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A living library of credible information for patients of multiple myeloma and their caregivers.
I'm Dr. Jam Kattari and I'm Dr. Sally
Moore and this is a Myeloma Minutes, a
podcast for people affected by myeloma, patients, friends
and family.
Good morning, Sally.
How are you?
Nice to see you.
Yeah, you too.
Ah, Jam, I'm a bit tired.
I don't know if anyone is ever going
to see the visuals of recording today, Jam,
but my God, the bags under my eyes,
they're worse than normal.
We've got quite a lot going on and
IMS was a busy old time, wasn't it?
So it's like catching up from that, really.
But yeah, otherwise, no complaints.
So thank you for asking.
How are you?
Yeah, good.
So we've just got back from the International
Myeloma Society meeting in Glasgow, which is the
first time it's been in the UK since
the first ever one, which was in 1987.
I think everyone got into the history a
bit, didn't they?
So apparently only like 30 people were at
the first one.
It was not far from where I do
my NHS work at Blenheim Palace.
I mean, the field has moved remarkably, but
you know what's amazing, Sally, just going through
some of the notes of the first meeting,
they were talking about high dose melphalan and
stem cell transplants.
It was just kind of coming into being
years later, decades later.
It's still an important treatment.
Did you enjoy the meeting?
I did.
I mean, it wasn't in a palace, but
it was pretty good, wasn't it?
It wasn't in a palace, but Glasgow is
beautiful, very friendly people.
Yeah, it was really fun.
I mean, so much of this is about
sort of continuing to be inspired and networking,
isn't it really?
Because those networks really produce amazing things.
And I think that's why the field has
progressed so much.
But it is striking, isn't it?
I mean, I think, yes, it's incredible that
transplant was just being discussed at the first
meeting, and we're going to talk about it
a lot today, aren't we?
But it's also amazing how much things have
improved.
Now, you'd expect a degree of improvement because
life has improved for us all generally, hopefully.
I really think myeloma has outstripped the odds.
If you're a betting person, I think what
we're about to share today, you would not
have predicted we would be talking about a
couple of years ago.
I mean, it was great to hear the
updates from IMS about what the new offering
is really for our younger patients who are
having a transplant.
And that's what we're going to speak about
today.
Indeed, we are.
And actually, this links into a lot of
our old pods as well.
So, pods that we've done over the last
year and a half on subjects like steroids
and transplant and neuropathy and maintenance treatment and
monitoring of MRD, minimal residual disease.
So, there are many themes that we've talked
about over the last year and a half
that sort of come together in the subject
that we're discussing today.
But let's just do a recap on all
those areas, hey, Jan, for our listeners, because
there will be some people listening to this
podcast, we hope, who will be about to
start on this pathway and may not have
caught up with the 40 episodes we've done
so far.
And it's always good to do a refresh,
isn't it?
So, I think that's where we're going to
go today.
Yeah, no, it is.
And if you have just been diagnosed with
myeloma and you're going to be starting on
this treatment approach we're going to talk about
today, our aim and your clinician's aim is
to get your myeloma to an undetectably low
level for as long as possible.
The best way to do that is with
this combination of treatments that we're going to
talk about today and they're in broad blocks.
We talk about induction treatment, which is around
16 weeks of chemotherapy, then stem cell collection.
You have to move stem cells from your
bone marrow into your blood and then they're
collected and frozen.
Then you have a stem cell transplant.
Then you recover from that and then you
have a further eight weeks of chemotherapy, which
is called consolidation.
And generally, that's the same treatment that you
had at the beginning and then you have
maintenance treatment.
Now, there's lots of nuance along the way
with all of that, but that is the
way to hopefully get your myeloma down to
an undetectably low level and keep it there.
Yeah, absolutely.
So, the undetectably low level is what we
call MRD.
This trial that was shared at the meeting
basically was exploring if you use four drugs
instead of three at the very beginning and
then after the transplant and then you add
an extra drug to the maintenance, do you
fare better?
