MM

Question 1

If whole-body low-dose CT or FDG-PET/ CT is negative, consider ____________ to discern smoldering myeloma from multiple myeloma (MM)

Answer 1

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.

Question 2

The FISH panel for prognostic estimation of plasma cells should be examined for

Answer 2

• del(13)
• del(17p13)
• t(4;14)
• t(11;14)
• t(14;16)
• t(14:20)
• 1q21 gain/amplification
• 1p deletion

Question 3

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.

Answer 3

RTm ± surgery
or Consider clinical trial

Systemic therapy may be considered in patients with high risk of progression based on the clinical context.

Question 4

Follow-up interval for evaluation in: Solitary plasmacytoma or Solitary plasmacytoma with minimal marrow involvement after RT

Answer 4

Every 3–6 mo

Question 5

All plasmacytomas should be imaged _________ , preferably with the same technique used at diagnosis, for at least 5 years

Answer 5

Yearly

Question 6

Considered as High risk Smoldering myeloma

Answer 6

• 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.

Question 7

Preferred treatment for High risk Smoldering myeloma

Answer 7

3 months

Question 8

Medication that can be considered for High risk Smoldering myeloma

Answer 8

Lenalidomide

Question 9

TRUE OR FALSE

Immunofixation is needed only if protein electrophoresis is negative during follow-up.

Answer 9

TRUE

Immunofixation is needed only if protein electrophoresis is negative during follow-up.

Question 10

TRUE OR FALSE

Renal dysfunction and advanced age are contraindications to transplant.

Answer 10

FALSE

Renal dysfunction and advanced age are not contraindications to transplant.

Question 11

TRUE OR FALSE

Patients with stable disease can be considered for autologous HCT.

Answer 11

TRUE

Patients with stable disease can be considered for autologous HCT.

Question 12

Options if there is response after primary therapy

Answer 12

• 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

Question 13

Criteria

Smoldering Myeloma (Asymptomatic)

Answer 13

• 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

Question 14

Criteria

Multiple Myeloma (Symptomatic)

Answer 14

• 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

Question 15

Factors Considered as High Risk for Progression/Relapse

For Those with Newly Diagnosed MM

Answer 15

• 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.

Question 16

Factors Considered as High Risk for Progression/Relapse

For Those with Relapsed MM

Answer 16

• 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

Question 17

Presence of ≥ _____ % of plasma cells in circulation is defined as plasma cell leukemia.

Answer 17

≥5%

Question 18

International Staging System (ISS)

Answer 18

• 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

Question 19

Revised-ISS (R-ISS)

Answer 19

• 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

Question 20

R2-ISS

R2-ISS is only validated for newly diagnosed Multiple Myeloma.

Answer 20

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

Question 21

Recommended for initial diagnostic workup of patients suspected of having MM or solitary
plasmacytoma

Answer 21

Whole-body low-dose CT or FDG-PET/CT

Skeletal survey is acceptable in certain circumstances.

Question 22

The first choice for initial evaluation of solitary osseous plasmacytoma

Answer 22

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.

Question 23

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.

Answer 23

0.5 cm

2–3 cm

Question 24

RT dose for solitary plasmacytoma

Answer 24

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.

Question 25

# TRUE OR FALSE RT is primarily used for palliation in patients with MM.

Answer 25

TRUE RT is primarily used for **palliation** in patients with MM. ## Footnote **Systemic therapy should not be delayed for RT**, and can often be given **concurrently**.

Question 26

Palliative RT Dosing for MM:

Answer 26

**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. ## Footnote 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).

Question 27

# Standard IMWG response criteria Stringent complete response

Answer 27

* 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). ## Footnote 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.

Question 28

# Standard IMWG response criteria Complete response

Answer 28

* Negative immunofixation on the serum and urine and * Disappearance of any soft tissue plasmacytomas and * <5% plasma cells in bone marrow aspirates

Question 29

# Standard IMWG response criteria Very good partial response

Answer 29

* 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

Question 30

# Standard IMWG response criteria Partial response

Answer 30

* ≥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.

Question 31

# Standard IMWG response criteria Minimal response

Answer 31

* **≥ 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 SPD of soft tissue plasmacytomas is also required.

