CC July 2016 Multiple myeloma

echoecho's version from 2016-10-09 02:54


Question Answer
Define multiple myeloma (MM)?as neoplastic proliferation of a malignant clone of plasma cells that produce a monoclonal immunoglobulin (M protein)
IgG accounts for ___% of myelomas and IgA accounts for ___%?52; 21
Kappa or lambda light chains only are found in ____% of patients, while IgM, IgD and biclonal immunoglobulins are quite _____?18; rare
___% of myelomas are nonsecreatory (no monoclonal proteinin serum or urine)?2
*** List the other types of plasma cell dyscrasias?1) localized extra-medullary plasmacytomas 2) monoclonal gammopathy of undetermined significance (MGUS) 3) smoldering myeloma (SMM)
Regarding localized extra-medullary plasmacytomas without evidence of disseminated myeloma are treated how? A solitary plasmacytoma of bone carries a 50-60% chance of eventual ____ even with a negative bone marrow evaluation and SPEP?1) local radiation or surgery 2) multiple myeloma
*** Regarding monoclonal gammopathy of undetermined significance (MGUS), what does this refer to?a small immunoglobulin spike of < 3 g/dL of IgG or IgA
*** The above patients have < ____% plasma cells in their bone marrow and do not have signs or symptoms of MM. Give the CRAB criteria?1) 10 2) normal Calcium, Renal function, no Anemia and no lytic Bone lesions
*** Patients with MGUS are followed every ___ to ___ months with 1% per year developing active myeloma. Why is this a significant problem in the elderly?1) 6; 12 2) because there is up to 10% of people > 80 years of age that will have MGUS
Regarding smoldering myeloma (SMM), what does this refer to?1) patients who have > 10% plasma cells in the marrow and /or an M spike > 3 g/dL for IgG or IgA but do not have any of the CRAB criteria to dx active MM
How is smoldering myeloma (SMM) followed and why?followed closely because of 10% yearly risk of progressing to active MM so that 1/2 of these patients undergo treatment for MM within 5 years of dx
After 15 years, however, ____% of patients with smoldering myeloma still have not needed treatment?25
Trials are under way treating high risk SMM, define high risk SMM; to determine whether early therapy will impact favorably on survival and quality of life?1) > 60% plasma cells in bone marrow 2) positron emission tomography (PET) positive bone lesions
Define MM?1) an incurable malignancy of plasma cells 2) most commonly with bone destruction causing osteolytic lesions and fracture
In 2015, it was estimated that in the US, there would be ______ new cases of MM with 11,240 deaths?26,850
MM represents ___% of all new cancer cases and 1.9% of all cancer deaths?1.6
Presently, how many people live with myeloma in the US?> 90,000
What is the average age at dx? What is the gender predominance?1) 69 2) 1.4: 1 (male predominance)
Only what % of MM patiens are < 45 year old?4
The incidence of MM varies by ethnicity with the incidence in AA ___ to ___ times that in caucasians?2; 3
The risk in what two ethnic groups is lower?Japanese and Mexicans
Is there evidence that familial preisposition may increase the risk of developing MM?yes
There is a ____ fold increase risk of active MM in persons w/ a first degree relative with MM?3.7
What three reasons have led to an overall improvement in survival wtih myeloma to an average of 7 years?1) improvement in dx 2) stratification of risk 3) new therapies
What % of patients live beyond 10 years?30%
List the clinical presentations reflecting the spectrum of problems MM causes?1) anemia (75%) 2) bone pain (60%) 3) elevated creatinine (50%) 4) fatigue and weakness (30%) 5) hypercalcemia (30%) 6) weight loss (25%) 7) LAD, peripheral neuropathy, spinal cord compression, hepatosplenomegaly (5%)
Patients with MM have inhibited response to infection, why?because they have suppressed production of normal immunoglobulins as well as impaired lymphocyte function, inhibiting response to infection
Acute infection is the initial presentation for 8-10% of patients with MM and is usually what 2 types of infections?1) pulmonary OR 2) UTI
What is the most common organisms associated with MM-related infection?1) pneumococcus 2) Haemophilus influenza 3) E. coli
*** The initial dx of MM is straightforward, explain?SPEP, immunofixation and free light chain ratio will determine the immunoglobulin and/or light chain-associated with monoclonal plasma cell proliferation
*** The presence of any of the CRAB criteria confirms what?active myeloma and treatment is indicated
*** Once dx is made, what exam must be done and why?a bone marrow must be done to determine the % of plasma cells in the marrow (diagnostic criterion, > 10%) and for cyotogenetics and mutation analysis by fluorescent in situ hybridization (FISH) that will help stratify patients into low, intermediate and high-risk MM
List the risk stratification for MM?1) Frequency = (high risk 15-20%; intermediate risk 20-25%; standard risk 60%) 2) FISH findings = (high risk = 17p13 deletion, T (14;16), T (14;20), 1p deletion; intermediate risk = T(4;14); deletion 13 q and hypodiploidy by conventional karyotyping); standard risk = hyperdiploidy (trisomies); T (11;14), T (6;14) 3) other characteristics = (high risk = LDH > 2 times normal and features of primary plasma cell leukemia)
What radiographic study is more accurate than a nuclear bone scan for delineating the extent of osteolytic bone metastasis?a myeloma radiographic skeletal survey
What 2 other imaging studies are being used more often to clarify the extent of disease and need for treatment and can be helpful in patients with bone pain and negative radiographs and are part of the evaluation of a person with smoldering myeloma or solitary plasmacytoma?1) PET/CT scan 2) MRI
