Multiple Myeloma: Treatment Advances and Clinical Trials

Transcript

• 00:00Joining us today to talk a little
• 00:03bit about multiple myeloma.
• 00:04I am new for Barnwell,
• 00:06the myeloma doctors here at Yale and we will
• 00:09be talking about three different topics,
• 00:12each about 15 minutes long and then
• 00:15will have 15 minutes of discussion Q&A.
• 00:18So I will be talking about understanding
• 00:21myeloma come my colleague, Doctor
• 00:23Sabrina Browning will be talking about.
• 00:27More specific.
• 00:28About the new treatments out there
• 00:32for multiple myeloma and or.
• 00:35Really excellent physician assistant
• 00:37Tara Anderson will be talking about
• 00:40Texas cities of certain drugs and
• 00:42then we'll have our the rest of
• 00:44our team join us for the question
• 00:46and answer and doctor Terry Parker
• 00:49and Doctor Natalia will parts so.
• 00:52With that we will start our.
• 00:55Session.
• 00:572nd.
• 01:07Alright. So my goal for the next
• 01:1115 minutes is to give you some
• 01:14insights into understanding what is
• 01:16multiple myeloma and some general
• 01:18principles of how we think about
• 01:21treatment for multiple myeloma.
• 01:26I have no disclosures.
• 01:29I'd like to start by talking
• 01:31about the bone marrow,
• 01:33which is where my llama lips,
• 01:34now the bone marrow,
• 01:36is a spongy part of the bone,
• 01:38and it's in charge of making some
• 01:40important cells in our body.
• 01:42It makes red blood cells,
• 01:43which carry oxygen and give us energy.
• 01:46It makes platelets which prevent
• 01:48bleeding and it makes white blood
• 01:51cells which help fight infections.
• 01:53Now, one of the white blood
• 01:55cells is called plasma cells,
• 01:57and these plasma cells help our
• 01:59bodies fight infection by making
• 02:01antibodies and antibodies are proteins
• 02:03that bind to foreign substances,
• 02:06for example, like a bacterial infection,
• 02:08and it helps kill it and
• 02:10clear it from the body.
• 02:12Now, under normal circumstances
• 02:14we have a small amount of these
• 02:17plasma cells in the bone marrow,
• 02:19roughly 5% or so,
• 02:21and they make a variety of antibodies.
• 02:24So uhm, no antibody is like the other.
• 02:28Now, if one of these plasma
• 02:30cells is now becoming cancerous,
• 02:32it's abnormal normal.
• 02:33It's able to replicate itself
• 02:35and make a clone out of itself,
• 02:37and in doing that it over crowds the
• 02:40bone marrow with too many of these
• 02:42abnormal plasma cells and they no
• 02:45longer make variety of antibodies,
• 02:47but rather they make a lot
• 02:49of 1 type of antibody.
• 02:52And this is what we called the
• 02:54monoclonal protein M spike and protein,
• 02:57all different names for the same thing.
• 03:00And this antibody can be one of the common
• 03:03antibodies that are found in our bodies,
• 03:06most commonly,
• 03:07IgG IGA is often also seen and more
• 03:10rarely IG M and IG D Now a part of
• 03:13that protein is called the light chain,
• 03:17and it's either Kappa or Lambda.
• 03:20So a monoclonal protein can be identified,
• 03:23for example,
• 03:24is an IgG Lambda and IGA Kappa,
• 03:26and that is that that
• 03:29clone for that individual.
• 03:32So how does multiple myeloma affect the body?
• 03:34How does it make someone feel?
• 03:37I'm gonna talk about some of the common
• 03:40manifestations of multiple myeloma,
• 03:42but I want you to remember that
• 03:44not all of these are found in every person.
• 03:47OK,
• 03:48so the first thing is high calcium level OK,
• 03:51and I and I put this.
• 03:53See for that here and
• 03:55sometimes high calcium levels.
• 03:56It's not that bad.
• 03:57It's not going to make anyone
• 03:59feel anything differently,
• 04:01but if it's very high it can make
• 04:03someone feel unwelcome cause confusion.
• 04:05You can cause some Constipation
• 04:07or abdominal discomfort.
• 04:08So I put the picture there to
• 04:11just to signify that the next
• 04:13is represented by the letter R.
• 04:15So are standing for renal,
• 04:17another word for renal is kidney,
• 04:20so my Loma cells and the proteins that
• 04:23they produce can cause damage to the kidneys.
• 04:26Next,
• 04:26a four anemia,
• 04:27so that's low red blood cell count and
• 04:30therefore you have less oxygen going around.
• 04:332/2 essential organs.
• 04:34People feel tired in this situation.
• 04:36They're not able to do.
• 04:38Their daily activities.
• 04:41And lastly,
• 04:42be standing for bone pain or bone lesions,
• 04:45and a lesion is any kind of
• 04:47abnormality seen in the bones.
• 04:49And so in myeloma you can have either
• 04:52holes in the bones and this can make
• 04:54the bones weaker and you can have
• 04:57fractures which can cause pain,
• 04:59but sometimes more rarely we see
• 05:01actually accumulation of these
• 05:03abnormal plasma cells forming a ball
• 05:05or a mass and this can be within
• 05:07the bone or outside of the bone
• 05:10and we call these plasmacytomas.
• 05:12So you can see the CRA beat spells crab
• 05:15and this is the famous crab criteria or
• 05:18crab symptoms that we often talk about.
• 05:21Or you might have read.
• 05:24Now the definition of myeloma has
• 05:27changed over time for many many years.
• 05:30Basically, yes,
• 05:31you had to have these abnormal plasma cells,
• 05:34but you had to have met one at
• 05:37least one of the crab criteria
• 05:39that we just talked about.
• 05:42Things changed in 2014.
• 05:43The criteria changed and now we
• 05:46have slim crepe.
• 05:47How did we get slim?
• 05:49So to really understand why
• 05:51and how Slim came about,
• 05:53we have to go back and
• 05:55understand the precursor,
• 05:56the condition that comes before
• 05:58multiple myeloma called this
• 05:59the precursor states myeloma.
• 06:00We know that all patients who have
• 06:03myeloma before they developed
• 06:04in myeloma had these abnormal
• 06:06plasma cells exist within a small
• 06:08quantity small quantity and it
• 06:10didn't cause any trouble so you
• 06:12wouldn't know you had them unless
• 06:15you actually go and look for them.
• 06:18The majority of patients with M Gus
• 06:21actually don't progress to myeloma,
• 06:24but some.
• 06:27Do you move on to the next
• 06:28step and the next step is what
• 06:31we called smoldering myeloma.
• 06:32Now smoldering my luma and us both
• 06:34don't have any crab criteria.
• 06:35What we called the precursor states,
• 06:37but the difference between them
• 06:39is smoldering element has more
• 06:40plasma cells as you can see here.
• 06:42If you go by the correct by,
• 06:44the technical definition should
• 06:45have more than 10% plasma cells
• 06:47in the bone marrow.
• 06:49But what does this mean to the person right?
• 06:52How does that affect you?
• 06:53Uhm, well,
• 06:54the risk of progression to myeloma is
• 06:56slightly higher in the smoldering group,
• 06:58where we have a 10% an average
• 07:00risk of progression to myeloma.
• 07:02Compared to 1% in the US population.
• 07:07Now looking at the Group of smolder
• 07:09malama little bit more closely,
• 07:10yes, we have a very well.
• 07:13Defined, you know, definition for this,
• 07:15but the folks in this group are quite
• 07:18diverse and not everyone is the same,
• 07:20so we have.
• 07:23Patients here that actually behave
• 07:25their disease behaves more like M Gus,
• 07:27and they never progress to multiple myeloma.
• 07:30On the other hand,
• 07:31we have patients who behave
• 07:33more like myeloma,
• 07:35and they actually progressed to
• 07:36those crab symptoms fairly soon
• 07:39after the diagnosis of small drink.
• 07:41So many researchers in the community
• 07:43of myeloma have focused their
• 07:45attention to this group of patients
• 07:47trying to figure out who really
• 07:50should be in the myeloma group.
• 07:52And that's where this slim criteria.
• 07:54That's why they identified
• 07:57three important qualities.
• 07:59Come in, that's. Here so S stands.
• 08:04But sorry, three important qualities
• 08:06that that predicts the rapid
• 08:09progression to multiple myeloma.
• 08:121S stands for 60% or more plasma
• 08:14cells within the bone marrow.
• 08:16Li stands for a light chain ratio
• 08:18over 100 and M stands for MRI,
• 08:21showing more than one lesion,
• 08:22and this is important 'cause we used to
• 08:25just use X rays to look for these lesions.
• 08:28These holes in the bones.
• 08:30Now we know this is not enough and we
• 08:33need to use more advanced imaging for
• 08:36these particular patients to identify.
• 08:38No lesions that would move
• 08:41you into the myeloma category.
• 08:44So now that we have no diagnosis of myeloma,
• 08:47what do we do?
• 08:48When is our goal for treatment
• 08:50for this disease?
• 08:51So anyone that has myeloma has a
• 08:53certain amount of disease at diagnosis.
• 08:55What we called the disease burden,
• 08:57and we measured this through
• 08:59one of the blood.
• 09:00So we look for that M protein.
• 09:02The bone marrow looked the amount
• 09:04of plasma cells in the bone marrow,
• 09:07and thirdly imaging, right?