Question 32

# Standard IMWG response criteria Stable disease

Answer 32

Not meeting criteria for complete response, very good partial response, partial response, minimal response, or progressive disease. ## Footnote **Not recommended for use as an indicator of response**; stability of disease is best described by providing the **time-to-progression estimates**

Question 33

# Standard IMWG response criteria Progressive disease

Answer 33

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

Question 34

# Standard IMWG response criteria Clinical relapse

Answer 34

* 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 SPD 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 ## Footnote 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;

Question 35

# Standard IMWG response criteria Relapse from complete response ## Footnote (to be used only if the endpoint is disease-free survival)

Answer 35

Any one or more of the following criteria: * Reappearance of serum or urine M-protein by immunofixation or electrophoresis; * 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).

Question 36

# Standard IMWG response criteria Relapse from MRD negative ## Footnote (to be used only if the endpoint is disease-free survival)

Answer 36

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).

Question 37

# TRUE OR FALSE All response categories require two consecutive assessments made any time before starting any new therapy.

Answer 37

TRUE All response categories require **two consecutive assessments** made any time before starting any new therapy. ## Footnote *For MRD there is no need for two consecutive assessments*, but information on MRD after each treatment stage is recommended (eg, after induction, high-dose therapy/ Autologous stem cell transplants (ASCT), consolidation, maintenance). *Radiographic studies are not required to satisfy these response requirements. * *Bone marrow assessments do not need to be confirmed. *

Question 38

When the only method to measure disease is by serum FLC levels:

Answer 38

* **Complete response**: a normal FLC ratio of 0.26 to 1.65 in addition to the complete response criteria * **Very good partial response** in such patients requires a **≥90%** decrease in the difference between involved and uninvolved FLC levels.

Question 39

Patients should receive at least a ____________ regimen if they can tolerate it.

Answer 39

Triplet regimen (2 drug classes and steroids) ## Footnote Patients with **poor performance status or who are frail** can be started on a **2-drug regimen**, with a third drug added once performance status improves. Consider dose modifications based on functional status and age.

Question 40

For **relapsed** disease, if relapse is greater than _____ months after the end of primary treatment, the **regimen used for primary therapy may be repeated.**

Answer 40

6 months

Question 41

# TRUE OR FALSE: R/R Myeloma A new triplet regimen should preferably include drugs or drug classes patients have not been exposed to, or not exposed to for at least 6 months.

Answer 41

TRUE A new triplet regimen should preferably include **drugs or drug classes patients have not been exposed to, or not exposed to for at least 6 months**.

Question 42

**Intravenous immunoglobulin (IVIG)** should be considered for patients with an IgG _____ mg/dL prior to the administration of **bispecfic T-cell antibodies and CAR T-cell therapy.**

Answer 42

IgG <400 mg/dL

Question 43

Consider harvesting peripheral blood stem cells within the _________ cycles of therapy initiation prior to prolonged exposure to **lenalidomide and/or daratumumab** in patients for whom HCT is being considered.

Answer 43

Within the first 6 cycles of therapy ## Footnote Exposure to **myelotoxic agents (including alkylating agents and nitrosoureas)** should be **limited** to avoid compromising stem cell reserve prior to stem cell harvest in patients who may be candidates for HCT. ***notably Melphalan

Question 44

Preferred method of administration of bortezomib

Answer 44

Subcutaneous ## Footnote Both weekly and twice-weekly dosing schemas of bortezomib may be appropriate; **weekly preferred.** Carfilzomib may be used once or twice weekly and at different doses.

Question 45

# TRUE OR FALSE Daratumumab and hyaluronidase-fihj for subcutaneous injection has same dosing with daratumumab for intravenous infusion.

Answer 45

FALSE Daratumumab and hyaluronidase-fihj for subcutaneous injection has **different dosing** and administration instructions compared to daratumumab for intravenous infusion.

Question 46

**Steroids** should be reduced to ________ mg weekly in **older** patients and should be decreased or discontinued with **treatment response plateau and/ or toxicity**.

Answer 46

20 mg weekly

Question 47

Medications that may interfere with serologic testing and cause **false-positive indirect Coombs test.**

Answer 47

Daratumumab and isatuximab-irfc ## Footnote Type and screen should be performed before using daratumumab or isatuximab-irfc.

Question 48

Drug that can produce a **false positive serum immunofixation** if the monoclonal protein is **IgG kappa**

Answer 48

Monoclonal antibodies ## Footnote **Special interference testing or mass spectrometry** based assessment can differentiate between the two.

Question 49

Drug that can potentially cause **cardiac and pulmonary toxicity**, especially in older patients.

Answer 49

Carfilzomib

Question 50

Drug that can impact the ability to collect T cells for CAR T-cell therapy.

