates
Standard IMWG response criteria
Very good partial response
- Serum and urine M-protein detectable by immunofixation but not on electrophoresis or
- ≥90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 h
Standard IMWG response criteria
Partial response
- ≥50% reduction of serum M-protein plus
- Reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 h.
- If the serum and urine M-protein are unmeasurable, a ≥ 50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria.
- If serum and urine M-protein are unmeasurable, and serum-free light assay is also unmeasurable, ≥ 50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma-cell percentage was ≥30%.
- In addition to these criteria, if present at baseline, a ≥ 50% reduction in the size (sum of the products of the maximal perpendicular diameters [SPD] of measured lesions)j of soft tissue plasmacytomas is also required.
Standard IMWG response criteria
Minimal response
- ≥ 25% but ≤49% reduction of serum M-protein and
- Reduction in 24-h urine M-protein by 50%–89%.
- In addition to the above listed criteria, if present at baseline, a 25%–49% reduction in SPDj of soft tissue plasmacytomas is also required.
Standard IMWG response criteria
Stable disease
Not meeting criteria for complete response, very good partial response, partial response, minimal
response, or progressive disease.
Not recommended for use as an indicator of response; stability of disease is best described by providing the time-toprogression estimates
Standard IMWG response criteria
Progressive disease
Any one or more of the following criteria:
* Increase of 25% from lowest confirmed response value in one or more of the following criteria:
>Serum M-protein (absolute increase must be ≥0.5 g/dL);
>Serum M-protein increase ≥1 g/dL, if the lowest M component was ≥5 g/dL;
>Urine M-protein (absolute increase must be ≥200 mg/24 h);
- In patients without measurable serum and urine M-protein levels, the difference between involved and uninvolved FLC levels (absolute increase must be >10 mg/dL);
- In patients without measurable serum and urine M-protein levels and without measurable involved FLC levels, bone marrow plasma-cell percentage irrespective of baseline status (absolute increase must be ≥10%);
- Appearance of a new lesion(s), ≥50% increase from nadir in SPDj of >1 lesion, or ≥50% increase in the longest diameter of a previous lesion >1 cm in short axis;
- ≥ 50% increase in circulating plasma cells (minimum of 200 cells per μL) if this is the only measure of disease
Standard IMWG response criteria
Clinical relapse
- Direct indicators of increasing disease and/or end organ dysfunction (calcium elevation, renal failure, anemia, lytic bone lesions [CRAB features]) related to the underlying clonal plasma cell proliferative disorder.
- Development of new soft tissue plasmacytomas or bone lesions (osteoporotic fractures do not constitute progression);
- Definite increase in the size of existing plasmacytomas or bone lesions.
A definite increase is defined as a 50% (and ≥1 cm)
increase as measured serially by the SPDj of the measurable lesion; - Hypercalcemia (>11 mg/dL);
- Decrease in hemoglobin of ≥2 g/dL not related to therapy or other non–myeloma-related conditions;
- Rise in serum creatinine by 2 mg/dL or more from the start of the therapy and attributable to myeloma;
- Hyperviscosity related to serum paraprotein
It is not used in calculation of time to progression or progression-free survival but is listed as something that can be reported optionally or for use in clinical practice;
Standard IMWG response criteria
Relapse from complete response
(to be used only if the endpoint is disease-free survival)
Any one or more of the following criteria:
* Reappearance of serum or urine M-protein by immunofixation or electrophoresisi;
* Development of ≥5% plasma cells in the bone marrow;
* Appearance of any other sign of progression (ie, new plasmacytoma, lytic bone lesion, or hypercalcemia) (see above).
Standard IMWG response criteria
Relapse from MRD negative
(to be used only if the endpoint is disease-free survival)
Any one or more of the following criteria:
* Loss of MRD negative state (evidence of clonal plasma cells on NGF or NGS, or positive imaging study for recurrence of myeloma);
* Reappearance of serum or urine M-protein by immunofixation or electrophoresis;
* Development of ≥5% clonal plasma cells in the bone marrow;
* Appearance of any other sign of progression (ie, new plasmacytoma, lytic bone lesion, or hypercalcemia).
