Multiple Myeloma Flashcards
What are risk factors for developing multiple myeloma
Race (Black)
Age > 65
Gender (male)
Radiation therapy
Obesity
Toxin exposure (pesticides, herbicides)
Genetics (hx of MGUS or first degree relative)
Immune system suppression (on SOT drugs, HIV/AIDS)
What is multiple myeloma? What is the most common Ig found?
A plasma cell disorder where B cells make non-functional antibodies
Most common = IgG
What are the 2 stages before ultimate progression to multiple myeloma?
- MGUS - M protein < 3. Bone plasma cells < 10%. No end organ damage.
- Smoldering MM - M protein > 3. Bence-Jones protein ≥ 500 mg/day. Bone plasma cells 10-59%. No end organ damage.
- MM - Bone marrow plasma cells ≥ 10%. Biopsy proven bony or extramedullary plasmacytoma. End organ damage.
What is the pneumonic for the pathophysiology of MM?
Sixty - ≥60% bone marrow plasma cells
Light chains - uninvolved light chain ratio is ≥ 100
MRI - >1 lesion on MRI ≥5mm
Calcium - SCa > 1 mg/dL above ULN OR >11 mg/dL
Renal - CrCl < 40 mL/min OR SCr > 2 mg/dL
Anemia - Hgb > 2 mg/dL below LLN OR < 10 mg/dL
Bone - ≥1 osteolytic lesion
How does MM infiltration affect bone activity?
Increased osteoclast activity (increased RANK-L)
Increasing focal lesions (lytic lesions)
Anemia (invasion into bone marrow)
Hypercalcemia** (from bone resorption)
How does MM cause renal impairment?
Renal dysfunction is caused by:
- Hypercalcemia from bone invasion
- myeloma cast nephropathy
- concomitant nephrotoxic agents
Leads to decreased erythropoietin/adds to anemia
What kinds of diagnostic workups are required for MM?
Blood tests
24 hr urine test
Bone marrow biopsy
Whole body CT
What is the patient presentation of MM?
Bone pains (back, ribs, hips)
Fracture
Frequent infections
Anemia (SoB, fatigue, palor)
Rare: hyperviscosity and peripheral neuropathy
What is a major supportive care measure for MM? What are some other possible supportive care measures?
Bisphosphinates!
(Or denosumab)
Must get dental clearance before initiating
Recommended use for 2 years
Erythropoietin/transfusions (Anemia)
IVIG (serious recurrent infection)
Acyclovir (for HSV reactivation)
Levofloxacin prophylaxis (newly dx MM)
What are the triplet and quadruplet regimens? (MM)
Gold standard - triplet regimen RVd
- Revlimid (lenalidomide), Velcade (bortezomib), dexamethasone
Some pts may benefit from quadruplet regimen Dar-RVd
- Daratumumab, Revlimid (lenalidomide), Velcade (bortezomib), dexamethasone
What kind of transplant is preferred after chemo in MM? How many cells should be collected? What are some considerations?
Preferred - autologous stem cell transplant (self-cells), allogenic has high toxicity
Collect enough cells for 2 transplants
Consider: age, renal/hepatic/cardica function, performance status, caregiver support
What are some premedication and post medication medications for DARATUMUMAB? (MM)
Premed:
Dexamethasone/MPS
APAP
Benadryl
Montelukast for first dose
Postmed:
MPS
What are some side effects of Daratumumab? (MM)
Infusion rx
Herpes zoster reactivation
Hepatitis B reactivation
What is the MOA of Daratumumab? (MM)
Anti-CD38 kappa human mAb
What is the MOA of Bortezomib? (MM)
Proteasome inhibitor = causes major apoptosis!
What formulation of Bortezomib is preferred and why?
SQ
IV causes terrible peripheral neuropathy!
What are some AEs of Bortezomib? (MM)
Herpes zoster reactivation
Thrombocytopenia
Peripheral neuropathy (IV bortezomib > SQ Bortezomib > ixazomib»_space; carfilzomib)
What is the MOA for Lenalidomide? (MM)
Immunomodulator drug (IMiD)
Anti-angiogenic (like VEGFi)
Upregulation of pro-apoptotic factors/enhanced recruitment of T-cells and NK-cells
What is the route of admin for Lenalidomide and what is the admin schedule? (MM)
Oral!