• 09:08So we look at the amount of bone disease,
• 09:11but we also look for these.
• 09:13The solid form of myeloma.
• 09:14The PLASMACYTOMAS,
• 09:15which is important to know.
• 09:17And.
• 09:18Yeah,
• 09:18my goal is to kill as many plasma
• 09:21cells as we can to get these deep
• 09:24responses and to keep people in
• 09:27response for as long as possible.
• 09:30Unfortunately, this you know some point.
• 09:32The disease does come back.
• 09:34We do not think myeloma is a
• 09:36curable disease at this time.
• 09:38So when the disease comes back,
• 09:40we do have other treatments and
• 09:42we bring the disease back down
• 09:45and this pattern goes on and on.
• 09:50I want to take just a few minutes to talk
• 09:53about response assessment for myeloma.
• 09:55How we assess the response?
• 09:56So as I mentioned, we look at the blood.
• 09:59We look at this protein.
• 10:00We also look at the bone marrow to look
• 10:02at how many plasma cells are there.
• 10:04So once we start treatment we measure the
• 10:06lab 'cause it's very easy to look at blood
• 10:09work and we see how the protein falls.
• 10:11If you've had a 50% reduction,
• 10:12we call this a partial response.
• 10:15Uhm, if you've had disappearance
• 10:16of this protein and then when
• 10:18you look at the bone marrow,
• 10:19you don't find any of these abnormal
• 10:21plasma cells when you look with your eyes.
• 10:24It's then we call this a complete response,
• 10:27which is great.
• 10:28Nowadays we actually have even more
• 10:31sophisticated tests tests that look
• 10:33at really microscopic level of disease
• 10:35looking at the DNA of the plasma cells,
• 10:38and if we don't find this DNA
• 10:40in the bone marrow's.
• 10:43We call this the deepest response.
• 10:46Call it minimal residual disease,
• 10:48negativity murdy negative negativity
• 10:51and you might have heard about this.
• 10:55This measurement and I just wanted
• 10:57to bring it up here so people
• 10:59understand what this really is
• 11:00and what are we looking at.
• 11:02And we do this in clinic and it's also
• 11:04been investigating clinical trials
• 11:05and this is a very important point.
• 11:11So how do we get these deep responses?
• 11:14How do we choose initial therapy initial
• 11:16therapy in my limits called induction.
• 11:18OK, so we're lucky we have a lot of
• 11:21different drugs and they're very
• 11:23effective at killing plasma cells,
• 11:25and they've been used in induction.
• 11:27I categorized them here under different
• 11:29colors and shapes to signify that each
• 11:32group represents a drug that acts a little
• 11:34bit different in how it kills my llama,
• 11:37and we like to combine the drugs
• 11:39in these different groups.
• 11:41To get the best responses as we can.
• 11:44And I'd say for the most part,
• 11:47we really and think that
• 11:50combining proteasome inhibitors.
• 11:51Juicy down here,
• 11:53along with Imids,
• 11:54a module to her drugs and steroids
• 11:56as being very effective and one of
• 11:59the most commonly used treatments has
• 12:01been Velcade REVLIMID index method zone.
• 12:04I think one of the more recent
• 12:06advances is adding daratumumab,
• 12:08the monoclonal antibody to this regiment,
• 12:10and this is also been shown to have
• 12:13very very great responses,
• 12:15and so you know on one hand the coin one
• 12:19side of the coin I'm telling you about.
• 12:22Obviously want very effective treatment,
• 12:24but we also want to look at the
• 12:26other side and how this dream is
• 12:29affecting the individual right.
• 12:30So these drugs have toxicities have
• 12:32side effects we want to make sure that
• 12:35the patient the individual can tolerate it.
• 12:37So just to give you an example
• 12:39from someone with kidney disease
• 12:41which you can have with my Loma
• 12:43doesn't tolerate limit very well.
• 12:45So in this case we might use cytoxan instead.
• 12:48You know some folks you know four
• 12:50or even three drug books might be.
• 12:52Too difficult,
• 12:53and in that situation we use two drugs,
• 12:56so the bottom line is we want a
• 12:59very effective treatment that will
• 13:00be well tolerated,
• 13:01and that's how we choose
• 13:03our induction treatment.
• 13:06Initial therapy doesn't stop with induction,
• 13:08as many of you know,
• 13:10we have several cycles of induction,
• 13:12but then we move on to different treatments.
• 13:14So for some folks we do recommend high doses
• 13:16of chemotherapy and stem cell transplant,
• 13:18and that's again to deepen the responses
• 13:21and prolong the time you stay in response.
• 13:23But this is.
• 13:26Cancer treatment with significant
• 13:27side effects and that recovery time
• 13:30so it's not meant for everyone.
• 13:32It is something to decide
• 13:34on individual basis.
• 13:36Regardless, if you get a transplant or not,
• 13:38after induction you move onto to
• 13:41maintenance and maintenance is
• 13:42really you know what it stands for.
• 13:44It's meant to maintain the the disease and
• 13:47are good levels so it doesn't come up,
• 13:50but meant to be well tolerated so
• 13:52you can continue this for years.
• 13:54So often we use one drug or maybe
• 13:572 for some situations,
• 13:58or the disease might behave a little
• 14:02bit more aggressively and we continue
• 14:04this for as long as as we can.
• 14:07As I mentioned,
• 14:08at some point the disease does
• 14:10come back and we do need to think
• 14:13about different treatments.
• 14:14So how do we decide treatment at relapse?
• 14:17Well, we choose a different combination.
• 14:19Again,
• 14:19we'd like to choose combinations
• 14:21from different classes of drugs here,
• 14:23so I added a few to my list to
• 14:26my treatment menu.
• 14:27Here we have palm list,
• 14:29which is the 2nd generation of the relevant.
• 14:32That meant we also have other other
• 14:34monoclonal antibodies, like below,
• 14:36and we basically choose something
• 14:38you have not had before.
• 14:39Often we use pomalidomide as the
• 14:41second it you include pummel,
• 14:43admired in the combination.
• 14:45Second treatment, and then if you
• 14:47need a third or fourth treatment,
• 14:49we're very lucky that our treatment
• 14:51menu is growing and is continuing to grow.
• 14:54So we have selling X or we have a blunt wrap.
• 14:58We have now male flap.
• 15:01And most recently, the cartee avec ma.
• 15:04And least, but not.
• 15:06Sorry,
• 15:07last but not least clinical trials,
• 15:09so we have an assortment of clinical
• 15:12trials where it gives opportunity to try new,
• 15:15very possibly very effective
• 15:17treatment for myeloma.
• 15:18So with that I'd like to conclude
• 15:20my section of the talk and move
• 15:23on to doctor Sabrina Browning.
• 15:25He will talk about the details
• 15:28of these newer agents that we
• 15:30have for to treat myeloma.
• 15:47Great, OK, so good evening everyone
• 15:49and thank you again for joining us.
• 15:52Come again. My name is Sabrina
• 15:54Browning as Doctor Barr stated.
• 15:56I am one of the doctors in our multiple
• 15:59myeloma gammopathy program here at Yale.
• 16:01So in this next part of our discussion
• 16:04I will review recent advances in the
• 16:06treatment of multiple myeloma and
• 16:08specifically will focus on the newly
• 16:11approved medications for patients.
• 16:12Either that have relapsed so with
• 16:15recurrence of their disease or refractory.
• 16:17They're not responding to
• 16:18their current treatment.
• 16:24And I have no disclosures to report.
• 16:28So fortunately, as a result of the
• 16:31introduction of new medications and
• 16:33combinations of my Loma agents,
• 16:35as stated by Doctor Bar
• 16:36over the last few decades,
• 16:38there has been significant improvement
• 16:40both in prognosis and quality of life.
• 16:43For those letter living with
• 16:44multiple myeloma, the major classes
• 16:46of medications used in myeloma,
• 16:48as touched upon by Doctor Bar,
• 16:50which may be familiar to you or listed here,
• 16:53and they include the immunomodulatory
• 16:55agents or imids proteasome inhibitors,
• 16:57or Pi monoclonal antibodies.
• 16:58Alkylating agents and the histone
• 17:00DSS release inhibitor referred
• 17:02to as put in a panobinostat.
• 17:04These medications have been or are
• 17:07currently being studied as a part of.
• 17:10Combination regimens and many
• 17:11are targeting earlier in disease
• 17:13course as Doctor Barr mentioned,
• 17:15our treatment going myeloma is really
• 17:17to achieve what we refer to as deep or
• 17:19maximum responses to therapy that are
• 17:22prolonged without disease progression.
• 17:24And while we won't review this
• 17:26agent in detail today,
• 17:27I've signaled Isatuximab in the chart
• 17:29here as a more recently approved
• 17:31antibody that targets a protein known
• 17:33as CD 38 found on immune cells and
• 17:36myeloma cells and isatuximab is now
• 17:39approved for use in combination with.
• 17:41Both pomalidomide and dexamethasone,
• 17:42as well as with carfilzomib
• 17:44and dexamethasone,
• 17:45and is being studied further
• 17:47in additional clinical trials.
• 17:50So what has remained a challenge
• 17:52and an area where improvements
• 17:54are essential is the treatment of
• 17:56individuals with myeloma who have
• 17:58received multiple lines of therapy,
• 18:00particularly those who are no
• 18:01longer showing response to the
• 18:03P eyes or proteasome inhibitors.