Compared to what we're really offering, particularly patients
in the NHS at the moment, particularly that
maintenance piece.
And it showed these incredible results, didn't it?
In terms of that deep, deep remission, so
that's those very low MRD levels, meaning that
if you did a bone marrow on someone
and you tried to find a myeloma cell,
you may not be able to find a
myeloma cell in every 100,000 cells you
looked at, a million cells you looked at.
And what's so important about that point is
we know that if you can't find it
when you've looked so hard for it, that
your remission is likely to be longer.
So, the MRD, what we call MRD negativity,
which is where you can't find those cells,
translates into a far longer time for your
myeloma to come back.
And we were updated as to those timelines.
But it's also really important to say, Jam,
isn't it, that these treatments are working so
well now, you can't wait to prove the
point that someone is going to relapse in
a decade or two's time, because it's just
too long to wait.
So, this is one of the first trials
which is actually using this MRD negativity piece
to really inform the sort of projected or
the anticipated, what we call progression-free survival.
So, to predict when the disease might come
back for most people, knowing that that hasn't
happened yet.
Indeed, that's correct, Sally.
So, the trial, the approach is called the
Perseus approach.
And it's a four-drug combination.
Now, we've spoken about a number of four
-drug combinations over the last year and a
half.
And this is a slight variation on what
we do at the moment in the NHS.
Okay, so at the moment, we've used, you
know, the acronym is DBTD, which is four
drugs.
And that's a mixture of an antibody drug
called daratumumab, a type of injection chemotherapy called
ortezomib, dexamethasone, which is the second D, and
the T is thalidomide, which is a type
of immunomodulatory drug.
So, with this new amended approach, the key
change is that the thalidomide is swapped out
for another drug called lenalidomide, but which in
the acronym is R, because when it was
a branded drug, it used to be called
Revlimid.
It does make it sound more complicated than
it is, but it's not DVTD anymore, it's
DVRD.
Okay, so the key thing is we're changing
one drug, but that is an important change.
Really significant change.
The two drugs are from the same family,
but thalidomide was the first kid on the
block and it was bettered by lenalidomide.
And it changes its toxicity profile, so it's
better tolerated, although all these drugs do have
side effects, but it also means it works
better.
And by that, I mean, works for longer
and in more people.
And so when you throw that into a
pretty good combination anyway, all those treatments add
up to a far better outcome.
So, these four drugs are given for 16
weeks initially.
You'll be given the schedule by your doctors
and your pharmacist.
And I think it can be very overwhelming
at the beginning.
It's like, I've got four different drugs, I've
got injections, I've got tablets, I've got various
support medications, but there are a number of
ways to simplify it for you.
But essentially, two of them are tablets.
This lenalidomide drug is a tablet.
It's given for three weeks out of four,
and that's repeated for the first four-week
blocks, which adds up to 16 weeks.
There are two injections.
So, the bortezomib injection is a little injection
under the skin that's given weekly, typically, for
the first 16 weeks.
And there's a bigger injection that goes under
the skin, daratumumab.
This is an antibody drug, which initially is
given weekly, but then after a number of
doses, it goes to every other week.
And then steroids, dexamethasone, is normally given on
the day of the injections and then the
day after.
So, that's broadly how the chemotherapy is given.
And it may be that different parts of
the country, or indeed different parts of the
world, give this slightly differently.
For example, how frequently you get your Velcade,
the Vebit, or the daratumumab.
But really, it doesn't matter.
The magic in this is all of the
drugs together.
Now, it may be, and we've spoken on
previous podcasts, and we can't have a podcast,
Jan, without talking about steroids, can we?
But it may be that some of the
drugs can be stopped by the steroids.
It's quite a lot to take on, all
of this, particularly if you're newly diagnosed and
you're struggling with other problems due to the
myeloma.
And so, it's very, very, very normal for
some of these treatments, particularly the steroids treatments,
actually, to be modified.
