Flashcards in 18 Multiple Myeloma Kasravi Deck (49):
What is multiple myeloma?
Clonal B-cell malignancy of slowly proliferating plasma cells within the bone marrow. Invasion of bones --> lesions. Produce monoclonal protein (M protein)
What are the clinical manifestations of Multiple Myeloma?
Bone lesions and pain. Infection. Renal insufficiency. Anemia. Bleeding. Hyperviscosity syndrome. Neurological symptoms. Secondary leukemia and MDS
What is the MOST COMMON symptom of Multiple myeloma?
Bone Pain. Bone lesion (activation of osteoclasts (response to OAF; leads to hypercalcemia), Osteoporosis/Osteopenia, Lytic (mobilization of calcium from bone --> hypercalcemia), Palpable (skull, clavicles, sternum, spinal cord compression))
What are the causes of infection in multiple myeloma?
Diffuse hypogammaglobulinemia. Poor antibody response to polysaccharide antigens (bacterial cell wall). T-cell function remains normal. Granulocytes function and migration decreased
What does Hypercalcemia lead to in multiple myeloma?
Renal insufficiency. Tubular damage associated with excretion of light chains. GFR remains normal. ARF if patient becomes dehydrated
How is the multiple myeloma diagnosis made?
Classic triad: Clonal bone marrow plasma cells or plasmacytoma, Serum and/or urine M-component, Related organ or tissue impairment (hypercalcemia, renal insufficiency, anemia, lytic bone lesions)
What is done for maintenance post transplant?
Low dose Thalidomide + Prednisone. Lenalidomide. Steroids
What is done for Salvage Therapy?
Repeat primary induction if relapse > 6 months. Bortezomib based regimen. Bendamustine (Treanda). Carfilzomib (Kyprolis)
What is Melphalan (Alkeran)?
Alkylating agent. Comes in 2mg tablet or 50mg powder of injection
What are the ADRs with Melphalan (Alkeran)?
Myelosuppression (leukopenia, thrombocytopenia). N/V/D, mucositis (dose dependent). Hypersensitivity - 10% IV
What is the emetogencitiy like for Melphalan (Alkeran)?
IV: Very high. Oral: Very low
What are the DDIs with Melphalan (Alkeran)?
Cimetidine and other H2 antagonists. Take oral form on EMPTY stomach
What are the ADRs with Prednisone?
Insomnia (take dose QAM). Hyperglycemia. Increased appetite, indigestion, gastritis
What are the dosage forms for Prednisone?
Oral solution: 1mg/mL. Concentrate oral solution: 5mg/mL. Tablet: 1, 2.5, 5, 10, 20, 50mg. Often dosed high for this type of cancer. Take with food
*What is Thalidomide (Thalomid)?
Immunosuppressant, TNF-a blocker
What is the FDA indication for Thalidomide (Thalomid)?
Treatment of leprosy, treatment of Multiple Myeloma (with Decadron)
What is the MOA of Thalidomide (Thalomid)?
Mode of action for immunosuppression is inclear. Inhibition of neutrophil chemotaxis and decreased monocyte phagocytosis
*What is the System for Thalidomide Education and Prescribing Safety (STEPS)?
Must be dispensed in manufacturer packaging. Maximum dispense: 4-week supply. Blister packs should be dispensed intact. Prescriptions must be filled within 7 days. Written Rx required for each fill; new Rx dispense once < 7 day supply remain. Must provide FDA-approved medication guide each time
*What is the dosing of Thalidomide (Thalomid) like?
50mg, 100mg, 200mg capsules. Take 1hr after evening meal. Taken at bedtime to minimize sedative effect
What are the COMMON ADRs with Thalidomide (Thalomid)?
Peripheral edema, rash, hypocalcemia, constipation, nausea, neutropenia, confusion, sedation
What are the SERIOUS ADRs with Thalidomide (Thalomid)?
SJS, TEN, neutropenia, peripheral neuropathy, thrombotic disorders
What is the BBW with Thalidomide (Thalomid)?
Severe life-threatening birth defects, STEPS program, effective contraception (males and females), increase risk of VTE in MM. Pregnancy category X
What are the DDIs with Thalidomide (Thalomid)?
Alcohol - may enhance sedation. Anti-TNF agents - avoid use, increase risk of infections. Live vaccines
What are the monitoring parameters for Thalidomide (Thalomid)?