• 18:05The imids immunomodulatory agents
• 18:06or the monoclonal antibodies and
• 18:08this is referred to as a triple,
• 18:10reclass refractory disease,
• 18:11and as you can see here,
• 18:13in addition to isatuximab,
• 18:14there have been four other agents
• 18:17approved over the last two years for
• 18:19the treatment of individuals with.
• 18:21Relapsed or refractory myeloma and this
• 18:23really presents great opportunities
• 18:24and promise for our myeloma patients.
• 18:26And so we'll review each of these
• 18:28medications and in more detail,
• 18:29and we'll have time at the end of our
• 18:33discussion for any questions that come up.
• 18:36So firstly is selinexor which is a
• 18:38small molecule that binds and blocks
• 18:40exportin one and export and one is a
• 18:43protein that's found on myeloma cells
• 18:45that can promote the growth of tumor
• 18:47by removing proteins from the myeloma
• 18:50cells that are meant to suppress the tumor.
• 18:52However,
• 18:53if you see here in the in the
• 18:55figure on the right when selinexor,
• 18:57which is also referred to as selective
• 19:00inhibitor of nuclear export or sign,
• 19:02is bound to this exportin.
• 19:03One.
• 19:04The tumor suppressors can accumulate
• 19:05in the nucleus of the cell and the
• 19:08body then can eliminate tumor cells
• 19:10while preserving normal cells.
• 19:12Selinexor is the first drug in this
• 19:14class of medications and is being
• 19:16studied in other blood cancers as well.
• 19:18In multiple myeloma,
• 19:19selinexor is approved as an oral
• 19:22pill at a dose of 80 milligrams,
• 19:24taken twice per week with the steroid
• 19:26dexamethasone and this is for
• 19:28individuals with relapsed or refractory
• 19:30myeloma who have received at least
• 19:32four prior lines of therapy and are
• 19:34no longer responding to at least two
• 19:36of the pies previously discussed.
• 19:39At least two images and an anti CD.
• 19:4138 monoclonal antibody selinexor
• 19:43is also approved at a dose of
• 19:45100 milligrams once per week with
• 19:47Bortezomib and dexamethasone.
• 19:48For patients,
• 19:49again with three lobster refractory myeloma.
• 19:51But this time,
• 19:52those who have received only at least
• 19:55one prior line of therapy and these
• 19:57approvals are based on the storm and
• 19:59Boston clinical trials, respectively,
• 20:01which we'll talk more about.
• 20:04So the storm clinical trial evaluated
• 20:07122 patients in the US in Europe
• 20:10who had this triple refractory
• 20:12multiple myeloma that I mentioned
• 20:14and had received a median of seven
• 20:16lines of prior treatment.
• 20:18These individuals were given oral selinexor,
• 20:2180 milligrams and dexamethasone 20
• 20:23milligrams, both twice twice a week,
• 20:26and 26% of these patients achieved
• 20:28what doctor bar defined as a partial
• 20:31response or more than 50% improvement
• 20:34in their monoclonal protein.
• 20:36And while 30 and end of this group,
• 20:3939% of patients had at least a
• 20:41minimal response and responses
• 20:42overtime in those patients who did
• 20:44have at least a partial response or
• 20:47seen in the figure here at the left,
• 20:49the median duration of the response
• 20:51or the
• 20:52median time that the response
• 20:54lasted was about 4.4 months.
• 20:56And then the second trial with Selinexor is
• 20:59the multicenter phase three Boston trial,
• 21:01which looked at 402 myeloma patients.
• 21:05That were treated with one to
• 21:07three prior lines of therapy,
• 21:08and these patients were randomly assigned
• 21:10to get either selling X or 100 milligrams
• 21:13once per week combined with Bortezomib.
• 21:15The proteasome inhibitor and dexamethasone.
• 21:17The steroid or Bortezomib and
• 21:19dexamethasone alone and what's shown
• 21:21here in the figure on the right is that
• 21:23the patients who received selinexor,
• 21:25so they sell an extra group,
• 21:27had a longer time without disease.
• 21:29Progression at a median of 13.9 months
• 21:31when compared to the group who only
• 21:34got Bortezomib and dexamethasone.
• 21:36Where the progression at the time
• 21:38without progression was about 9.5 months.
• 21:41The more common side effects observed
• 21:43with selinexor in both of these clinical
• 21:46trials and in practice include fatigue.
• 21:49Gastrointestinal symptoms such as nausea,
• 21:51infections, and low blood counts.
• 21:54Thrombocytopenia or low platelet
• 21:55count in particular,
• 21:57was seen in 73% of patients and storm,
• 21:59although in the Boston trial,
• 22:01even though patients had low platelet counts,
• 22:04they did not have significant bleeding
• 22:06events or complications with bleeding.
• 22:08Notably,
• 22:09the use of anti nausea medication,
• 22:11so medications to try to prevent
• 22:13nausha is really important with
• 22:15selinexor and one specific approach
• 22:17that has been used by our group
• 22:19and others is to give a medication
• 22:22called olanzapine or Zyprexa daily.
• 22:23With treatment to try and prevent
• 22:26the onset of significant nausha.
• 22:28Side effects from selinexor do
• 22:30appear to improve as after initial
• 22:32treatment or as treatment continues
• 22:34and they can be well managed with
• 22:37supportive care and are reversible.
• 22:39If this selinexor is stopped.
• 22:44The next agent will discuss is
• 22:46Bill Lanthanum Alpha Dowtin,
• 22:47which is a medication made up of an
• 22:50antibody that's attached to a drug that's
• 22:53toxic or can kill myeloma cells and as
• 22:56seen in the figure here on the right,
• 22:58it binds what's referred to as B
• 23:01cell maturation antigen ORB may,
• 23:02which is a protein on the surface of
• 23:05myeloma cells that overexpressed.
• 23:07So there's more than than in normal cells,
• 23:10and this allows for delivery
• 23:11of mpid open into the cells.
• 23:14Resulting in interruption or stopping
• 23:16of cell division and myeloma cell death.
• 23:18Blanton on methadone and also
• 23:21improves or enhances the body's own
• 23:23immune spot response are the immunes
• 23:25ability to fight off myeloma cells.
• 23:28Blanton AB is approved as a single agent,
• 23:31a single medication at a dose
• 23:33of 2.5 milligrams per kilogram,
• 23:36which is administered through
• 23:37intravenous infusion.
• 23:38Once every three weeks,
• 23:39and this again is approved for
• 23:42patients with relapsed or refractory.
• 23:44Hi Wilma,
• 23:45who have received at least four
• 23:47prior therapies including Apiai,
• 23:49Imid and an anti CD.
• 23:5138 monoclonal antibody and this
• 23:53is based off effectiveness that
• 23:55was shown in the dream two study.
• 24:01So the dream two trial evaluated
• 24:04this first anti BCMA antibody drug
• 24:06conjugate in 196 patients with
• 24:08relapsed or refractory myeloma who
• 24:11had received at least three lines of
• 24:14treatment prior and were refractory
• 24:16or were no longer responding to the.
• 24:19Again, the three categories of medications
• 24:21we talked about frequently, the P,
• 24:24imid or immunomodulatory agent and an
• 24:26anti CD 38 monoclonal antibody and these
• 24:30patients studies were rent studied.
• 24:32End of my story.
• 24:33See if either a 2.5 milligram
• 24:35per kilogram dose of Balanta map
• 24:38or 3.4 milligrams per kilogram,
• 24:40and this was given intravenous,
• 24:42intravenously or through through
• 24:43an Ivy every three weeks.
• 24:45The overall response rate in
• 24:47the dose that's recommended,
• 24:49which is the 2.5 milligrams per kilogram,
• 24:51was 31%,
• 24:52and 60% of these patients who responded
• 24:55had at least a very good partial response,
• 24:58which is a improvement in the
• 25:00monoclonal protein of more than.
• 25:0290%.
• 25:03Overall response rate was also
• 25:0638.5% in the the population of
• 25:09patients who had higher risk
• 25:11genetic features to their myeloma.
• 25:14And in this population is
• 25:16often a harder to treat,
• 25:18and the median time to response
• 25:20for Balanta map was 1.4 months,
• 25:22with 73% of those patients
• 25:24who achieved a response.
• 25:25Having it maintained at least
• 25:27for six months at the time that
• 25:30this clinical trial was reported.
• 25:32A major category of side effects
• 25:35with with Balanta map or the eye
• 25:37disorders that are listed here
• 25:39and observed in 77% of patients
• 25:41in this clinical trial and mainly
• 25:43the the side effects in regards
• 25:45to eye symptoms are related to
• 25:47changes that happen in the cornea,
• 25:49which is the very front part of
• 25:51our I and these changes are known
• 25:54as keratopathy and the reported
• 25:56frequently within mostly the first two
• 25:58treatment cycles and they may require either.
• 26:01A reduction in dose or
• 26:03holding of the treatment.
• 26:05Learning about these eye symptoms
• 26:07has prompted a requirement for
• 26:09patients with angle antiknock ticket.
• 26:12Regular eye exams for close monitoring
• 26:14and also it's recommended that
• 26:16individuals on this medication
• 26:18use a lubricant.