Take days 1-21 of the 28 day schedule
OR
Days 1-14 of a 21 day schedule
What are some AEs of Lenalidomide? (MM)
BIRTH DEFECTS [REMS program]
Hematologic toxicity
Thrombosis
Somnolence
Increased secondary malignancy
Rash + skin toxicity
Diarrhea
Peripheral neuropathy
What is a special program Lenalidomide patients must be enrolled in? What do they have to do to qualify for the drug?
REMS program
Confidential surveys must be completed monthly for females who can get pregnant and males
OR
Every 6 months for females who cannot get pregnant
MUST USE highly effective birth control + barrier method
How should we counsel couples who cannot get pregnant and want to use Lenalidomide?
- Many different people could be exposed to the medications
Wash hands/use gloves, store in original packaging, proper disposal
What increases risk of thrombosis in MM patients? What can decrease the risk?
INCREASED risk:
Prior VTE
High dose steroids
Obesity
Catheters
Fractures
Lenalidomide use
DECREASED risk:
Asian/Pacific islander
What anticoagulation prophylaxis should MM patients get if they are already on pre-existing anticoagulation?
Continue prescribed anticoagulation in most cases (Eliquis, enoxaparin, etc)
DO NOT decrease intensity!
What anticoagulation prophylaxis should MM patients get if they are on lenalidomide after a partial response with no other risk factors?
Aspirin 81 mg
What are side effects of dexamethasone? (MM)
• Insomnia
• Mood changes
• Increased appetite
• GI upset/reflux
• Hyperglycemia
• Edema
• Weight gain
• Hypertension
MM patients can have varied chemo regimens based on what they have previously received. Elotuzumab is one of these; what is the MOA?
Humanized IgG antiAb
Directly activates NK cells
MM patients can have varied chemo regimens based on what they have previously received. Elotuzumab is one of these; what are the medications used for premedication?
APAP
Benadryl
Famotidine
Dexamethasone (3-24 hrs before, then immediately before)
MM patients can have varied chemo regimens based on what they have previously received. Elotuzumab is one of these; what are some AEs?
Infusion reactions
Thrombocytopenia
Herpes Zoster reactivation
What are the Bispecific T-cell Engagers (BiTEs)? What is their MOA?
Talquetamab
Teclistamab
Elranatamab
MOA - Targets one tumor antigen and one immune-related molecule (or 2 tumor antigens/immune-related molecules)
Patients on the BiTEs drugs in MM are required to enter a REMS program. What is required for these patients to receive their drug?
Verify prescribers have completed training, forms etc. and that patients are being counseled on the side effects
What are two MAJOR side effects of all the BiTEs drugs (MM)?
Cytokine Release Syndrome
Immune Effector Cell-Associated Neurotoxicity
Describe Cytokine Release Syndrome in BiTEs patients (MM). What is the presentation?
Increased cytokines due to T-cell activation which causes a systemic inflammatory response
Presentation: Fever, hypotension, hypoxia
Describe Immune Effector Cell-Activated Neurotoxicity in BiTEs patients (MM). What is the presentation? What can it be treated with?
Disruption of the blood brain barrier and increased cytokines in the CSF.
Worst presentation: stupor/unarousable, prolonged, seizures, focal edema, motor weakness
Treatment: antiepileptics, steroids, supportive
Talquetamab has significantly more AEs than the other BiTEs. What are they?
UNIQUE to drug:
Skin AE (eczema, fissures, hyperpigmentation, lesions/ulcers)
Nail AE (nail bed disorder, hypertrophy, ridging, onycholysis)
Rash AE (dermatitis, rash)
Oral AE (dry mouth and food tastes BAD)
Weight Loss
ALL BiTEs:
Cytopenia
Cytokine Rekease Syndrome/Immune Effector Cell-Associated Neurotoxicity
[many people d/c because of AEs]
What are the AEs of BiTEs Elranatamab and Teclistamab? (MM)
Cytopenia
Cytokine Rekease Syndrome
Immune Effector Cell-Associated Neurotoxicity