So, if that happens, it doesn't mean that
the treatment's not going to work.
It just means it's about getting the dose
right for you as a person so that
you can manage it.
And importantly, stay on the treatment rather than
trying to pursue perfection in terms of, for
example, what was recommended in the trial, but
getting side effects because it doesn't suit you.
And alongside the chemotherapies, there are support medications.
You'll be given a drug called acyclovir to
stop you getting viral infections.
A blood thinner, typically something called apixaban, which
is used to stop blood clots, which is
a risk for lenalidomide.
You'll be given a tablet to protect your
stomach because steroids can sometimes make your stomach
sore.
And some people will also get an extra
antibiotic, which is given on a Monday, Wednesday
and Friday, called cotrimoxazole, which helps prevent a
specific type of infection, which can occasionally happen
in myeloma patients.
But it's also quite a good antibiotic that's
stopping other infections when people start chemotherapy.
And alongside the chemotherapy, you'll have a bone
strengthening medication with calcium and vitamin D.
And certainly don't have a listen to the
bone health pod to really get a full
analysis of that medication and how it works
and the side effects.
Yeah, great overview, Jam.
And again, the supportive medications can differ, can't
they, across the country?
And it's always hard to remember, actually, I
think, anyway, exactly what's going to be in
that bag.
It's a bag so enormous.
But some other things that might be thrown
in there too might include allopurinol, which is
a tablet that we recommend that most people
take at the very beginning of their treatment,
which can keep their kidneys nice and healthy,
prevent a phenomenon called tumour lysis syndrome.
In some places, another antibiotic for 12 weeks
called levofloxacin might be added in as well.
There was a study done a few years
ago, which essentially looked at how much that
reduced your risk of infection and getting really,
you know, potentially on those rare occasions, you
know, stopping people from getting really poorly.
And it appeared to have a gain, but
that's not necessarily standard of care.
So there may be a few extra tablets
in that bag as well.
If you've got any queries or concerns, talk
to your team about it and they'll be
able to tell you exactly what they're for
and why they're needed.
Yeah.
And I think we get, it does sound
overwhelming, right?
We, you know, we've just, you know, reeled
off, you know, a whole bunch of different
chemotherapy drugs, you know, four drugs combined, various
support medications.
You know, often people will come to us
and they say, I don't take any medication
or, you know, I have a little pill
for high blood pressure and it's like, I
can't, you know, I mean, you know, I
don't even like taking paracetamol to be honest.
It is a change.
I think it's about getting into the rhythm
of a regular treatment.
And of course, I think, you know, unfortunately,
you know, a lot of people listening will
have, you know, symptoms because of their myeloma,
pain, fatigue, you know, other issues.
Their kidney's not working.
So actually, you know, the big and important,
of course, carrot is that actually you might
start feeling better really quite quickly because Sally,
what we have seen is when we combine
four drugs like this, you know, the myeloma
can respond, you know, really very quickly to
treatment.
Yeah, definitely.
You make a brilliant point there, Jam, actually.
I think particularly for those of us, and
I think I'm rather like you, Jam, actually,
that's sort of like, oh, I'll just stick
up with something.
I've got a raging fever.
It's fine.
I'll be all right.
But, you know, if one is prone to
that sort of behaviour, all these tablets are
a huge change.
But the really important thing to hold on
to is two things, I would say.
They're there to make you feel better, not
worse.
Yes, they come with side effects.
But in the long run, the aim here
is to get everyone back on their feet,
living their life back to doing what they
need to do.
And the second really important thing to say
is we take them away as time goes
by rather than adding more in.
I mean, there may be things that need
to be chucked in there, like laxatives, for
example, or pain relief and so on and
so forth.
But generally, the load gets lighter as time
goes by.
People feel better.
And the intention of treatment is to get
you better.
Okay, Sal, so if we go into the
side effects more specifically about these chemo drugs,
what might people expect?