• 26:19Eye drops regularly and avoid contact lenses.
• 26:23Other potential side effects associated
• 26:25with Blanton Mabor listed here.
• 26:27They include allergic,
• 26:29type or infusion related reactions,
• 26:31infections, and low blood cell counts.
• 26:37So Next up is melphalan Fluphenazine
• 26:39mid or malfouf in and this again
• 26:42is a first in class medication.
• 26:44It's a peptide which is a short chain
• 26:47of amino acids and it's combined
• 26:49with or conjugated to an alkyl
• 26:52later drug similar to the melphalan
• 26:54that we had discussed previously.
• 26:56And what happens is this medication
• 26:59can rapidly enter and be released
• 27:01into myeloma cells,
• 27:02causing irreversible damage
• 27:03to the DNA of the tumor.
• 27:05That's important for two.
• 27:07Or growth and this therefore
• 27:09leads to cell death.
• 27:10Melphalan Fofana Mid is approved
• 27:12at a dose of 40 milligrams.
• 27:14It it two is given by intravenous infusion,
• 27:17but once every four weeks and it's
• 27:19combined with the steroid dexamethasone,
• 27:22which is administered weekly for patients.
• 27:24And again this this approval is
• 27:26for patients with relapsed or
• 27:28refractory multiple myeloma who
• 27:29have received at least four prior
• 27:32therapies and are no longer responding
• 27:34to a PPI image and an anti CD.
• 27:3738 monoclonal.
• 27:37Antibody and this is based off the
• 27:40horizon study melphalan fluphenazine.
• 27:42I'd is a bit unique in that it does
• 27:45require a central catheter for infusion,
• 27:48such as a port or a pick line.
• 27:53So the horizon study was a multicenter
• 27:55trial of a total of 157 patients
• 27:58with relapsed or refractory myeloma.
• 28:00Though the approval was really based on
• 28:02a smaller group of patients in the study
• 28:05who had received at least four prior
• 28:08lines of treatment and were considered
• 28:10or triple class refractory refractory.
• 28:12In this group, the overall response
• 28:14rate was 26% and 9.3% of patients
• 28:17achieved a very good partial response
• 28:19or improvement of more than 90%
• 28:21in their monoclonal protein.
• 28:23The the median time to response
• 28:26was 2.1 months,
• 28:27so it took about 2.1 months for most
• 28:29patients to see a response and the duration
• 28:32of response was about 4.2 response.
• 28:34But 4.2 months there was a
• 28:3615% overall response rate.
• 28:38In patients with what's referred to as
• 28:40extramedullary disease or myeloma disease
• 28:42involving tissues and or organs that
• 28:45are outside the bone or bone marrow,
• 28:47which typically is a high
• 28:49risk feature for myeloma.
• 28:50Side effects observed with melphalan flu.
• 28:53Fenamad included primarily low grade low
• 28:55blood cell counts which were managed
• 28:57appropriately with either reduction
• 28:59in doses of the medication or other
• 29:02supportive care given by providers.
• 29:04Fatigue,
• 29:04swelling,
• 29:04and bone and joint inks also occurred.
• 29:07GI symptoms such as nausea and vomiting,
• 29:10were not severe in the clinical
• 29:12trial and there was no hair loss or
• 29:16neuropathy or numbness and tingling
• 29:18in the extremities or legs or arms.
• 29:20That were reported with the use of
• 29:22melphalan flu femmed in this trial.
• 29:27The last therapy we will discuss
• 29:29is the one most recently approved
• 29:31and this is the chimeric antigen
• 29:34receptor T cell or what is known
• 29:36as CAR T cell therapy idake.
• 29:40Excuse me, I to sell or idake.
• 29:44I do sell Vic Loosle ore Ida Salandit,
• 29:47the brand name forward is referred
• 29:49to as a Beckman.
• 29:51And the way that the car T and
• 29:53this product in particular works
• 29:55is that a patient's own T cell,
• 29:58a type of immune or white blood cell,
• 30:00is genetically modified by adding
• 30:02the chimeric antigen receptor or
• 30:04car that can then bind to the BCMA
• 30:07antigen present on myeloma cells.
• 30:09As previously discussed,
• 30:10there is activation and growth of
• 30:12these reprogrammed T cells which
• 30:13are then able to find and kill
• 30:16myeloma cells through various
• 30:17mechanisms through a variety of ways
• 30:19including release of cytokines.
• 30:21Which are small proteins?
• 30:22Importantly,
• 30:23which are important in inflammatory
• 30:25responses and signaling to cells.
• 30:26Ida Cell is the first car T
• 30:28approved in patients with relapsed
• 30:30or refractory multiple myeloma,
• 30:32and these patients who are eligible
• 30:34to receive it have received at
• 30:37least four prior lines of therapy,
• 30:39which again include AP and image and
• 30:41anti CD 38 monoclonal antibody and.
• 30:44This was based off what is known
• 30:46as the Karma trial and with car
• 30:49T cell therapy there are more.
• 30:51Multiple steps which are required
• 30:53including with Ida cell treatment
• 30:55and this includes blood collection
• 30:57or removal of these T cells through
• 30:59a process called a pheresis.
• 31:01This is followed by the manufacturing
• 31:04or the production of the car T cell
• 31:07product and this usually takes about
• 31:09a four week period and patients
• 31:11receive a low dose chemotherapy
• 31:13before I do cell infusion,
• 31:15usually over three days.
• 31:16And I do cells then administered as an
• 31:20infusion over 30 minutes per infusion bag.
• 31:22Importantly,
• 31:23there is a period of close monitoring
• 31:25after receiving Ida sell as well.
• 31:31So the Karma trial was a multi
• 31:33center phase two trial that included
• 31:35patients who had received at least
• 31:37three prior therapies including Apiai,
• 31:40Imid and an anti CD 38 antibody.
• 31:43Patients received I to sell at
• 31:45different dosages and of the 128
• 31:47patients who received this therapy,
• 31:4973% of them had a response with 33%
• 31:52having achieved a complete response or
• 31:55normalization of their myeloma studies
• 31:57in the blood or urine or better,
• 31:59the responses observed at the various
• 32:01dose levels and in the total group
• 32:04are seen in the figure here with the
• 32:07approved dose for Ida cell now being 300
• 32:10to 450 * 10 to the six Carty positive.
• 32:13Cells the majority of patients who
• 32:16received the approved dose were free
• 32:18of disease progression for 11.1 months
• 32:20and this increased to 20.2 months in
• 32:23those who had achieved what's known
• 32:25as a stringent complete response.
• 32:27With where there's disappearance
• 32:28of the myeloma protein in the blood
• 32:31in urine and no evidence of myeloma
• 32:33and the bone marrow,
• 32:34the most common side effects of
• 32:36this treatment were low blood cell
• 32:38counts and what's referred to as
• 32:40cytokine release syndrome,
• 32:42or the body's response to
• 32:43this uncontrolled and.
• 32:44Really excessive release of these
• 32:47proinflammatory cytokines that we
• 32:49discuss and this can lead to fever,
• 32:51low blood pressure,
• 32:52fast heart rate and low oxygen levels,
• 32:55among other symptoms.
• 32:56Cytokine release syndrome occurred
• 32:58to some degree in 84% of patients at
• 33:01a median of one day after infusion.
• 33:03Those severe events were not very common,
• 33:06and cytokine release syndrome
• 33:07was quickly identified due to the
• 33:09close monitoring and appropriately
• 33:11managed depending on its severity.
• 33:13Neurologic side effects occurred
• 33:15less frequently in this study than
• 33:17with other card T agents.
• 33:21So in addition to these newly approved
• 33:23agents, treatment options for patients
• 33:25with multiple myeloma continue to expand,
• 33:27and this is really through the study
• 33:29of new medications and combinations.
• 33:31On this slide, I've outlined a sampling
• 33:33of our available clinical trials here
• 33:35at Smilow and Yale Cancer Center,
• 33:37which, as you can see,
• 33:39are fortunately available for all time
• 33:41points in the myeloma disease course.
• 33:43So we have a study available
• 33:45for patients with smoldering or
• 33:47asymptomatic multiple myeloma that
• 33:49assesses or evaluates the benefit
• 33:51of adding Derek to map the anti CD
• 33:5338 monoclonal antibody to previously
• 33:55studied Lenalidomide for patients
• 33:57with newly diagnosed multiple myeloma.
• 33:58We we do have an investigator initiated
• 34:01trial led by Doctor Never Eats that is
• 34:04evaluating a more complete assessment
• 34:06of response in myeloma by looking
• 34:08both in the bone marrow and data
• 34:11myeloma bone lesions before and after.
• 34:13Therapy with carfilzomib,
• 34:15Lenalidomide and dexamethasone.
• 34:18And for those patients who are to
• 34:20receive maintenance therapy after
• 34:22undergoing a stem cell transplant
• 34:24but still have evidence of a low
• 34:27level of residual or remaining
• 34:28myeloma disease in the bone marrow,
• 34:31or what Doctor Barr defined
• 34:32as minimal residual disease,
• 34:34we do have a study looking at outcomes
• 34:37of adding again daratumumab to
• 34:39our standard maintenance regimen.
• 34:41For many patients, which is Lenalidomide.
• 34:43And lastly,
• 34:44we have multiple trials for patients
• 34:46with relapsed or refractory myeloma.
