Living Well With Myeloma: Making Sense of Tests and Results

Living Well With Myeloma: Making Sense of Tests and Results


good evening everyone and welcome to the
International Myeloma Foundation’s webinar making sense of myeloma tests
and results I’m Robin Tuohy senior director of support groups for the
International Myeloma Foundation tonight’s program is part of the IMF’s
Living Well with Myeloma series which is designed to cover all the important and
most up-to-date information regarding myeloma to help you live well I’d like
to thank our sponsors for their support of tonight’s call Celgene, Janssen
pharmaceuticals and Takeda Oncology it’s now my pleasure to introduce tonight’s
speakers Debbie Birns is the IMF medical editor she started as the IMF’s first
official hotline specialist and she is now the IMF’s medical editor overseeing
and writing the scientific content of Myeloma Today and composing many other
IMF publications including the booklets in the Understanding Series we’re also
very pleased tonight to have a special guest speaker Dr. Rafat Abonour from
Indiana University Simon Cancer Center Dr. Abonour is a consultant for the IMF
and he is also part of the IMF’s International Myeloma Working Group and
he will be available to take your questions tonight and it’s now my
pleasure turn tonight’s call over to Debbie Birns and
Dr. Abonour Debbie Thank You Robin and thank you Dr. Abonour for helping out
this is going to be a quick tour through a lot of tests so hang on tight the
information is designed for patients and caregivers to help them understand why
certain tests are done and what they tell us
I’ll begin with some general precautions and suggestions first of all what can
tests tell us well for one thing a diagnosis is this myeloma or a precursor
to myeloma either monoclonal gammopathy of
undetermined significance better known as MGUS or smoldering myeloma
abbreviated SMM what is the risk of progression to myeloma if you have one
of the precursors to myeloma what is your risk of actually progressing to
active myeloma what are the type and stage of the myeloma the type of myeloma
depends on the type of heavy chain and light chain antibody or immunoglobulin
that the myeloma cells are secreting stage tells us about disease prognosis
how will the myeloma behaves based on the presence absence or amount of
certain measurable factors are there genetic risk factors one of these
factors to assess risk is the presence or absence of genetic mutations in the
myeloma cells that can influence disease behavior is the treatment working is
your myeloma worse than better than or the same as where you were when you
started treatment our treatments causing side effects for example we can often
see the effects of a treatment if it lowers the blood cell counts and finally
how deep is the response to therapy for example are the bones and kidneys
improving are there a normal number of plasma cells in the bone marrow our
immunoglobulin levels back to normal immunoglobulin by the way is medical
speak for antibody no single test tells the whole story each test is a piece of
a puzzle that must be assembled to understand what’s going on don’t compare
test results with other patients myeloma is unique in every patient two patients
may for example have the same type and amount of monoclonal protein yet one of
them may be very ill while the other has minimal disease and is doing very well
many of you can go online to see your test results make sure you’re looking at
the test your oncologist ordered this webinar should help you identify
which tests are for assessing myeloma and which tests may be for other
conditions because they won’t be mentioned always discuss your test
results with the doctor who is treating you
the oncologist who’s treating your myeloma will be able to put all the
puzzle pieces together and put everything in context for you because he
or she knows all the details about your myeloma in your treatment history
patterns of results viewed over time are more meaningful than any single test
result in isolation always request or print out and save copies of your test
results you should bring a summary of your test results with you when you and
your oncologist are figuring out what to do next or when you see another doctor
for a second opinion for some patients certain tests are more important than
others myeloma is different in every patient which tests tell you most about
your myeloma may depend on certain features of your disease more caveats
normal a values vary from lab to lab they are given as a range from the lower
limit of normal to do.you upper limit of normal in parentheses usually on your
lab report next to your result this gives you a way to compare your results
with what is the expected range for healthy individuals test results can
also vary from lab to lab variations and results from different labs can be
caused by differences in lab equipment or in human interpretation for tests
that aren’t fully automated factors having nothing to do with myeloma that
can affect test results include medicines or supplements that you take
caffeinated beverages or alcohol you may have consumed beef consumption stress or
strenuous exercise be sure to find out if there are any restrictions on diet or
activity before you go to the web the units on
lab values may also vary from lab to lab if there’s a big difference between your
current test and your last test make sure you check the units on your lab
results to see if they’re the same as your last test sometimes doctors change
