Multiple Myeloma

Question 1

Multiple Myeloma Epidemiology

Answer 1

• 3rd most common hematologic malignancy
• More common in African American than White
• More are not dying from the disease itself now

Question 2

MM Patho

Answer 2

• Malignancy of plasma cells resulting in plasma cells that can’t mature into immunoglobulin secreting cells
• Progression from normal plasma cells to MGUS to MM
• Genetic mutations increase with disease progression
• Cells secrete IL-6 which is a growth factor that supports their survival

Question 3

MM Risk Factors

Answer 3

• Ionizing radiation**
• Hereditary
• MGUS
• Environment
• HIV (4.5x risk)

Question 4

MM Screening

Answer 4

• No established guideline

- Careful monitoring for at risk patients

Question 5

MM Signs/Symptoms

Answer 5

• Anemia
• Renal insufficiency
• Bacterial infections
• Oteolytic lesions
• Neurological Symptoms

Question 6

MM Diagnosis

Answer 6

• CBC diff
• Chemistry
• BM aspiration and biopsy
• Skeletal survey and/or PET CT
• Serum and urine electrophoresis (M-protein spike)
• 1 major and 1 minor criteria to meet diagnosis

Question 7

MM Treatment Goals

Answer 7

• Disease control and reversal of disease complications
• Well tolerated therapy
• Decrease risk of early mortality
• Maintain availability of stem cells for potential future transplantation

Question 8

MM Treatment

Answer 8

• Only done for actual multiple myeloma
• Initiating earlier based on progressive disease with end organ damage (CRAB)
• Variety of induction and maintenance therapy regimens

Question 9

CRAB

Answer 9

C - HyperCalcemia
R - Renal Insufficiency
A - Anemia
B - Bone lesions

Question 10

Response Criteria

Answer 10

• PR: partial response, 50% or more decrease in serum M-protein and abnormal bone marrow plasma levels
• VGFR: very good partial response, 90% or more decrease in serum M-protein
• CR - complete response, negative for serum M-protein, disappearance of soft tissue plasmacytomas and <5% abnormal bone marrow plasma cells
• Stringent CR: Cr above + normal free light chain ratio and absence of a clone of abnormal bone marrow plasma cells
• MRD: minimal residual disease on bone marrow samples, additional response criteria with flow cytometry or next-generation sequencing (can identify remaining disease)

Question 11

Thalidomide/Lenalidomide

Answer 11

• Attack multiple targets in microenvironment of myeloma cell
• Causes apoptosis and inhibition of angiogenesis and cytokine circuits
• AE: Neuropathy (T), fatigue (L), thrombosis (L>T)
• Full dose aspirin recommended for patients with mitigate VTE risk

Question 12

Bortezomib/Carfilzomib

Answer 12

• Proteosome Inhibitors

- Can cause neuropathy (B>C), fatigue, cardiac events (C>B), mild-mod myelosuppression

Question 13

CyBorD

Answer 13

• Cyclophosphamide, bortezomib, and dexamethasone
• Primary treatment option for transplant eligible patients with acute renal insufficiency
• If renal fxn improves, can switch to VRd

Question 14

Ineligible BM Transplant

Answer 14

• Give initial chemo
• Treatment based on comorbidities and performance status
• No longer use melphalan due to better benefits of newer agents

Question 15

Renal Adjustments

Answer 15

• None for Carfilzomib, hold or reduce if fxn worsens on drug though
• Lenalidomide: dose adjustments for CrCl <60
• Pomalidomide: no adjustments until CrCl<15, will be removed due to hemodialysis
• Zoledronate: Dose reductions when CrCl < 60

Question 16

Stem Cell Transplantation

Answer 16

• Autologous stem cell transplantation generally with a newer agent is used now
• Delayed transplantation is usually not an option
• Better responses before transplantation have better prognosis for lasting effects
• Tandem stem cell transplant recently shown to have some benefit in studies

Question 17

Relapsed Disease

Answer 17

• Same criteria for treatment as more initiation unless patient’s M-protein is doubling
• Pomalidomide + low dose dexa is used for refractory disease
• Daratumab also approved for refractory disease in patients receiving 3 prior lines of standard therapy
• Dara combined with the pomal + dexa now for those receiving 2 prior standard therapies
• Ixazomib is a possible option too

Question 18

Lytic Bone Lesion Supportive Care

Answer 18

-Pamidronate 90 mg IV
OR
-Zoledronate 4 mg IV 
-Q3-4w x 2 years
-Denosumab for CrCl < 30 or alt to bisphosphonates
-Avoid NSAIDs

Question 19

DVT Prophylaxis

Answer 19

• No or 1 MM risk factor: Aspirin 81-325 mg QD
• IMiD: Aspirin 325 mg QD
• > = 2 risk factors: warfarin or LMWH

**Risk factors described in handout)

Question 20

Infection Prophylaxis

Answer 20

• Most common cause of early death in MM
• Prophylactic antibiotics considered controversial
• Herpes prophylaxis (acyclovir 400mg BID) recommended for all treated with proteasome inhibitors or daratumumab