• 34:49Including an investigator initiated
• 34:50trial looking at quality of life
• 34:52for patients on daratumumab and
• 34:54trials with new medications,
• 34:55including those that use our patient's
• 34:57own immune system to fight off the
• 35:00myeloma and so at the conclusion of our talk,
• 35:03we'd be happy to share more information
• 35:05to help answer any questions you
• 35:07may have about our clinical trials.
• 35:09And thank you again for your time.
• 35:12I will now turn it over to Tara Anderson.
• 35:22Alright. One second, see.
• 35:40OK. Thank you Sabrina. So I'm Tara Anderson.
• 35:44I'm a physician assistant with the myeloma
• 35:47group here and I've been here since
• 35:492015 and started doing myeloma in 2005
• 35:52and I'm going to talk about the common
• 35:55side effects with the myeloma therapies.
• 35:57The main therapy since the doctor Browning
• 36:00touched on all of the recent approved
• 36:02drugs and all of those side effects.
• 36:05So I'm going to talk about the
• 36:07main classes of medications that
• 36:09Doctor Barr discussed and.
• 36:11The general side effects from each class.
• 36:16Alright, so the different classes of
• 36:18treatment as Doctor Barr discussed
• 36:20in her presentation and then we
• 36:23usually combine as she mentioned,
• 36:25three drugs, or potentially now
• 36:27for drugs and one from each class.
• 36:30So produce some inhibitors,
• 36:32immune modulatory drugs,
• 36:33monoclonal antibodies,
• 36:34and most of our therapies
• 36:36include dexamethasone.
• 36:39So the general side effects that are
• 36:41included in all of our treatments,
• 36:44I just don't want to have to put it
• 36:46in all the slides, so you can always
• 36:49refer back to this slide is fatigue.
• 36:52All of them are transgenic.
• 36:54We know with the imids we always do the
• 36:57Rams program, but all of them should
• 37:00require 2 forms of contraception and.
• 37:03They're all class D for pregnancy,
• 37:06so and all of the medications
• 37:08that we use can cause rashes.
• 37:11So what we typically would do for
• 37:13a rash is use a steroid cream.
• 37:16Or, depending on the how much
• 37:18the rash covers of the body or
• 37:20the symptoms from the rash.
• 37:22Sometimes we'll just do an Anna
• 37:24histamine prior to taking the medication,
• 37:26and if the rash is more severe
• 37:28than we will hold the medication
• 37:31and potentially reduce the dopes.
• 37:33And then all of the treatments
• 37:35also cause decreased blood counts.
• 37:37So with each treatment when you
• 37:39come in for treatment,
• 37:40we check your blood counts to make sure
• 37:43it's safe to go ahead with treatment.
• 37:45And if it's not,
• 37:46sometimes we have to hold the medication,
• 37:49and occasionally we have to reduce the dose.
• 37:51And I and sometimes will also
• 37:53use growth factors like NEUPOGEN
• 37:55to stimulate the bone marrow to
• 37:58help reduce some of those cells.
• 38:00And with the reduced blood counts
• 38:02you can see,
• 38:03I mean a suppression and with all
• 38:05of the treatments that can happen.
• 38:07So we want to make sure you call
• 38:10for any fevers you know.
• 38:12There's always somebody here,
• 38:13so a temperature is considered
• 38:15100.4 or higher,
• 38:16and then if you get frequent infections
• 38:18or hospitalized for several infections,
• 38:20sometimes will talk to you about giving
• 38:22an Ivy called IVIG which is immuno globulin.
• 38:25Which gives you some of the immunoglobulins
• 38:27that you don't normally produce.
• 38:29To help protect you.
• 38:31From getting infections,
• 38:32and we usually do that once a month,
• 38:34so these are the general side effects
• 38:37from all those classes of drugs.
• 38:39And then specifically for the produce
• 38:41some inhibitors which are listed below.
• 38:43I will talk about someone
• 38:44specific just for those,
• 38:45and you can see the dates when
• 38:47these drugs were approved.
• 38:48So I started doing my element 2005 and I
• 38:51can tell you when we started doing it.
• 38:53When I started doing it.
• 38:55The drugs that we use weren't
• 38:56as good as the ones we have now.
• 38:59We saw a lot more side effects and most
• 39:01of these drugs are pretty well tolerated.
• 39:03At least we want them to be.
• 39:05So if you're not tolerating them well then
• 39:08definitely reach out to us so we can.
• 39:10Make it easier for you to tolerate it,
• 39:12because once you're started on treatment,
• 39:15we tend to keep you on therapy for
• 39:17life and want to make sure we can
• 39:19keep the disease under control while
• 39:21maintaining good quality of life.
• 39:26So proteasome inhibitors in general can
• 39:28cause gastrointestinal side effects mildly.
• 39:31Sometimes we hear nausea,
• 39:32vomiting, not commonly,
• 39:34but it can some more than others,
• 39:37as I'll get two with the oral proteasome
• 39:40inhibitor and they all have a risk of
• 39:43reactivating herpes zoster or shingles,
• 39:46so all patients should be on
• 39:49acyclovir as a prophylaxis.
• 39:52And again, referring to the first slide,
• 39:54all those apply as well.
• 39:57And then both them up or VELCADE.
• 39:59One of the most common side effects we
• 40:00see with that is peripheral neuropathy.
• 40:03We would see it a lot more when we
• 40:05did give Velcade Ivy and we used to
• 40:07give allocate twice a week and now
• 40:09that we give it in a subcutaneous
• 40:11form and typically we give it weekly.
• 40:13We see a lot less neuropathy,
• 40:15but we still see it.
• 40:16So the key is to get a baseline
• 40:18assessment to see if anybody has any
• 40:20numbness or tingling in their hands
• 40:22and feet is typically where we see
• 40:24it at baseline and then to monitor
• 40:26to make sure it's not getting.
• 40:28Worse,
• 40:28we want to make sure it's not painful
• 40:30and it's not interfering with daily
• 40:32functioning like buttoning buttons
• 40:34or holding on to a coffee cup,
• 40:36or those types of things.
• 40:38And if it does then we may have to
• 40:41hold it or lower the dose and most of
• 40:44the time in 70% of patients it's reversible,
• 40:46so the key is to communicate with us
• 40:49when you have the neuropathy so we can,
• 40:51you know,
• 40:52make it better,
• 40:53and then we can also use these medications.
• 40:56Gabapentin,
• 40:56Lyrica or Cymbalta which sometimes.
• 40:58Help with neuropathy?
• 41:01We can also lower blood pressure,
• 41:03so if you're on blood pressure
• 41:05medication sometimes will have
• 41:07to hold it during the time when
• 41:08you're getting the VELCADE,
• 41:10and this isn't really a side effect
• 41:12but just kind of a note that if
• 41:14we take them in C supplements,
• 41:16we should hold it because there
• 41:18is data showing that vitamin C can
• 41:20interfere with the efficacy of alkane.
• 41:25Carfilzomib so the main thing
• 41:26with carfilzomib is the cardiac
• 41:28toxicities and the key here is also
• 41:30getting a baseline assessment.
• 41:31So if you have hypertension to get
• 41:34it controlled before we get started
• 41:36with the treatment and then to
• 41:38monitor it throughout and then we
• 41:40also want to make sure the hearts
• 41:42functioning OK so we'll do an echo.
• 41:44So an ultrasound of the heart prior to
• 41:47starting typically and we usually do an
• 41:49EKG and then a BNP as a as a blood draw.
• 41:52The lab that looks at the.
• 41:55Nonspecific marker of the
• 41:56stress on the heart.
• 41:58So we monitor that monthly.
• 41:59And then we want you to watch out for
• 42:02any kind of swelling in your legs,
• 42:05shortness of breath.
• 42:06Abdominal distention, because some of
• 42:08those could indicate that the heart isn't
• 42:11pumping as effectively as it should,
• 42:13so we watch for those.
• 42:15It's a low percentage,
• 42:17but it does happen so.
• 42:19We monitor those monthly as well.
• 42:22And because it's given Ivy,
• 42:24we sometimes see inflammation of
• 42:25the vein or thrombophlebitis,
• 42:27and you can use ice and that
• 42:29should help Tylenol.
• 42:31But if it keeps happening sometimes we
• 42:33recommend to use support and occasionally
• 42:35we can see pulmonary hypertension.
• 42:37So sometimes the shortness of
• 42:39breath may not be due to the.
• 42:42The heart,
• 42:43but it may be more due to the lungs,
• 42:45so we can usually pick that up on an echo.
• 42:48Or if we can't figure out
• 42:49what's going on with the heart,
• 42:51sometimes will refer to a pulmonary doctor.
• 42:55And then examine or narrow is the
• 42:57last produce I'm going to have better
• 43:00that was approved and it's oral.
• 43:01So because it's oral we see a lot
• 43:04more GI side effects or in the data.
• 43:06And in all the trials they see
• 43:08a lot more jet GI side effects.
• 43:10I think in practice we don't see as many,
• 43:13but we usually tell you to have Zofran
• 43:15or Imodium on hand just in case,
• 43:17and then obviously if you were to
• 43:20vomit after taking the pill we won't
• 43:22want you to reach, you know take the
• 43:24pill again 'cause we don't know.
• 43:26How much was absorbed?
• 43:28And also reach out to us if
• 43:30that was to happen.