labs or use more than one lab there’s no time like the present to become
comfortable with that good old decimal system if you’re not already comfortable
6 grams of monoclonal protein equals 6,000 milligrams a thousandth of
a gram one liter equals 10 deciliters you need to be able to do the math and
move your decimal points correctly if the unit’s switch because this is so
important I’ll say once again that you must get and keep copies of your test
results you’ll want to keep the copies of your test results to see patterns
over time save these results on your computer and copy them onto a flash
drive there are three major types of tests for myeloma listed on this slide
lab tests to assess substances in the blood and/or urine tests done on bone
marrow samples and imaging studies I’ve broken down the tests that’s in the top
category blood and urine which are very numerous into smaller groups by
categories tests that assess kidney function tests that assess blood
proteins other than monoclonal protein and other substances in the blood and a
very important group of tests that are used to assess monoclonal protein our
first puzzle piece is a very common test it’s used as part of a healthy checkup
with your primary care physician and is used throughout the myeloma disease
course it’s the Complete Blood Count or CBC the graphic here shows
you a typical lab report for the CBC the CBC gives us information about the
number and characteristics of red blood cells which carry oxygen to our tissues
and organ’s white blood cells which make up our immune system and platelets
which clot the blood after an injury and note about units I’ve provided the Mayo
laboratory lab unit for each test I will discuss this evening you can see on this
test right next to RBC WBC and platelets it has a number for RBC it’s ten to the
twelfth per liter or billions of cells per liter of blood so for every test I’m
going to talk about tonight there are units listed that are used by the Mayo
lab the Mayo lab is an international reference laboratory any doctor around
the world can send samples there for analysis your lab may not use the Mayo
lab units in fact the sample CBC report I put on this slide doesn’t use Mayo
units you can see for white blood cells if you look across the line the very
right side it says four point five to eleven point 0 which is the
normal range lower limit of normal to upper limit of normal and then it says K
/ul which stands for thousands per microliter the u looks like the Greek
letter mu so pretty substituted because they don’t have Greek on their computer
but it is equivalent to the Mayo units just expressed differently the four
columns on this lab report are from left to right first column the cell types and
characteristics the patient’s result in numbers third column an indication of
whether the result is L for low, left blank for normal, or H for high compared
to those normal ranges and for the range of normal values from the
lower limit of normal to the higher limit of normal with the units used for
each test to understand why the CBC is important you have to understand a bit
about myeloma my apologies to those of you who already know this but please
bear with me on behalf of those who don’t myeloma grows in the bone marrow
where our blood cells are made too many myeloma cells can lower the blood cell counts if there are too few red blood
cells than low hemoglobin also know known as anemia results anemia is often
an early sign of myeloma and is the “A” in the diagnostic CRAB criteria for
myeloma myeloma is actually a cancer of white blood cells of a certain white
blood cell an immune system cell called a B lymphocyte or B-cell that develops
into a plasma cell the plasma cells job is to make antibodies against substances
that invade our bodies when there are cancerous plasma cells we call them
myeloma cells in the bone marrow the whole immune system goes out of whack
lowering the immune response low levels of white blood cells called neutrophils
which targets bacteria and fungi can lead to increased risk and infection low
levels of white blood cells called lymphocytes can lead to reduced ability
to make antibodies and kill ourselves to target other foreign substances in the
body many treatments for myeloma can also lower neutrophils and lymphocytes
see my little down arrows there I hope you do they’re showing up kind of funny
on the slide but they are supposed to be down arrows the iMids, Revlimid, pomalyst
and thalidomide immunomodulatory drugs iMids for short can lower the neutrophil
count while steroids like dexamethasone can lower the lymphocyte count the
treatments velcade kyprolis and ninlaro all of which are in the drug class called proteasome inhibitors can lower the
platelet count our next puzzle pieces are blood tests in the metabolic panel
that assess kidney function kidneys can be damaged by light-chain monoclonal
protein or by high blood calcium levels that results from the breakdown of bones
kidney related and medical speak is third renal tests of kidney function
established the “R” for renal in the CRAB diagnostic criteria serum is the clear
part of the blood when all the blood cells are taken out creatinine is the
waste product from normal muscle breakdown when kidney function is
impaired the kidneys cannot rid the body efficiently of creatinine and it’s level
builds up in the blood creatinine clearance testing uses both a blood
sample and urine from your beloved 24-hour urine collection it is more