Answer 50

Bendamustine

Question 51

Preferred Regimens for **Transplant Candidates**

Answer 51

* Bortezomib/lenalidomide/dexamethasone (category 1) * Carfilzomib/lenalidomide/dexamethasone ## Footnote Other Recommended Regimens * Daratumumab/lenalidomide/bortezomib/dexamethasone

Question 52

Regimen preferred primarily as initial treatment in patients with **acute renal insufficiency** or those who have **no access** to proteasome inhibitor (PI)/lenalidomide/ dexamethasone.

Answer 52

* Bortezomib/cyclophosphamide/dexamethasone * Carfilzomib/cyclophosphamide/dexamethasone ## Footnote Consider switching to PI/lenalidomide/dexamethasone after renal function improves.

Question 53

Treatment option for patients with renal insufficiency and/or peripheral neuropathy.

Answer 53

Carfilzomib/cyclophosphamide/dexamethasone

Question 54

Generally reserved for the treatment of aggressive MM

Answer 54

Dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide/bortezomibg (VTD-PACE)

Question 55

Drug that appears to have an increased risk for **secondary cancer**s, especially with maintenance following transplant. .

Answer 55

Lenalidomide ## Footnote The benefits and risks of maintenance therapy vs. secondary cancers should be discussed with patients

Question 56

Preferred Regimens for **Maintainance-Transplant Candidates**

Answer 56

Lenalidomide (category 1) ## Footnote Other Recommended Regimens: Bortezomib Two drug maintenance recommended for high-risk MM Results from interim analyses of TOURMALINE MM3 and MM4 trials of **ixazomib** in the maintenance setting suggest a **potential decrease in overall survival (OS)**. Patients with high-risk cytogenetics have been shown to benefit from a combination of PI and IMiD as maintenance therapy

Question 57

Refers to a planned second course of high-dose therapy and HCT within 6 months of the first course An option for patients who do not achieve at least a VGPR after the first autologous HCT and those with high-risk features

Answer 57

Tandem HCT ## Footnote The NCCN Multiple Myeloma Panel recommends collecting enough hematopoietic stem cells for at least one HCT in all eligible patients, and for two transplants in the younger patients if tandem transplant or repeat transplant would be considered.

Question 58

Preferred Regimens for **Non-Transplant Candidates**

Answer 58

* Bortezomib/lenalidomide/dexamethasone (category 1) * Daratumumab/lenalidomide/dexamethasone (category 1) ## Footnote Other Recommended Regimens: * Daratumumab/bortezomib/melphalan/prednisone (category 1) * Carfilzomib/lenalidomide/dexamethasone * Daratumumab/cyclophosphamide/bortezomib/dexamethasone

Question 59

Regimen for Non-Transplant Candidates that can be given continuously until progression

Answer 59

Lenalidomide/low-dose dexamethasone (category 1)

Question 60

Regimen for Non-Transplant Candidates that can be given for frail patients

Answer 60

Bortezomib/lenalidomide/dexamethasone (VRD-lite)

Question 61

Preferred Regimens for **Maintainance-Non-Transplant Candidates**

Answer 61

Lenalidomide (category 1) ## Footnote Other Recommended Regimens: Bortezomib Patients with high-risk cytogenetics have been shown to benefit from a combination of PI and IMiD as maintenance therapy

Question 62

CAR T-Cell Therapy for MM

Answer 62

* **Ciltacabtagene autoleucel** (category 1)- After one prior therapy including IMiD and a PI, and refractory to lenalidomide * **Idecabtagene vicleucel** (category 1)- After two prior therapies including an IMiD, an anti-CD38 monoclonal antibody and a PI

Question 63

Preferred Regimens for **Relapsed/Refractory Disease After 3 Prior Therapies**

Answer 63

After at least four prior therapies, including an anti-CD38 monoclonal antibody, a PI, and an IMiDs **CAR T-cell Therapy:** ◊ Ciltacabtagene autoleucel ◊ Idecabtagene vicleucel **Bispecific Antibodies:** ◊ Elranatamab-bcmm ◊ Talquetamab-tgvs ◊ Teclistamab-cqyv ## Footnote Other Recommended Regimens: * Bendamustine * Bendamustine/bortezomib/dexamethasone * Bendamustine/carfilzomib/dexamethasone * Bendamustine/lenalidomide/dexamethasone * High-dose or fractionated cyclophosphamide

Question 64

Can be used after at least three prior therapies including a PI and an IMiD or are doublerefractory to a PI and an IMiD