• 43:32You can also see lower extremity
• 43:34swelling with this one.
• 43:36We recommend compression stockings,
• 43:38elevating your legs and sometimes
• 43:40will give you a water pill or lay 6.
• 43:46OK, and the second class of medications
• 43:48that we use in combination or the
• 43:51immunomodulatory drugs or image.
• 43:53So the first one that was
• 43:55approved was the Little Mide
• 43:57and that was approved in 2006,
• 44:00but we were using it earlier
• 44:02and kind of off label,
• 44:04and we don't use it as much because it
• 44:07has more toxicities and the other two.
• 44:10So now we typically start with
• 44:13Lenalidomide or REVLIMID and
• 44:14then after relapse, use POMALYST.
• 44:19So in general, that emits are
• 44:21putting patients at higher
• 44:22risk of venous thromboembolism.
• 44:24So we don't want so blood clot.
• 44:26So we want you to let us know if you
• 44:29had any swelling in your legs or pain
• 44:32and your legs or shortness of breath.
• 44:35And we put you on an aspirin
• 44:37as prophylaxis, typically.
• 44:38Or if you if you're at high risk
• 44:41or have had a thought before,
• 44:43we usually place you on an
• 44:45oral anticoagulant now.
• 44:46In the past we use Lovenox or Coumadin.
• 44:49And now we have the newer agents which
• 44:52are easier to use the oral anticoagulants.
• 44:55And then I know I brought up the terror
• 44:58that regeneca effects in general,
• 45:00but with this one we have to do the
• 45:03Rams paperwork and you have to do the
• 45:06phone surveys and so just a reminder
• 45:08with that way back in the 50s and
• 45:1160s the limit was used as a sleeping
• 45:13pill for pregnant women and then
• 45:15they had babies that were had deformity.
• 45:18So that's why the REMS program
• 45:20is in place with that drug.
• 45:25So Speaking of full time,
• 45:26I'd the main side effects that we
• 45:29see are fatigue, Constipation,
• 45:30numbness and tingling.
• 45:31So those are the top three and then also
• 45:35we can see a slowed heart rate with it,
• 45:37which may be causing some other fatigue.
• 45:41We typically used it at lower
• 45:42doses when I was using this,
• 45:44when there wasn't much else to use,
• 45:46we would use much higher doses and it was
• 45:49very difficult to tolerate at that time.
• 45:51But with the lower doses we can usually.
• 45:55Use it with minimal side effects and
• 45:57some of these medications to help so
• 45:59the same with them with the numbness
• 46:01and tingling in the gabapentin,
• 46:03Lyrica, and Cymbalta.
• 46:05And the typical things we we want
• 46:08you to do if you're constipated,
• 46:10so Senate police increased water fiber.
• 46:13Those types of things.
• 46:17And then learn a little made one of them
• 46:19are common side effects as diarrhea,
• 46:22especially the longer you're on.
• 46:23It tends to be more of a cumulative
• 46:26effect and we do different things.
• 46:28First, we want to make sure that
• 46:30you're not having diarrhea from a,
• 46:32you know a different cause like infection.
• 46:35Or, you know, is it you know,
• 46:37did you develop an intolerance to
• 46:39lactose or something like that?
• 46:41Or high fat foods?
• 46:42So sometimes will alter the diet.
• 46:44Try Imodium,
• 46:45and if those don't work,
• 46:46sometimes will add a medication called
• 46:48full listed which helps with the
• 46:50diarrhea associated with Lenalidomide.
• 46:52And then I put trash in here,
• 46:54even though we already talked about it,
• 46:56because it's fairly common with Lenalidomide,
• 46:58and again,
• 46:59a lot of times we have to hold and reduce the
• 47:02dose if the creams and the Anna histamines.
• 47:05Aren't controlling the rash?
• 47:08And then if you second primary
• 47:10malignancies can happen,
• 47:12this is because people are living
• 47:14longer and doing better with myeloma.
• 47:16On this for a long time.
• 47:19And they've seen second primary malignancies.
• 47:22So just a reminder to follow up with
• 47:25your primary care for routine screenings.
• 47:27Definitely the the benefits of the
• 47:30Lenalidomide Lenalidomide outweigh the
• 47:31risk of these second primary malignancies,
• 47:33but it's still something to be cautious
• 47:36of and follow up with your primary care.
• 47:40And then the last images,
• 47:42comma,
• 47:42little mid and again rash is
• 47:44fairly common with this one and the
• 47:46only other one we see peripheral
• 47:48neuropathy occasionally with this
• 47:50not as much as with the little mine,
• 47:52but otherwise it's fairly well tolerated.
• 47:54We don't usually see as many GI side effects.
• 47:57We tend to see a little bit more
• 48:00cytopenia or low blood counts.
• 48:02Mainly because it's used later in therapy.
• 48:07OK, and then the last class of
• 48:10medications or the monoclonal antibodies.
• 48:13So there's three.
• 48:14There are two memebr and ilities
• 48:17map were both approved in 2015 and
• 48:20then just last year daratumumab was
• 48:23approved subcutaneously and then.
• 48:26It's a text map,
• 48:27is just approved last year,
• 48:29so these have made a big
• 48:31difference and treatment,
• 48:32and they're fairly well tolerated.
• 48:34And now that we have
• 48:35daratumumab subcutaneous,
• 48:36it's made a big difference and some
• 48:38other patients that have had Ivy
• 48:40know that the first time we give it.
• 48:43It's like an all day infusion and
• 48:45then the next is like half a day.
• 48:47So it was a long.
• 48:49There are long days and now that
• 48:51we can give it subcutaneously,
• 48:53it's a lot shorter.
• 48:54It's about a 10 minute injection.
• 48:57And you only have to stay for a few
• 48:59hours after the first injection.
• 49:01So our main concern with these
• 49:04medications are the infusion
• 49:05related reactions and we typically
• 49:08would only see a reaction with the
• 49:11first injection or first infusion.
• 49:13But as you can see the the reactions
• 49:16are fairly common marso with Dara.
• 49:19I've eaten subq, it's 34 to 48%.
• 49:23Well,
• 49:23at last with the subcu and then it's a text.
• 49:27Matt is similar to the Dara and
• 49:29the E Lo is only about 10%.
• 49:32So to prevent these infusion
• 49:34reactions we premedicate with Tylenol,
• 49:36Benadryl and dexamethasone and
• 49:37with the first infusion we also
• 49:39give singular for Dara.
• 49:41And we give Pepcid for acid attacks in men.
• 49:45And this and we give this with
• 49:47each infusion the singular we
• 49:48only do with the first infusion,
• 49:49and this tends to reduce the rate.
• 49:52And most of the infusion reactions
• 49:55are very mild. We just stopped.
• 49:57Infusion treat the reaction and
• 49:59then we started at a lower dose.
• 50:02So we just want to make sure you
• 50:04let the nurse know if you notice
• 50:06anything like scratchy throat,
• 50:08cold,
• 50:08nauseous to let the nurse know
• 50:10right away so we can stop the
• 50:13infusion and treat the reaction.
• 50:15And then we also see shingles
• 50:17with monoclonal antibodies.
• 50:18So you need to be on prophylaxis with
• 50:21acyclovir with this one as well,
• 50:23and then the studies that are
• 50:25increased risk rates of an
• 50:27upper respiratory infections.
• 50:30And then the fast, the last one is steroids.
• 50:34Everyones favorite dexamethasone.
• 50:35So this one is probably the hardest to
• 50:38tolerate just because of you know the weight.
• 50:40Gain the irritability.
• 50:41All these things that
• 50:43happened and trouble sleeping.
• 50:44So sometimes will give melatonin or
• 50:46atterax which is a older generation
• 50:49antihistamine and we may have to reduce
• 50:51the dose if there's lots of side effects,
• 50:54and then you should be following up with an
• 50:57eye doctor 'cause it can cause cataracts.
• 51:00And primary care under friend
• 51:03'cause you can see steroid
• 51:05induced steroid induced diabetes.
• 51:08Excuse me
• 51:11alright. So in summary,
• 51:13treatment for myeloma is generally
• 51:16well tolerated now with a lot a lot
• 51:19better and the like since 2005.
• 51:21Prior to 2005. I think it was,
• 51:24you know, more of the traditional
• 51:26chemotherapy with hair loss, nausea,
• 51:28vomiting, a lot of a lot more toxicity.
• 51:31So with the newer generation of all
• 51:34the different classes we have now,
• 51:37that treatment should be
• 51:38pretty well tolerated.
• 51:40So the key is communication.
• 51:42Make sure you let us know if
• 51:44you're having any side effects
• 51:45so we can adjust it and get the
• 51:48best treatment to help improve.
• 51:50The disease and also we want to
• 51:52get a good baseline assessment
• 51:54to make sure the side effects
• 51:57are coming from the medication.
• 52:00And not something else.
• 52:03So I need a good doctor patient team.
• 52:07Relationship. OK, and then these are just
• 52:10resources for you to look up different
• 52:12side effects and different information.
• 52:15So MRF is a good website and then the
• 52:17multiple myeloma support group meets
• 52:19every the last Tuesday of every month.
• 52:22And then I just put in their
• 52:25their phone number and.
• 52:26The contact information if
• 52:27anybody's interested in.