accurate than serum creatinine measurement and is the International
Myeloma Working Group or IMWG’s preferred test for establishing the “R”
part of the CRAB criteria remember that while the level of creatinine and
the blood increases with kidney damage the clearance of creatinine from the
body is decreased with kidney damage the glomeruli are the basic filtration units
of the kidney the IMWG diagnostic criteria use estimated glomerular
filtration rate or eGFR for short to determine the “R” for renal in the CRAB
criteria rather than serum creatinine level because it is a more reliable
measure it’s calculated automatically as part of the creatinine clearance test
you’ll notice that it is expressed as an estimation of how many milliliters of
creatinine are cleared per minute per square meter of your body mass
blood urea nitrogen our BUN or B-U-N is a measurement of the waste product that
accumulates in the blood when the body breaks down proteins the amount of blood
urea nitrogen increases when the kidneys or liver are damaged our next series of
puzzle pieces are tests used to measure certain proteins and other substances in
the blood that are part of the blood chemistry panel also called the
metabolic panel the panel of tests like the CBC is also part of a basic medical
exam so while these tests can tell us about how the myeloma is behaving they
are not specific for myeloma and are also used for other medical conditions elevated blood calcium or hypercalcemia
is the “C” in the CRAB diagnostic criteria calcium is released into the
blood by bone breakdown hypercalcemia can cause kidney damage bisphosphonates
therapy with zometa to prevent bone breakdown is also a treatment for
hypercalcemia the total protein test measures all the proteins in the blood
which fall into one of two types either globulin or albumen globulin is antibody
protein so it is therefore increased when myeloma cells are making monoclonal
protein which is a globulin albumin is made in the liver and is excreted by the
kidneys changes in the amount of albumin are not related to myeloma but can
indicate liver or kidney disease albumin is the most abundant protein in the
blood neither serum beta-2 microglobulin nor lactate dehydrogenase level is a
test used only for myeloma but high sB2M is is but sB2M is elevated when
myeloma is act high sB2M indicates more active and
aggressive disease the same is true for LDH both sB2M and LDH are used in
the staging system for myeloma sB2M is in the International Staging
System or ISS and LDH is part of the revised ISS or R-ISS elevated
c-reactive protein is a marker of inflammation CRP testing is probably
used most commonly in the context of heart disease but many diseases other
than heart disease can cause increased CRP including cancer infection and
autoimmune conditions such as rheumatoid arthritis lupus and irritable bowel
syndrome in a myeloma patient increased CRP can signal active disease CRP is
produced in the liver in response to inflammation our next test is used to
measure blood glucose or blood sugar the level of blood glucose should be
monitored carefully in all patients taking a steroid such as dexamethasone
which can raise the blood glucose levels our next group of blood and urine tests
are very important because they are used specifically for assessing myeloma they
all measure the output of myeloma cells monoclonal protein in the blood and/or
urine serum protein electrophoresis known by its acronym SPEP is a test
that separates all the proteins in the blood according to their electrical
charge urine protein electrophoresis or UPEP does the same
thing for proteins in the urine the upper graph on this slide represents
events a normal SPEP result it shows a peak in the measurement of albumin which
you’ll remember is the most plentiful protein in the blood and lower levels
the other proteins grouped into areas labeled alpha 1 and 2, beta with two
bumps also known as 1 and 2 that aren’t labeled here and gamma which is
where the antibody proteins including those made by myeloma cells would lie on
the graph the lower graph represents the results for a patient with myeloma in
addition to the spike for albumin we see another tall spike indicated by the red
arrow in the gamma region of the graph the area under that spike or curve can
be measured the pathologist measures the area under that curve and then subtracts
the normal level of gamma gamma globulin from that total and that is your level
of monoclonal protein also known as M-protein made by the myeloma cells SPEP and UPEP tell us how much monoclonal protein there is but not the
type remember that monoclonal protein is the output of myeloma cells in most
people with myeloma but every person’s myeloma is unique to them the output can
vary in amount from patient to patient and can vary in how that amount relates
to the behavior of the myeloma SPEP and UPEP are an indirect measurement of
how the myeloma cells are behaving and not every person’s myeloma cells behave
in the same way or reproduce at the same rate some other issues with SPEP
immunoglobulin a or IgA type myeloma monoclonal protein does not separate out
in the gamma region of the graph but can get stuck with the beta or even alpha
proteins patients with IgA heavy chain myeloma usually do better using a
different test to assess how much IgA they’re making another issue is that
treatment with Darzalex also known by its generic name daratumumab can very
slightly increase the m-spike but only in patients who have IgG Kappa myeloma