Maybe we can ping pong the letters here,
Jam.
So I'll start with the D.
You start with the D.
Absolutely.
So the D is daratumumab.
That's a bit of a mouthful, isn't it,
for everyone to try and remember how to
say.
We call it DARA frequently, just for ease.
This is an injection, as Jam said, that
you have under the skin.
It's actually a protein injection and an antibody
treatment.
And that means that your immune system can
actually sometimes recognize it as going into your
body and sometimes it can react to it.
And by react, I mean, some people, but
this is very small numbers, you know, it's
less than one in 20, even fewer than
that, might feel like they're coming down with
a cold.
The first time they have it, they get
shiver and they get chills and they feel
a little bit poorly.
So to get around that issue, we give
what we call pre-medications, which are treatments
before the daratumumab to reduce that risk.
And if that does happen, you'll be given
additional treatment.
And that tends to occur if somebody is
going to react within the first four to
six hours of that injection.
Even if you react, when you have your
next jab, it's highly, highly unlikely to happen
again.
And if you didn't react first time around,
that's it, you're out of the woods in
that regard.
So that's probably the main thing with daratumumab
in terms of when you receive it.
It goes in generally the injections in the
tummy and there can be some redness around
the injection site.
That's another thing to say.
And in the long term, when you're on
this long term, when you combine it with
the other drugs, it does increase your risk
of infection, particularly chest infections.
But the doctors and the teams looking after
you will know all about that and what
to do about it.
There's one last thing to say about daratumumab
and that is it also can muck up
some blood tests.
And by that, I mean the protein can
interfere with how we analyse your blood if
we think you might need a blood transfusion.
So before you start the daratumumab, we tend
to take a sample.
So the blood bank or the labs have
got that on record so that they can
always refer to that in the future should
there be a problem.
So that's daratumumab.
It's actually very straightforward.
The reaction, like I say, once you've got
your first dose, it's highly unlikely.
The risk of infection is there, but your
team will know about it.
You might get a bit of redness around
the skin and the team will take an
extra blood sample.
Right.
My turn.
The V.
So V is for Velcade, but more typically
known as bortezomib now.
So as I said, this is an injection
that goes under the skin.
It just really takes a few seconds to
give and it's typically given for the first
16 weeks.
So this drug can affect the way nerves
work and it can cause neuropathy and that
can be felt in a number of ways.
So typically people feel it at their extremities,
like especially in their feet initially.
So you may notice tingling or you can't
quite maybe feel your soles properly when you're
walking or hot and cold feels a bit
different.
So it can be quite subtle to start
with and it tends to come on gradually.
It's certainly not something that happens immediately and
you will be asked about these neuropathic like
symptoms every time you get one of these
injections because it is extremely common and the
way to stop getting it back is to
dial back on the injection.
So we reduce the dose and sometimes even
omit the dose if the symptoms are getting
bad.
It can also affect the nerves that control
blood pressure.
So some people can get dizzy sometimes when
they stand, but we've got very good over
the last 15 years using this drug and
we're quite good at minimising the impact.
But as you're going through it, please do
keep reporting these symptoms to your medical team.
It can also cause bowel disturbance.
Some people get diarrhoea and actually occasionally some
people get constipated.
Fatigue is not uncommon and a smaller percentage
of people can get sore eyes as well.
It doesn't happen to a lot, but when
it does happen it can be unfortunately a
little bit problematic.
DVRR.
I work in the West Country.
Occasionally it slips out a bit like that
actually.
So R stands for Revlimid, which is the
older fashion name for lenalidomide.
So the R is actually L, which is
lenalidomide.
Now this is a tablet you take for
three weeks out of every four.
It tends to be well tolerated, but it's
not completely harmless in terms of how it
makes you feel.
I think in particular one side effect to
highlight is how it can affect your tummy
or your gut.
Some people experience a phenomenon called bile salt
malabsorption, which actually to break that down into
something easy to understand is basically diarrhoea.