• 52:28I know it's zoom now because because
• 52:30of kovit I don't know if they're
• 52:33planning to go back to in person, but.
• 52:37That is another place.
• 52:39And that's it, I think.
• 53:01So thank you to Doctor Barr and
• 53:04Doctor Browning and Terra for this.
• 53:06Great talks and presentations.
• 53:07Very educational.
• 53:08I think we have a few questions
• 53:11in both the chat and the Q&A.
• 53:14And. I believe, UM, the.
• 53:17There's a few actually discussing whether
• 53:20or not these slides would be made available,
• 53:23and the video of presentation will be
• 53:25posted at the yalecancercenter.org website,
• 53:28and a copy of the slides can be requested
• 53:31by emailing cancer answers at yale.edu,
• 53:34Her Emily, which we can hopefully if
• 53:37Emily maybe you could put that in
• 53:40the chat box for everyone if they
• 53:43were interested in obtaining a copy.
• 53:46I think that answers to our questions on
• 53:49our chat and one of the first questions
• 53:52that we had and that maybe Doctor
• 53:55Barkin answer was regarding where a
• 53:58Lam Lloyd fit on the spectrum of EM guys,
• 54:02to my Lomax, sure.
• 54:03So
• 54:04that's a very good question.
• 54:07It can fit on any of that spectrum actually.
• 54:11So anytime you have, UM,
• 54:12a cell or plasma cell,
• 54:14even the B cell conflicts of lymphomas.
• 54:17So creating these proteins
• 54:19specifically these light chains
• 54:20they can deposit into organs,
• 54:22and there's no way to predict which which
• 54:25patient or which condition will lead amyloid.
• 54:28It's something about the nature
• 54:30of this protein that leads to the
• 54:32deposition into different organs,
• 54:34and that's what Emily is right?
• 54:36So you can get it.
• 54:38With us you can get a smoldering
• 54:40and you can get it in the same
• 54:43time that you have myeloma,
• 54:44so this is something we as
• 54:46physicians I think about and UM,
• 54:48no ask you questions that make us,
• 54:51UM, you to screen for these things.
• 54:53Ask you questions that if if it
• 54:55is positive that makes us think we
• 54:57should I look deeper into whether
• 54:59there is amyloid deposition.
• 55:00So it's a good question.
• 55:08OK, uh, thanks no Friday.
• 55:10I do believe Emily posted in the
• 55:13chat now where the slides could be
• 55:16obtained if he would like her copy.
• 55:19And we had a few questions.
• 55:21Then over in the Q&A that
• 55:24whoever wants to tag,
• 55:25take a stab at them regarding the
• 55:28effectiveness of the COVID vaccine
• 55:30for our multiple myeloma patients,
• 55:32and what precautions should someone
• 55:34still be taking either around other
• 55:37vaccinated or unvaccinated individuals?
• 55:39So I don't know who wants
• 55:41to brave the COVID world.
• 55:43I can answer that one, so I think it's
• 55:46obviously a very important question,
• 55:48and I think you know we're learning more
• 55:52about it as time goes on, you know,
• 55:55I think studies have suggested that
• 55:57patients myeloma patients on a treatment,
• 55:59and patients with other blood
• 56:01disorders may have less of a response
• 56:04to our available COVID vaccines.
• 56:06You know. Fortunately,
• 56:07the COVID vaccine start at a high level,
• 56:10very high level of effectiveness,
• 56:12and so our recommendation
• 56:14to our myeloma patients.
• 56:16Is still to get the vaccine,
• 56:18but I think it is important to know that
• 56:21that maintaining preventative measures like.
• 56:25Mask wearing and good hand
• 56:26washing and avoiding sick people.
• 56:28It's probably more important
• 56:29in our in our myeloma patients
• 56:31and the general population,
• 56:33so I would recommend that all my lower
• 56:35patients get the vaccine as soon as possible.
• 56:38If they have not already,
• 56:39but continue to practice
• 56:41measures to try to avoid COVID.
• 56:46And and I
• 56:47would add to that that there were
• 56:48a couple of recent publications
• 56:50about myeloma patients and their
• 56:52response to the vaccinations.
• 56:54And yes, it is evident that the
• 56:57antibody production may be lower,
• 56:58like 50% of what you might
• 57:01get in healthier population.
• 57:02But there are also very significant
• 57:04cell responses in their immune cells,
• 57:06T cells and some of the T cells
• 57:09and B cell responses and.
• 57:11And that's what provides protection to
• 57:13model of patients after vaccination.
• 57:18Yeah, I think to follow
• 57:20up on that and the group
• 57:22at Mount Sinai published some
• 57:24of their findings just recently.
• 57:26Actually, on the 28th of this month
• 57:29and they had looked at 320 individuals
• 57:31who had had the COVID vaccine,
• 57:34260 of them received either the Pfizer,
• 57:37the Moderna, so the two dose and
• 57:39what they had shown was about 16%.
• 57:42Fifteen point.
• 57:438% of patients did not mount any detectable
• 57:46antibodies compared to the other 84.
• 57:48Your dad, but that response was
• 57:50very variable and they did find
• 57:53that patients who had had COVID
• 57:55prior to being vaccinated had
• 57:57a higher immune response.
• 57:58Tattoo that.
• 58:01OK, and we have some other questions.
• 58:04I think 2 regarding acyclovir are
• 58:06and whether or not an individual
• 58:07could stop acyclovir if they had
• 58:09received the shingles vaccine.
• 58:11So I don't know if Terra if you want
• 58:13to address that under side effects.
• 58:16Yeah sure I meant
• 58:17to say that actually no.
• 58:19I mean, if you had the shingles vaccine,
• 58:22you still need to stay on acyclovir.
• 58:24If you're getting a monoclonal
• 58:26antibody or producing inhibitor,
• 58:27sometimes we will stop the if you're
• 58:29just on an image for maintenance.
• 58:31You can you can stop the acyclovir,
• 58:33but otherwise you need to stay
• 58:35on it regardless of the vaccine.
• 58:44OK. Uh, we have a few questions coming
• 58:47in and about Carty and transplants.
• 58:51And so maybe Doctor Power
• 58:53you can handle some of these.
• 58:55Someone is asking whether or not there's
• 58:58hospitalization involved with Carty,
• 59:00and if So what is that duration? Yes,
• 59:05so there is hospitalization
• 59:06involved with car T therapy,
• 59:08and that's really to
• 59:10follow on the side effect.
• 59:11Expected side effects,
• 59:12which are this side that kind of lease
• 59:15which majority of patients do get
• 59:17and then potentially even neurotoxicity.
• 59:20So at least seven days but sometimes
• 59:23longer really depends on how you do.
• 59:28OK, great and another question
• 59:30that's coming in regarding on stem
• 59:32cell transplant and side effects.
• 59:34As a questioning at about the
• 59:37malignancies that we should be
• 59:39looking out for following a stem
• 59:41cell transplant and use of REVLIMID
• 59:44maintenance so I don't know if
• 59:46either Natalia know first Sabrina
• 59:48would like to answer one of that.
• 59:52I can respond to that.
• 59:55I can respond to that Terry.
• 59:57So in the studies with REVLIMID
• 59:59or Lenalidomide maintenance,
• 01:00:01there was a slight increase in the absolute
• 01:00:04risk of developing second primary cancers,
• 01:00:07and there was approximately
• 01:00:083% absolute increase risk,
• 01:00:10so the risk is very small,
• 01:00:12and the types of cancers that were
• 01:00:15observed or mostly another blood related
• 01:00:17malignancy or bone marrow malignancy.
• 01:00:20There were a few cases of non
• 01:00:23Hodgkin lymphoma, leukemia,
• 01:00:24myelodysplastic syndrome.
• 01:00:25These were.
• 01:00:26Types of bone marrow cancers that
• 01:00:28developed overtime in among those
• 01:00:30observed on the trials there.
• 01:00:32But there were also several
• 01:00:34solid tumors as well,
• 01:00:35and this is what we see in our practice.
• 01:00:39So the conclusion is that
• 01:00:41majority of the second primary
• 01:00:43cancers would be blood related,
• 01:00:45but overall absolute increased
• 01:00:47risk of secondary cancers is
• 01:00:49on the order of two to 3%,
• 01:00:51so the risk is small and the benefits
• 01:00:54certainly outweighs benefits a benefit.
• 01:00:56A problem in prolonging
• 01:00:57survival awhile and maintenance
• 01:00:59therapy outweighs that risk.
• 01:01:04Great thank you Natalia. Does anyone
• 01:01:06have anything else to add on that?
• 01:01:10And if not, we'll move on
• 01:01:13to another question is,
• 01:01:14as far as if an individual has a medical
• 01:01:17officer of undetermined significance
• 01:01:19for an extended period of time,
• 01:01:21what is the likelihood to remain at that?
• 01:01:24I'm guess level versus risk
• 01:01:26of transformation to myeloma.
• 01:01:30I can answer that so you know,
• 01:01:32come with them guys. As I mentioned,
• 01:01:35the risk of progression is 1% per year,
• 01:01:37but this is an average and there's
• 01:01:39actually other markers we look
• 01:01:41at to assess the risk of M gusts.
• 01:01:43These are things like elevated light chains.
• 01:01:46UM, the amount of protein,
• 01:01:47the monoclonal protein, and I'd say yes,
• 01:01:50time does give us some information, right?