the Darzalex is made out of IgG Kappa monoclonal protein this is only a problem for patients with IgG myeloma who are being assessed for
complete response after treatment with Darzalex an experienced pathologist
is usually able to determine if this small amount of immunoglobulin protein
is the Darzalex itself which is a monoclonal antibody or is residual
myeloma if there’s any question a blood sample can be sensed by the doctor to
Janssen the maker of Darzalex for further testing immunofixation
electrophoresis of blood or urine is the counterpart to SPEP and UPEP IFE
tells us that type of monoclonal protein in the blood and/or urine but not the
amount well SPEP and UPEP tell us the amount but not the type the result of
the IFE is that a certain type of monoclonal protein is either there or
not there like UPEP and SPEP IFE also separates proteins by electrical charge
at this time only the monoclonal abnormal antibody proteins are separated
out not the normal ones as with SPEP Darzalex can influence the results of
IFE if a patient has IgG Kappa myeloma and is being evaluated for complete
response the patient may be in a very deep complete response but a tiny band
of IgG Kappa will show up on the test read out if the pathologist is unable to
make a determination whether the band is from IgG Kappa myeloma or from Darzalex
Janssen will do so quantitative immunoglobulin testing or QIg is done
to see if any of the five immunoglobulins are abnormally high or
low in myeloma one type may be high while the others are low because
remember your your immune response is suppressed so your normal
immunoglobulins are usually a bit lower if your myeloma is active and you’re
secreting a certain type of monoclonal protein QIg measures the
total of each heavy chain antibiotic type in the blood
IgG immunoglobulin G IgA IgM IgD and IgE most myeloma patients have either IgG or
IgA myeloma quantitative immunoglobulins measures both normal immunoglobulin and
abnormal immunoglobulin coat proteins and one lump sum if an increase in an
immunoglobulin is found further testing with IFE is required to see if it is
myeloma related QIg is often done as part of early screening for myeloma if
the total protein test from your metabolic panel result is high QIg
determines if the elevated protein is actually globulin not albumin and will
indicate which globulin level is elevated some doctors also use QIg to
follow patients with IgA myeloma since as I mentioned it’s difficult to assess
IgA myeloma with SPEP okay here’s here’s a difficult test Freelite testing is
used throughout the myeloma disease course for patients whose myeloma cells
secrete free light chain proteins most patients myeloma cells secrete both
heavy and light chains the light chains are named either Kappa or lambda after
the two doctors who discovered them whose names were Korngold’s Kappa and
Lipari Lambda which is L in Greek testing for
free light chains in the blood before they are filtered out through the
kidneys into the urine is a highly accurate and sensitive test on the slide you
see the blue and pink Y shaped structure of the intact immunoglobulin protein
blue heavy chains with pink white chains bound to them much of the time in
healthy individuals and in myeloma patients there are extra light chains
that are not attached to heavy chains they are
called free light chains and I have no idea why we make them some patients
myeloma cells only secrete light chain protein and no heavy chains and some
myeloma patient cells secrete so little monoclonal protein at all that only the
very sensitive Freelite test can be used to measure it so Freelite is an
especially useful test it is useful for almost all myeloma patients for
diagnosis prognosis and monitoring response to therapy it’s used to monitor
early relapse during remission periods as well this is an inexpensive and widely
available test not to be confused by your doctor with an older test called
kappa/lambda light chain comma total comma serum that test has a different
code than the Freelite test it measures both bound and unbound light
chains while the Freelite test measures only the unbound or free light
chain sometimes a doctor will inadvertently check off the wrong test
on the lab request form and your results will cause you with concern and you will
call the info line make sure you’re getting the free light chain assay or
Freelite test if that’s the brand-name free light testing measures the involved
free light chains that are made by your myeloma cells as well as the uninvolved
free light chains that are made by normal plasma cells that we all have we
all have some freely circulating normal light chain antibodies in our blood at
any given time, the ratio of capital lambda helps determine if there are too
many light chains of one kind or another indicating myeloma if the number of
Kappa and lambda light chains are both high but the ratio between them is
within the normal range it indicates a kidney problem not myeloma the ratio
as you can see is calculated by doing a division problem you divide the number
of Kappa by the number of lambda chains the
heavy-light assay is a blood test that measures the intact immunoglobulins like
you those you saw in the picture with the blue and the pink with light chains
bound to heavy chains not only does it measure the intact heavy and light chain
protein made by the myeloma cells it also measures the heavy and light chain
bound immunoglobulin protein made by normal plasma cells if your myeloma