And it's diarrhoea which is quite hard to
control.
When you need to go, you need to
go.
And that's because lenalidomide can affect how you
absorb the fats in the gut.
And it's very easy if somebody does experience
this to treat it.
They need an extra supplement to help them
absorb those fats and generally the problem then
tends to settle down.
But the other really important thing to say
about this diarrhoea phenomenon is it can occur
any time you start treatment.
So you might be like, well, I've been
on this tablet for six months and I've
been fine.
That doesn't mean that you're not getting bile
salt malabsorption.
So it doesn't necessarily always need to start
at the beginning.
It can occur many months if not years
later.
Lenalidomide, let's call it with a L name,
can also cause a worsening of the neuropathy
you've just spoken about, Germ.
And actually some people do find the Velcade
neuropathy starts at the beginning but the lenalidomide
neuropathy, even when you stop the Velcade, sort
of keeps those symptoms there at a low
level, which is another reason, as you said,
for letting your team know about this so
that if it starts, we can make the
modifications early so that you're not then stuck
with these sort of side effects.
It can also cause blood clots.
So people are routinely given a blood thinner
to prevent lenalidomide-related blood clots.
It can also cause a rash and the
rash actually, where it does occur, can be
pretty problematic.
I've seen a number of patients who've been
like red from head to toe having had
lenalidomide.
That's not going to make you feel well.
That's not only very uncomfortable but actually can
make you quite poorly when that happens.
So if people get a rash and particularly
if it's a widespread rash, we stop the
lenalidomide, we treat the rash and then we
start it again at a far lower level
and then you can gradually increase the dose
and more often than not the rash doesn't
come back but that can occur as well.
And then lenalidomide can cause low blood counts
as can Velcade actually.
It can cause low platelet counts which can
cause bleeding.
And then the last thing to say is,
I think it's the last thing anyway, when
you start lenalidomide, you'll be asked to sign
additional paperwork about pregnancy.
If you're a man, this is still relevant.
If you're 25 years old or 95 years
old, you'll still be asked to complete paperwork
and that paperwork is there to ensure that
no woman becomes pregnant and is exposed to
lenalidomide in the process.
So if you're a man taking the tablet,
you'll be asked to sign paperwork about, are
you going to use appropriate contraception?
Is your partner of childbearing potential?
So are they basically young enough to have
a baby?
Are you in a sexual relationship at all?
And the reason for that is to make
sure that the medication when it's in your
system doesn't get passed through to the woman
through intercourse basically.
And then if you're a woman, you'll be
asked similar questions about, if you are planning
a pregnancy, you need to tell us, we
need to take you off the medication and
you need to use appropriate contraception.
And then if you're not engaged with any
intimate relationships at all, or you just think
you're too old and it doesn't really matter,
you'll still be asked not to share the
tablets with anybody and any tablets you don't
take, bring back to your hospital just to
make sure these tablets don't go awry.
So that bit of paperwork is a bit
of a pain in the neck.
We must have done it between ourselves, Jan,
hundreds of times, but it is really important.
Honestly, it is a bit of tedious admin,
to be fair, but it does need to
be done.
I mentioned the blood clots earlier as well,
Sally, so people are on apixaban because lenalidomide
can increase the risk of blood clots.
And just one other thing as well is
it can cause cramps and cramps are not
uncommon on lenalidomide.
Do tell us, because actually tonic water is
very good at keeping hydrated.
Magnesium, some people find helpful as well.
So it does have a lot of side
effects, but it is generally better tolerated than
thalidomide.
That's why it is really good that we
now have access to this drug in this
setting, basically.
So to complete the quartet is steroids.
Now I could rill off a whole bunch
of side effects, but often steroids initially make
people feel better.
They're good at treating myeloma, improving the kidneys,
giving people more energy.
But if you notice you can't sleep, your
mood is affected, do tell your doctors because
this is not uncommon and the doses can
often be reduced quickly.