• 01:01:52If someone said M ghosts and everything
• 01:01:54is completely stable for five years,
• 01:01:56that is informative.
• 01:01:57And in in actually smaller in world,
• 01:01:59we know as we.
• 01:02:00Go, you know,
• 01:02:02as we follow patients overtime that 10%
• 01:02:04risk does go down after five years or so.
• 01:02:07If there is no progression.
• 01:02:09So so yes, time is important,
• 01:02:11but it gives us information about
• 01:02:14the behavior for disease.
• 01:02:17Great so I love that line of questions.
• 01:02:20We did have some questions that had
• 01:02:22come in before the presentations
• 01:02:24and those were dealing with
• 01:02:26smoldering myeloma specifically.
• 01:02:28If there's anything in individual can
• 01:02:30do to help prevent the progression
• 01:02:32of smoldering to multiple myeloma?
• 01:02:34If So what does that look like
• 01:02:36and what treatments are available
• 01:02:38for small joint individual?
• 01:02:40I know Doctor Browning you had
• 01:02:42mentioned that there are some trials,
• 01:02:44so would you mind enlightening
• 01:02:46us on smoldering myeloma?
• 01:02:48Sure, absolutely.
• 01:02:49So similar to our approach with an M Gus.
• 01:02:52When we look at somebody
• 01:02:54with smoldering myeloma,
• 01:02:55we want to understand their risk
• 01:02:57and you know, we we do that by
• 01:03:00looking at a couple of things.
• 01:03:02The percentage of a plasma cells
• 01:03:04that are in the bone marrow as
• 01:03:07well as the size of the protein
• 01:03:10in the blood and the size of or
• 01:03:12the amount of free light chains
• 01:03:14that we see in the blood as well.
• 01:03:17And patients who fall.
• 01:03:19Uh, into the intermediate or higher
• 01:03:22risk category for smoldering myeloma.
• 01:03:24There has been evidence that earlier
• 01:03:27treatment with the medication,
• 01:03:29Lenalidomide has been helpful now,
• 01:03:32as occurred.
• 01:03:33Doctor Parker stated,
• 01:03:34there are more trials looking at
• 01:03:37either additions to Lenalidomide
• 01:03:39or other combinations of therapies
• 01:03:42and their effectiveness in
• 01:03:45preventing progression too.
• 01:03:47End organ dysfunction in patients
• 01:03:48who have smoldering myeloma.
• 01:03:49So to answer the first question,
• 01:03:51you know,
• 01:03:52I don't think there's anything
• 01:03:54in particular that individuals
• 01:03:55can can do you know?
• 01:03:56I think when we get this question,
• 01:03:59you know maintaining a healthy diet
• 01:04:00and physical activity is important.
• 01:04:02But but really,
• 01:04:03it depends on kind of the the
• 01:04:05risk of the smoldering myeloma
• 01:04:07and how it progresses overtime.
• 01:04:12I think there was
• 01:04:13a question on the generic Lenalidomide.
• 01:04:17Yeah, and I think there's none that
• 01:04:20are currently available for the
• 01:04:22United States as an approved use.
• 01:04:24As you know, the REVLIMID slash
• 01:04:26Lenalidomide produced by Celgene is
• 01:04:28currently off the label of the patent,
• 01:04:31meaning the patent has expired,
• 01:04:33but unfortunately,
• 01:04:33the price of the drug has not been reduced
• 01:04:37across the world in Europe and Asia.
• 01:04:39There are several similar drugs
• 01:04:41you may call them biosimilars,
• 01:04:43or the generics of these emit medications.
• 01:04:46Lenalidomide or pomalidomide,
• 01:04:47and these are produced in various
• 01:04:50parts of Europe and Asia.
• 01:04:52So, for instance,
• 01:04:53you may hear people using Indian when a
• 01:04:56little mind and similar drugs and and
• 01:04:59they appear to be just as effective.
• 01:05:01I think there there were some of the
• 01:05:04studies coming out of Asia that that
• 01:05:07showed efficacy that's kind of equivalent,
• 01:05:10so. But uhm.
• 01:05:13I'm not aware of the approved US use.
• 01:05:21OK, and then one more that's in the chat
• 01:05:24and then we can go to another one that
• 01:05:27was submitted ahead of time is do the
• 01:05:30panelists recommend patients having their
• 01:05:33cells sequenced or and next generation
• 01:05:35sequencing done to look for targeted
• 01:05:37treatment or for personalized medicine?
• 01:05:39And so maybe we can go around having having
• 01:05:42each of the panelists answer that question.
• 01:05:48Sorry, I think that's a very interesting
• 01:05:50question and under you know, uh, the right?
• 01:05:53UM study where you can use this
• 01:05:55information to guide treatment.
• 01:05:57I think it's very useful. It's not,
• 01:06:00it's not something that's routinely done.
• 01:06:02It's not an FDA approved, UM.
• 01:06:05A way to do things,
• 01:06:07but I think it's in the research world.
• 01:06:09I would recommend it.
• 01:06:13Yeah, I would agree with that I.
• 01:06:16I think it's not a part
• 01:06:18of our standard practice,
• 01:06:19but I think there's a lot to learn
• 01:06:21from that and and I agree that no
• 01:06:24incorporation of that into clinical
• 01:06:26trials moving forward is important
• 01:06:28and I think will be enlightening and
• 01:06:30how to best guide our our treatments.
• 01:06:33As you saw, for patients who have
• 01:06:35relapsed or refractory disease,
• 01:06:36we now have a whole number of treatments,
• 01:06:39but understanding the sequencing of what
• 01:06:41to use first you know is is a challenge.
• 01:06:44And I think understanding more about
• 01:06:47you know the specifics of each patient.
• 01:06:49My Loma may help that.
• 01:06:55I don't have money.
• 01:06:56I don't have much to add to
• 01:06:58that. I mean, I think it's been
• 01:07:00it's been around for awhile.
• 01:07:01Just having it has not been approved but
• 01:07:03it would be great if we could do that.
• 01:07:05'cause there's so many different
• 01:07:07presentations of myeloma.
• 01:07:07If we could know how to target different,
• 01:07:09you know, specific patients that
• 01:07:11have different mutations and things,
• 01:07:12but I don't know how far they
• 01:07:14are like getting this approved.
• 01:07:21Great, so it sounds like more to come
• 01:07:23and then again one last question that
• 01:07:26was submitted ahead of time which was
• 01:07:29dealing with solitary plasmacytomas
• 01:07:31and specifically what is the risk
• 01:07:34of progression to multiple myeloma
• 01:07:36with the solitary plasmacytoma?
• 01:07:39And and so I don't know if Doctor Bar you
• 01:07:42wanna take that or doctor Pepper eats.
• 01:07:50I'm sorry, can you rephrase the question?
• 01:07:53Yes, so the question that was submitted
• 01:07:55was regarding solitary plasma cytoma's
• 01:07:57and risk factors for progression to
• 01:08:00multiple myeloma. So
• 01:08:01in the in some of the largest cohorts
• 01:08:04out of US and European experience says
• 01:08:07it was observed that patients who had
• 01:08:10solitary plasmacytomas either in the
• 01:08:11bone or in other tissues within the
• 01:08:14subsequent follow up after initial
• 01:08:16treatment for the plasmacytoma.
• 01:08:18Approximately 50% of patients did.
• 01:08:20Evolved to develop multiple myeloma in the
• 01:08:23subsequent three to five years of follow up.
• 01:08:26So I think the close follow-up is
• 01:08:29recommended with periodic imaging as to what?
• 01:08:32What are the factors that
• 01:08:34promote that progression?
• 01:08:35I think the Nordic Group had looked at
• 01:08:38some of the angiogenesis risk factors and
• 01:08:41they did not identify many risk factors,
• 01:08:44but there one of them was the badger,
• 01:08:47which is the endothelial blood vessel.
• 01:08:50Type of.
• 01:08:51Inflammatory or angiogenesis mediator,
• 01:08:53but it's not something that
• 01:08:55we routinely test,
• 01:08:57and there's no other easy ways
• 01:08:59of making that prediction,
• 01:09:01and so they the mainstay of monitoring
• 01:09:03would be just periodic surveillance
• 01:09:05initially at every three months,
• 01:09:08and subsequently at every six month
• 01:09:11interval with updated blood work,
• 01:09:13urine tests all of the usual
• 01:09:15myeloma lab tests,
• 01:09:16which includes certain protein
• 01:09:18electrophoresis like chains and urine,
• 01:09:20protein electrophoresis and
• 01:09:22and at least an annual.
• 01:09:24I think nowadays that will be with one
• 01:09:26of the advanced imaging modalities,
• 01:09:29like either a PET scan or low dose CT scan,
• 01:09:33or alternatively MRI of the
• 01:09:35body where it's available.
• 01:09:41Great, thank you.
• 01:09:42So those were all of our pre
• 01:09:44submitted questions and I don't see
• 01:09:46any additional ones in the QA or chat.
• 01:09:49So if anyone has any last minute
• 01:09:51questions please submit those now.
• 01:09:53If not but we can wipe things as down
• 01:09:56and thank you all for your attention
• 01:09:58and thank you to all the panelists.
• 01:10:03Thank you very much everybody.
• 01:10:05Great talks everyone.
• 01:10:09Thanks for joining. Bye.