protein is for example IgA Kappa the heavy plus light chain intact
immunoglobulins that is its normal counterpart will be IgA lambda IgA IgA
lambda chains are going to be your normal healthy ones and the iga Kappa
ones are your myeloma chains immunoglobulins IgA Kappa is best
paired with IgA lambda if the intact immunoglobulin involved in your myeloma
is high the Hevylite test will show that the Hevylite test will also show
that that uninvolved intact immunoglobulin paired with your myeloma
and made by normal plasma cells is low because when you have active myeloma
your ability to make normal antibodies is decreased the test is often used to
measure IgA heavy chain protein because IgA I will repeat is sometimes
difficult or if just by no difficult to assess with SPEP our next tests are
studies that are done on bone marrow samples remember that myeloma usually
grows inside the bone marrow bone marrow aspiration is done with a syringe which
draws out the liquid part of the marrow a core biopsy is done with a special
hollow needle and it captures a sample of the spongy bone in the marrow along
with its contents this is an uncomfortable and painful study I don’t
have to remind you of that so there are no strict rules for
often it must be performed it’s the only eyes on study of the myeloma cells under
a microscope all other tests rely on indirect markers of what myeloma cells
are doing the pathologist who looks at your myeloma cells under the microscope
writes a report detailing how many of the cells in the sample or abnormal
plasma cells and what they look like words like mature immature and atypical
may appear in your report immuno phenotype is done by flow cytometry it
identifies protein markers on the surface of myeloma cells it is used to
determine both stringent complete response and minimal residual disease
known as MRD which is even less myeloma than stringent complete response the IMF’s
Black Swan Research Initiative funded Next Generation Flow test was developed
especially to detect minimal residual disease and is sensitive enough to
detect one myeloma cell among every one million plasma cells sampled from the
bone marrow the next two slides cover bone marrow tests of chromosomes and the
genes on them standard cytogenetics is an old test it is used to observe
what happens to the chromosome in a cell’s nucleus during cell division it’s
also called karyotyping because a karyotype is the number and appearance
of chromosomes in a cell’s nucleus loss of chromosome 13 during cell division
can be detected better with cytogenetics than with the next test I’ll discuss
called FISH loss of chromosome 13 is usually an indication that other genetic
abnormalities are present in the myeloma cells fluorescence in-situ hybridisation is
FISH neither cytogenetics nor FISH gives us
complete information by itself so they are often both done
in FISH testing each chromosome is identified by different color if we see
a small section of one color within a chromosome of another color we know that
a segment of genes from one chromosome got mixed in with another chromosome
during cell division if part of a chromosome is missing that’s visible too
the pathologist can identify those translocations the movement of little
pieces of one chromosome to another or deletions of genetic material from the
chromosomes that are known to be high-risk in myeloma such as
translocation 414 which means pieces of chromosome 4 and chromosome 14 or
deletion 17p deletion 17p is the loss of the short top part of chromosome 17
where a major tumor suppressor gene called p53 is located you don’t want to
lose a tumor suppressor gene most myelomas are it’s not something you have
control over of course but that is a high risk mutation the final pieces of
our puzzle are imaging studies among other things imaging studies are used to
assess bones the “B” in the CRAB diagnostic criteria bone disease in
myeloma is always related to bone loss our first and oldest imaging study is
the x-ray or skeletal survey x-rays are simple and inexpensive studies in
addition to exposing patients to radiation they’re not particularly
sensitive and are not useful for diagnosing early disease you have to
have lost 30% of the hard outer part of the bone before an x-ray will show bone
damage x-rays do not show early abnormal areas in the bone
are called focal lesions in the graphic on this slide
you can see the loss of the hard outer bone that we call a lytic lesion as well
as the massing of myeloma cells within the bone marrow that does not appear on
an x-ray x-rays also do not show bone healing in places where there is no
longer active myeloma so x-rays are not useful for monitoring
response to treatment MRI magnetic resonance imaging uses magnetic energy
not radiation and that’s a good thing for patients it is highly sensitive for
the detection of early bone marrow involvement both focal lesions you saw
on the picture before bone destruction actually occurs MRI can distinguish
between benign and malignant vertebral fractures a benign vertebral fracture is
one caused by osteoporosis which is common in older women for example MRI
can detect spinal cord compression and soft tissue masses those which are
usually called in myeloma plasmacytoma their masses of
cancerous plasma cells MRI is not good for monitoring because it takes up to
nine months for healing on it to show up on an MRI so if you’re comparing a new
MRI to an old one within those nine months you may not see any sign that