Answer 64

Daratumumab

Question 65

Can be used for t(11;14) patients

Answer 65

Venetoclax/dexamethasone ± daratumumab or PI only

Question 66

Can be used after at least four prior therapies, including an anti-CD38 monoclonal antibody, a PI, and an IMiD

Answer 66

Selinexor/dexamethasone Belantamab mafodotin-blmf

Question 67

A BCMA antibody, conjugated to a microtubule disrupting agent— monomethyl auristatin—via a stable, protease resistant linker

Answer 67

Belantamab mafodotin-blmf

Question 68

Bone-targeting medication preferred in patients with renal insufficiency

Answer 68

Denosumab

Question 69

Bone-targeting treatment (bisphosphonates or denosumab) should be continued for up to ______ years.

Answer 69

2 years ## Footnote The frequency of dosing (monthly vs. every 3 months) would depend on the individual patient criteria, response to therapy, and agent used. Continuing beyond 2 years should be based on clinical judgment.

Question 70

Consider _________________ for symptomatic **vertebral compression fractures**.

Answer 70

Vertebroplasty or kyphoplasty ## Footnote **Orthopedic consultation** should be sought for impending or actual long-bone fractures or bony compression of spinal cord or vertebral column instability.

Question 71

Management of hypercalcemia

Answer 71

* Hydration * Bisphosphonates (zoledronic acid preferred), denosumab * Steroids and/or * Calcitonin

Question 72

Therapy for symptomatic hyperviscosity

Answer 72

Plasmapheresis

Question 73

Factors associated with an increased risk of infections in patients with MM:

Answer 73

* Autologous HCT * Bispecific antibody (BsAb) therapy * CAR T-cell therapy * Cytotoxic chemotherapy * **New diagnosis of MM** has an increased risk of **bacterial** infection. * **Proteasome inhibitors and monoclonal antibodies** have an increased risk of **viral** infection. * **High-dose steroids** have an increased risk of **fungal** infections.

Question 74

VTE Risk stratification scoring used in MM

Answer 74

* IMPEDE Score * SAVED Score

Question 75

IMPEDE Score

Answer 75

**Individual Risk Factors** * Central venous catheter/Tunneled central line +2 * Pelvic, hip, or femur fracture +4 * Obesity (body mass index ≥25) +1 * **Previous VTE +5** **Myeloma Risk Factors** * **Immunomodulatory drug (IMiD) +4** * Erythropoiesis-stimulating agent +1 * Dexamethasone <160 mg/month +2 * **Dexamethasone >160 mg/month +4** * Doxorubicin or multiagent chemotherapy +3 **Negative Factors** * Ethnicity/Race = Asian/Pacific Islander -3 * Existing thromboprophylaxis: prophylactic LMWH (low-molecular-weight heparin) or aspirin -3 * Existing thromboprophylaxis: therapeutic LMWH or warfarin -4

Question 76

SAVED Score

Answer 76

* Surgery within 90 days +2 * Asian race -3 * VTE history +3 * Age ≥80 years +1 * Dexamethasone (regimen dose) * Standard dose (120–160 mg/cycle) +1 * High dose (>160 mg/cycle) +2

Question 77

The highest risk for VTE is in the

Answer 77

First 6 months following new diagnosis of MM

Question 78

# VTE Prophylaxis Recommendations ≤3 Points by IMPEDE Score or <2 Points by SAVED Score

Answer 78

Aspirin 81–325 mg once daily

Question 79

# VTE Prophylaxis Recommendations ≥4 Points by IMPEDE Score or ≥2 SAVED Score

Answer 79

* LMWH (equivalent to enoxaparin 40 mg daily) OR * Rivaroxaban 10 mg daily OR * Apixaban 2.5 mg twice daily OR * Fondaparinux 2.5 mg daily OR * Warfarin (target INR 2.0–3.0) ## Footnote A less common choice of agent includes dalteparin 5,000 units subcutaneously (SC) daily

Question 80

Duration of VTE Prophylaxis

Answer 80

* Indefinite while on myeloma therapy * 3–6 months followed by aspirin (longer periods of anticoagulation may be considered in the presence of additional patient, treatmentspecific, or transient VTE risk factors)

Question 81

Treatment Options for Renal Disease in Myeloma Defined as **serum creatinine >2 mg/dL** or established glomerular filtration rate **(eGFR) < 60 mL/min/1.73 sqm.**

Answer 81

* Pulse dexamethasone * Regimens containing bortezomib and/or daratumumab ## Footnote Can switch to other regimen once renal function has improved or stabilized