What lab test is indicated if the M-protein level > 5 g/dL?serum viscosity
Is bone scan a part of the evaluation of MM?no
What disease is a common and difficult problem in MM?renal disease
What i the most common cause of renal imapirment occurring in 50-6% of patients with elevated creatinine?myeloma cast nephropthy caused by preciptation of light chains in the urine (myeloma kidney) is a common cause
Rapid therapy with what can preserve adequate renal function (although major improvement when creatinine > 6 mg/dL is uncommon?bortezomib (Velcade) - based treatment, hydration and control of calcium
List other causes of renal impairment?1) amyloidosis 2) monoclonal immunoglobulin deposition disease
What other modalities can further compromise reinal function?1) radiocontrast administration 2) NSAIDS 3) biphosphonate therapy
After the dx of MM is made, what is needed?staging
The International Staging System (ISS) uses what levels to determine stage? 1) beta-2 microalbumin 2) albumin levels
Question Answer
List the stage, findings and median survival in the International Staging System?1) stage 1 (beta-2-microglobulin < 3.5 mg/L and serum albumin > 3.5 g/dL = median survival 65 months) 2) stage 2 (neither stage I or III = 45 months) 3) stage 3 (beta 2 microglobulin > 5.5 mg/L = 30 months)
A revision of ISS adds what 2 levels (components of risk stratification) to determine stage?1) FISH cytogenetics 2) LDH
What findings of LDH, cytogenetics and FISH studies will impact overall survival negatively?1) elevated LDH 2) poor prognostic cytogenetics 3) poor FISH studies
Initial treatment for MM is based on what?1) staging system 2) prognostic molecular features 3) patient's co-morbidities 4) age 5) whether the patient is a transplant candidate or not
List facts that would make a patient ineligible for transplant?1) age > 77 years 2) direct bilirubin > 2 mg/dL 3) poor performance status 4) New York Heart Association functional classes III and IV
For low-risk elderly patients, what treatment is effective with durable remissions?1) a combination of lenalidomide (Revlimid), an immune modulating drug AND 2) low dose dexamethasone (Decadron) 40 mg orally once weekly is effective with durable remissions
*** Medium and high-risk patients are treated with what 3-drug regimen? lenalidomide 2) bortezomib (Velcade) 3) dexamethasone OR cyclophosphamide (Cytoxan), bortezomib and dexamethasone
*** Generally after 3-6 cycles of therapy, eligible patients undergo what? Comment on tolerability to this and treatment-related death rate?1)an autologous stem cell transplant (ASCT) using high-dose IV melphalan (generic Alkeran) 2) generally well tolerated by fit patients with a 1-2% treatment-related death rate but an improved survival of 1.5-2 years compared to non-transplant patient
The vast majority of patients who have significant responses to treatment w/ or w/o an ASCT are put on what? This strategy has been shown to improve what? 1) maintenance therapy (lower dose lenalidomide or bortezomib) until there is evidence of progressive disease. 2) improve both progression-free and overall survival
Why are allogenic bone marrow transplants seldom done in MM patients?there is a high treatment-related mortality (>40%) and lack of long-term disease control in those who survive
What are the options when patients relapse?1) chemotherapy 2) histone deacetylase (HDAC) inhibitors (panobinostat (Faryak), new generation immune-modulating drugs (pomalidomide (Pomalyst) and proteasome inhibitors (carfilzomib (Kyprolis)
List the 2 monoclonal antibodies with different mechanisms of action that the FDA has approved for use in MM?1) Daratumumab (Darzalex) is directed to CD38 protein on the myloma cell membrane and works in the same way rituximab (Rituxan) does in lymphoma, synergizing with chemotherapy. 2) Elotuzumab (Empliciti) is an immune-stimulating agent targeting SLAMF7 that activates lymphocytic signaling and, in combination with lenalidomide and dexamethasone, delays progression by more than 6 months
Comment on Zoledronic acid (Reclast) in treatment of MM and list the benefits of the medication?1) it is a bisphosphonate that causes apoptosis of osteoclasts and decreases bone reabsorption 2) this leads to a reduction in skeletal-related events (bone fracture, need for radiation, spinal cord compresion and hypercalcemia and clearly improves quality of life
Why should low risk patients be on low-dose aspirin if taking immune modulation drugs. What should higher risk patients be on?1) because immune-modulation drugs are thrombophilic 2) on more significant anticoagulation
What are the disadvantage of bortezomib use? Because of this what is the prophylaxis?1) associated with an increase in herpes zoster 2) prophylaxis with acyclovir (Zovirax) 400 mg BID
*** SUMMARY = Describe multiple myeloma?1) it is a plasma cell dyscrasia 2) has significant morbidity and mortality associated with anemia, osteolytic bone lesions and fracture, fatigue and renal dysfunction
*** SUMMARY = Dx is based on what?1) abnormal SPEP identifying immunoglobulins, most commonly IgG
*** SUMMARY = Is there evidence of a familial disposition?yes
*** SUMMARY = What three modalities influence risk and treatment options?1) specific chromosomal deletions 2) translocations 3) hyperploidy
*** SUMMARY = Treatment of multiple myeloma?1) combination therapy with immune-modulating drugs and sterois 2) autologous stem cell transplantations