there’s no myeloma there anymore even though there really isn’t MRI may
require the contrast agent gadolinium gadolinium and that can be a problem
gadolinium contrast can we’ve always known might be harmful to myeloma
patients with kidney damage but on Friday of last week a committee set up
by the Food and Drug Administration voted to recommend a new warning for
gadolinium-based contrast agents used in MRI for everybody
the FDA asked the common become for advice on how to weigh recent
findings of gadolinium retention in the brain and other organs and how to
minimize potential risks moving forward please discuss the use of gadolinium
contrast with your oncologist before she or he sends you for an MRI with contrast
particularly if you already have kidney issues request that the study be done
without contrast computerized axial tomography or CT which used to be known
as a cat scan when I was young is a cross-sectional three-dimensional x-ray
it’s more sensitive than x-ray for small lesions and for those soft tissue masses
it does expose patients to radiation although there’s a technique called low
dose CT that obviously exposes patients to less radiation it is not good for
monitoring because the appearance of lytic lesions those the loss of that
hard part of the bone may not change even if there is no longer active
myeloma and again although it’s not with gadolinium CT may require contrast
agents that pose problems for those patients with kidney damage patch or
positron emission tomography is a whole-body real-time study it means that
the radiologist can see where the myeloma is actively
growing in the body at the moment the test is being done because those areas
where there are active myeloma cells light up it’s very useful when a patient
has non secreting myeloma cells that make no monoclonal protein because if
the myeloma cells don’t secrete monoclonal protein you need something
other than bone marrow biopsy to help monitor the disease a PET CT is a PET
with CT only of those areas that light up on PET
some doctors are now using PET MRI instead of PET CT for patients who
require more frequent monitoring with PET in order to avoid the radiation from
the CT of course pet is expensive even more so when CT or MRI is added so all
of this requires insurance approval PET is used in diagnosis therapy its
assessment and prognosis it shows if there is extramedullary disease which is
myeloma that grows outside the bone marrow the need for PET scanning is
included in the IMWG’s consensus statement on how to assess response to
treatment pet is considered a requirement along with either
Next Generation Flow or next generation DNA sequencing in order to assess
minimal residual disease because both of those studies are based on bone marrow
samples sometimes myeloma is extramedullary meaning that it grows
outside the bone marrow PET imaging will pick up areas where myeloma is growing
both inside and outside the bone marrow so here’s our complete puzzle you’ll
notice that the edges of the puzzle are not complete but are open to still other
pieces first and foremost there is no lab cast biopsy or imaging study that
will negate the importance of a physical exam and the observations of your
treating doctor no amount of testing will ever tell the whole story there are
so many other factors influencing the behavior and outcome of your myeloma all
the other things besides from a alone myeloma that may be going on with your
body and your health will influence your myeloma disease course including other
illnesses you may have your level of pain your emotional state your stress
level your support system and whether or not you are well covered by insurance here are some resources for more
information that you can the two booklets we do have in the Understanding
series on testing our Understanding Your Test Results which is kind of a more
detailed version of what I just spoke about and Understanding Freelite and
Hevylite tests because those two tests require a booklet of their own and
it is currently being rewritten by our friend at the Binding Site which makes
those tests an IMF video on EMR or Electronic Medical Records is available
on YouTube we also have a tip card covering the important features of that
video and then we have a page on our website with information about that
Next Generation Flow test for MRD testing and other projects of the
Black Swan Research Initiative and now I will turn it over to Robin and Dr. Abonour okay thank you so much for the useful
explanation of current tests and results in myeloma Debbie I’m sure that patients
and caregivers will be able to have better conversations based on
misinformation question and answered part of our half an hour so if you have
not already done so please remember to take you into the control panel box
under questions and as a reminder we ask that questions be general in nature and
specific to myeloma to benefit all the listeners on this webinar and I also see
that we have a view myeloma support groups that are participating on this
live webinar so a big shout out to West Bend Wisconsin and a few the other
groups out there that are gathering tonight what a fantastic way to learn so
I think we’ll move on to our questions now Dr. Abonour the first one
comes from Jack and he asks would Darzalex also affect MRD minimal residual disease results like it does IFE and SPEP. Well so
let’s just say that Darzalex or daratumumab is a monoclonal
antibody so it’s like the myeloma protein is unique and the subtype of