Question 82

Lenalidomide Dosing in Patients with Multiple Myeloma Who Have Renal Impairment * CLCr ≥30 mL/min to <60 mL/min * CLCr <30 mL/min (not requiring dialysis) * CLCr <30 mL/min (requiring dialysis)

Answer 82

* CLCr ≥30 mL/min to <60 mL/min: **10 mg every 24 h** * CLCr <30 mL/min (not requiring dialysis): **15 mg every 48 h** * CLCr <30 mL/min (requiring dialysis): **5 mg once daily; on dialysis days, dose should be administered after dialysis**

Question 83

# MONOCLONAL GAMMOPATHY OF RENAL SIGNIFICANCE Renal biopsy recommended if:

Answer 83

* Acute kidney injury (AKI) stage 3 * eGFR <60 mL/min and >2 mL/min per year decline * Proteinuria (>1 g/day) * Albumin:creatinine >30 mg/mmol * Fanconi syndrome ## Footnote The biopsy may be deferred if the eGFR is stable, the urinalysis is normal, or there is no evidence of proteinuria (it is not always light chain proteinuria).

Question 84

# MONOCLONAL GAMMOPATHY OF NEUROLOGICAL SIGNIFICANCE Rule out other causes of neuropathy

Answer 84

* Diabetes * Cobalamin deficiency * Thyroid dysfunction * Lyme disease * HIV infection * Syphilis * Autoimmune disease * Cryoglobulinemia * Evaluation for light chain amyloidosis,, WM or POEMS (POEMS-1), if appropriate

Question 85

# MONOCLONAL GAMMOPATHY OF NEUROLOGICAL SIGNIFICANCE Clinical Findings High suspicion for IgM MGNS (Monoclonal gammopathy of neurological significance) ## Footnote (+) Anti-MAG antibodies

Answer 85

* Sensory predominant * Length dependent * Slow progression (years) * Bilateral and symmetrical * Antibodies present * Demyelination by EMG/NCS OR intermediate suspicion (not high or low suspicion) AND Affecting activities of daily living (ADLs) ## Footnote **Low suspicion** * Motor/pain predominant * Non-length dependent * Rapid progression (weeks to months) * Unilateral/asymmetrical * Antibodies not present * No demyelination by EMG/NCS OR intermediate/high suspicion AND not affecting ADLs

Question 86

# POEMS (POLYNEUROPATHY, ORGANOMEGALY, ENDOCRINOPATHY, MONOCLONAL PROTEIN, Criteria for the Diagnosis of POEMS Syndrome ## Footnote Both of the mandatory major criteria, one of the other three major criteria, and one of the six minor criteria are present

Answer 86

**Mandatory major criteria** * Polyneuropathy (typical demyelinating) * Monoclonal plasma cell-proliferative disorder (almost always **λ**) **Other major criteria (one required)** * Castleman disease * Sclerotic bone lesions * Vascular endothelial growth factor elevation **Minor criteria** * Organomegaly (splenomegaly, hepatomegaly, lymphadenopathy) * Extravascular volume overload (edema, pleural effusion, or ascites) * Endocrinopathy (adrenal, thyroid, pituitary, gonadal, parathyroid, pancreatic) * Skin changes (hyperpigmentation, hypertrichosis, glomeruloid hemangiomata, plethora, acrocyanosis, flushing, white nails) * Papilledema * Thrombocytosis/polycythemia ## Footnote Other signs and symptoms: Clubbing, weight loss, hyperhidrosis, pulmonary hypertension, restrictive lung disease, thrombotic diatheses, diarrhea, low vitamin B12 levels

Question 87

POEMS is believed to be correlated with inflammatory cytokines, such as

Answer 87

Vascular endothelial growth factor (VEGF)

Question 88

# POEMS Treatment for isolated bone lesion (<3 sites) in patients without clonal BMPC

Answer 88

RT

Question 89

# POEMS Induction therapy options for transplant-eligible include:

Answer 89

* Lenalidomide/dexamethasone * Bortezomiba/dexamethasone * Melphalan/dexamethasone * Cyclophosphamide/dexamethasone * Pomalidomide/dexamethasone

Question 90

# POEMS Induction therapy options for transplant-ineligible include:

Answer 90

* Lenalidomide/dexamethasone * Bortezomiba/dexamethasone * Melphalan/dexamethasone * Cyclophosphamide/dexamethasone * Pomalidomide/dexamethasone | Same lang!