CBC with diff monthly for first 3 months, then periodically. S/Sx of VTE, neuropathy. Women of childbearing potential (pregnancy testing is required within 24 hours of initiation of therapy, weekly during the first 4 weeks, then every 4 weeks in women with regular menstrual cycles or every 2 weeks in women with irregular menstrual cycles)
What is Lenalidomide (Revlimid) approved for?
Treatment of MM (2nd line), MDS. Unlabeled use as treatment of MM 1st line
What are the restrictions with Lenalidomide (Revlimid)?
Restricted distribution program called RevAssist. Physicians, pharmacies, and patients must be registered. Maximum 28 day supply may be dispensed. New Rx required each time. Pregnancy testing is required for females of childbearing potential. Must provide FDA-approved medication guide each time
What are the ADRs with Lenalidomide (Revlimid)?
Myelosuppression (neutropenia, thrombocytopenia) 80% of patients. Increase risk of thrombosis (DVT, PE). Peripheral edema, dizziness, vertigo, chills, malaise. N/V/D, rash, arthralgia, muscle cramps, fatigue, less neuropathy than Thalomid
What is the emetogenicity with Lenalidomide (Revlimid)?
What does Lenalidomide (Revlimid) need to be dose adjusted?
Dose adjustment for thrombocytopenia and neutropenia, renal function
What are the DDIs with Lenalidomide (Revlimid)?
Anti-TNF agents - avoid use, increase risk of infections. Live vaccines
What is the BBW with Lenalidomide (Revlimid)?
Severe birth defects (category X), hematological toxicity, DVT/PE
What are the monitoring parameters with Lenalidomide (Revlimid)?
CBC w/ diff weekly for first 8 weeks, then monthly. CMP (SCr, LFT, TFT). S/Sx of VTE. Women of childbearing potential (pregnancy test 10-14 days and 24 hours prior to initiating therapy, then every 2-4 weeks through 4 weeks after therapy discontinued)
What is Bortezomib (Velcade) indicated for?
1st line treatment of MM, 2nd line mantle cell lymphoma
What is the MOA of Bortezomib (Velcade)?
Proteasome inhibitor (activation of signaling cascades, cell-cycle arrest and apoptosis)
When does Bortezomib (Velcade) need to be dose adjusted?
For toxicity. Hematological (thrombocytopenia), peripheral neuropathy, neuropathic pain
What is the emetogenecity of Bortezomib (Velcade)?
What are the ADRs with Bortezomib (Velcade)?
Myelosuppression. Neuromuscular and skeletal
What are the DDIs like with Bortezomib (Velcade)?
A LOT. Moderate 2C19 inhibitor (may decrease efficacy of Plavix). Green tea (diminishes anti-neoplastic efficacy of Bortezomib (Velcade)
What is Carfilzomib (Kyprolis) indicated for?
3rd line treatment of MM (including Bortezomib)
What is the MOA of Carfilzomib (Kyprolis)?
2nd generation Proteasome Inhibitor (highly selective and irreversible)
When does Carfilzomib (Kyprolis) need to be dose adjusted?
For toxicity. Hematological (thrombocytopenia), cardiac toxicity, pulmonary HTN, hepatic toxicity
What is the emetogenecity of Carfilzomib (Kyprolis)?
What is some general info on Carfilzomib (Kyprolis)?
Less neurotoxicity, even with subcut Bortezomib. Dexamethasone premedication to prevent infusion reaction cycle 1 and cycle 1 of dose escalation. Adequate hydration to prevent renal toxicity and TLS
What are the two choices to help manage Hypercalcemia?
Bisphosphonates: Zoledronic Acid (Zometa) or Pamidronate (Aredia)
How is Zoledronic Acid (Zometa) dosed in the treatment of hypercalcemia of malignancy (corrected serum calcium > 12)?
4mg IV once, wait at least 7 days prior to re-treatment
How does Zoledronic Acid (Zometa) work?
Decreases serum calcium and phosphorous, increase their elimination
What is a warning with Zoledronic Acid (Zometa)?
Osteonecrosis of jaw - dental exam prior to start of therapy. Avoid invasive dental procedures
What are the ADRs with Zoledronic Acid (Zometa)?
Myalgia, arthralgia, fatigue, decrease phos, K, Ca