that is an IgG Kappa now when people look for minimal residual disease they
try to find so a specific marker for the myeloma which is not really sort of
present in the monoclonal antibody daratumumab or Darzalex so if you find in
the serum protein electrophoresis in the blood this monoclonal protein IgG Kappa
but you do have a specific marker or you’re doing the flow cytometry you may
not you know you you will get overcome this confusion that having this
monoclonal antibody in the blood from the infusion so I think if you are
looking for MRD minimal residual disease by flow cytometry or by what we call
sequencing of the DNA you will be able to detect the presence or the absence of
residual disease because you’re not using the same thing as we use in serum
protein electrophoresis and immuno fixation looking for the type of the
immunoglobulin now we’re looking more either what’s on the surface of the
myeloma cells that make them unique or what’s inside the myeloma cells which
making you unique the genetic makeup so actually the MRD is a good way testing
to you know sort of get rid of this confusion about this minimal small
monoclonal protein you see was the infusion of Darzalex. Okay yes that’s
excellent our next question is from Scott and Scott asks
what tests and trials are there for aggressive smoldering myeloma? Well I
mean I say yeah that’s there are a lot of internal testing for smoldering
myeloma there are in unique testing that we are using other than looking at the
amount of monoclonal protein the certain cytogenetic and then come up with a high
risk profile I think a lot of people are sequencing smoldering myeloma to try to
come up with a special profile for high-risk smoldering myeloma there in
terms of trials there are tons of trials you know that will be available with
really the the goal is to see if we can get more patient into minimal residual
disease negative state in the smoldering high-risk myeloma in order
to cure myeloma and so if we succeed in the high-risk smoldering myeloma and we
can actually get patient into MRD negative
minimal residual disease negative state for more than a year we maybe start
talking about curing myeloma. Okay the next question is from Chris and the
question is are those with non-secretory myeloma only of the light chain disease
type? Can you repeat the questions again sure are those with non-secretory
myeloma only of the light chain disease type? No, by definition I mean when you
measure either this in serum a monoclonal protein in the urine a
monoclonal protein or you have an elevated light chain by the free light
chain assay then this is the secretory myeloma when you cannot measure anything
that will be non-secretory myeloma and when we use the serum protein
electrophoresis the urine protein electrophoresis
and the free light chain assay 99% of the patients will have something
measurable unfortunately the 1% or less who don’t have anything that to measure
to follow the disease we have to depend on either a PET scan or the bone marrow
biopsy. Okay the next question is can you comment on the recent FDA
closing or halting of myeloma immune therapy trials? Obviously that’s not the
subject of the discussion tonight but I think what happened is that the FDA
noticed that there wasn’t a huge difference in terms of the outcome there
weren’t you know large number of patients who received immune checkpoint inhibitor did well compared to the
people who didn’t receive checkpoint inhibitor what they notice also is that
there were more death on when the patient gets checkpoint inhibitor PD-1/PD-L1 inhibitor with the immunomodulatory drugs so I think that the FDA was
obviously correctly scared to see ok what’s going on here here why are we
seeing more death is there more autoimmune disorder are we making the
myeloma more aggressive so I think we going back to the drawing board to see
what are these deaths what are these toxicity can we use these
you know checkpoint inhibitor which is really I think fascinating I mean they
work well in lung cancer they work well in melanoma and renal cell cancer and if
we can get them to work well in myeloma without causing you know side effects I
think that could be amazing because awakening the immune system to make it
recognize myeloma and kill myeloma is an advantage but I think you know at this
point two trials showed increase mortality death when people get those
combination of iMids like pomalidomide/Pomalyst or
Revlimid with these checkpoint inhibitor so the FDA for the clinical hold on
these trials and similar trial until we figure out what’s wrong okay. Okay the
next question is from Alexa what is the standard range to SPEP and UPEP? Standard range is not to have a monoclonal protein in the urine or the
serum so it should be zero so when you detect the monoclonal protein that’s
abnormal and if you detect monocle protein in the urine the serum
basically you have disease when it’s gone the disease in remission so there’s
no standard range. Okay next question is from Ed how often should a patient have a
PET-CT testing and also taking into consideration the amount of radiation
exposure over time? Yeah that’s a very very good questions and I think we’re
still trying to figure out how to do it so I think in the newly diagnosed
patients you know when we are getting away with this simple x-rays we call
them the skeletal survey and some people are using either a whole body CT scan
whole body MRI or a PET scan and a PET scan as you heard from Debbie is a
really good test when you have disease outside the bone marrow so if you have
somebody present with what we call them this tumor the plasmacytoma
and you know that they exist in certain way and you want to follow up on their
patients a PET scan can be useful so I think at diagnosis they may be useful as
a follow-up if you find something that you need to see if they responding or
not or when the disease relapse and you don’t know the extent of the relapse you
can do a PET scan so I think a diagnosis at relapse and if there is something
you cannot follow up with any other imaging then you
do the PET scan for follow-up okay. Okay this question kind of tails on to what
you just answered Kevin would like to know when you’re
relapsing how do you measure the myeloma what tests should you be redoing to
determine restarting your treatment? So the test we do for relapse so obviously
you are following the monoclonal protein in the serum or they are in all the time
so if it was zero and now it’s one gram then that’s a relapse if the free light
chain was normal ratio was normal and now the free light chain is elevated and
the ratio is abnormal then this is a relapse and so you can do and say this
patient has a chemical relapse but you also have to see if the patient has what
we call symptomatic relapse are they having any of the CRAB criteria
high calcium, kidney dysfunction, anemia or bone destruction so based on the
symptoms if the patient has a new back pain you do an MRI if the patient has
you know not feeling well you obviously need to do chemistry to check the
calcium and the creatinine so it depends on the clinical conditions and and
what’s happening with the serum test mm-hmm. Okay we have a question from
Chris who is asking for you to please comment on the new test known as the
total body MRI or DWI-MRI versus PET scan? I think these tests are going to so
first of all I mean that the MRI is much more sensitive I said than the skeletal
survey so what you’re going to see on an MRI you’re going to see the bone
structure you’re going to see if there’s a lesion inside the bone or outside the
bone sometimes you know you can see by MRI if there’s an active you know sort
of lesion but it’s not very sensitive like the PET scan
let’s can you use a sugar that is radioactive and it’s picked up by you
know cells that multiply fast so if you have rapidly growing myeloma very
aggressive myeloma and the sugar is picked up by the myeloma myself then it
will light up and then you can see it so it’s a little better but the whole body
MRI is becoming a replacement to the skeletal survey to be able to see the
lesion that you cannot see on a simple x-ray. Can I add one thing here only
Chris and I happen to be at a group subgroup meeting at the IMWG summit
on imaging and their planning they have proposed and are planning a big clinical
trial to compare diffusion-weighted imaging MRI or DWI-MRI versus PET scan
and it’s going to be at centers all over the place
they were our investigators there who are interested at all over the globe
so that will be conducted in the coming years oh so we don’t have an answer on
what’s the best test if this is going to be done for patients who have had a stem
cell transplant to monitor them before and after transplants. Okay people have
enough time to take maybe one more question and then we’ll do a little
wrap-up so the last question is going to come from LaDuke and the question is how
often should an asymptomatic high-risk smoldering multiple myeloma patient
otherwise healthy how often should testing be done like bone marrow
biopsies, MRIs, 24-hour urine? So I think the high-risk smoldering myeloma
I will follow them with blood tests or urine test I will not repeat the bone
marrow until I see a reason for it like for example they becoming too anemic or
the counts are abnormal I would not do a routine PET scan or MRI unless there is
symptoms or significant rise the monoclonal protein so I think just
following the patient by good history good physical exam and the blood test is
adequate. Okay so thank you Debbie and Dr. Abonour are for taking the time
tis evening to help us make more sense of all these extensive and new myeloma tests
and results a few reminders for everyone tonight
the IMF website is a wealth of information so I hope you’re accessing
it daily or weekly as you have time and that’s myeloma.org the replay of this
webinar will be available early next week and you can access this as well as
all previous IMF webinars at myeloma.org and simply click on IMF TV. A few
important reminders are the last IMF patient family seminar of 2017 is in
Dallas, Texas on October 6th and 7th it’s a two-day program and there are three
IMF regional community workshops left this year happening in the fall one in
Charlotte, North Carolina on September 23rd another in Fort Wayne, Indiana on
September 30th and the last one is in Duke,North Carolina on November 11th so
don’t forget if you have questions the IMF Infoline has answers and that’s 1-800-452-CURE which is 2873 Missy, Judy and Paul are always
happy to take your calls our thanks to each of you for participating on this
webinar tonight and we hope you found it helpful and once again to Debbie Birns
and Dr. Abonour our your experience and expertise is always so much appreciated
and we thank our sponsors again Celgene, Janssen Pharmaceuticals and
Takeda Tncology and most importantly thanks to each one of you on this call
tonight we wish you well have a wonderful evening
that concludes tonight’s call