It can make your tummy a bit sore
as well, can often cause swelling as well
in the legs.
But certainly people who are having a transplant
are broadly under the age of 70.
And in this group, our patients, I have
to say, because of the way we give
the steroids in bursts, they do tend to
tolerate the steroids okay.
But if you don't, it is often the
first drug that we reduce.
And especially if we see those myeloma proteins
going down, you know, very quickly, and we're
comfortable about how things are going, it may
be that after, you know, eight weeks even,
or sometimes even beforehand, we can really start
to dial down the doses of steroids.
Yeah, definitely.
You know, we've done a whole podcast on
steroids because they are problematic.
So do have a listen to that podcast
previously if you're new to this because it
might be useful.
Thank you for listening to the Myeloma Minutes
podcast.
Proudly partnering with Myeloma UK.
For more credible myeloma-related material and support,
please visit the myeloma website at myeloma.org
.uk. That's myeloma.org.uk. Or call the
info line on 0800 980 3332, which you
can find in this episode's description.
That, as you said, is the quartet to
make their beautiful music together to control the
myeloma.
They do a good job a lot of
the time.
I suppose a lot of people are going
to be listening and saying, well, is it
going to work?
This is the key thing.
And the great thing is that, broadly speaking,
at least at the beginning, it works in
everybody.
Yeah, I agree.
And actually, for the majority, it will work,
you know, really well.
And ideally what we want after 16 weeks
is for the abnormal proteins to have gone
down by 90% if possible.
And that is our aim.
In some people, it will be more.
And it will be completely undetectable in the
blood after 16 weeks.
And in other people, it won't be so
good.
But, you know, what we see is that
people respond quickly.
And the vast majority of people, you know,
do really well.
Yeah, they do.
I mean, this combination, as you said, works
near enough everyone at the beginning.
And then it maintains that response in well
over 90% of people.
So the odds are, if you're going to
have this treatment, it will work for you.
And keep things nice and controlled.
Just one thing to say about the response
jam.
Again, this is a separate podcast.
Some people's power proteins come down really slowly.
If that's you or your family member, don't
worry about it.
Talk to your doctor about it.
It doesn't mean the treatment's not working.
It just means it takes a little bit
longer for the proteins perhaps to clear from
the circulation or for the myeloma to respond.
But as long as it's going down, that's
what we need.
After 16 weeks, you know, and probably sort
of within the last four weeks of your
treatment, people start talking to you about the
process of moving stem cells from your bone
marrow into the blood.
Because this combination is so good at treating
the myeloma, actually the process of taking stem
cells out does become more straightforward.
And with lots of people, it's with just
some simple injections called GCSF, which move these
cells into the blood.
And then you go on a machine and
cells are sort of essentially filtered out and
frozen.
Please do refer to the stem cell mobilization
pod for a full description of that.
And then after that, people will have their
stem cell transplant, which is normally around four
weeks after the stem cell collection.
But it could be anywhere between four and
10 weeks or even four and 12 weeks,
I think, depending on how busy your unit
is and various other bits and pieces, which
may determine the timing of your transplant.
Yeah, definitely.
So the stem cells are collected and then
you're given a date to come in.
And again, we've spoken about this at length
on previous podcasts.
If you're embarking on this journey, I would
recommend listening to this podcast.
I think the stem cell transplant itself can
be quite overwhelming.
To simplify it here, you come in.
A line is something called a PICC line
tends to be inserted into your arm and
strong chemotherapy is given and that's called melphalan.
That can cause side effects like low blood
counts and increase your risk of infection and
diarrhoea typically and soreness of the mouth.
And then following the melphalan, you have your
stem cells.
They're given back to you and they're just
given via that PICC line, that big sort
of cannula that's in your arm.
Now, the side effects of the melphalan, which
does cause all the problems, don't tend to
kick in immediately.
It can take some time.
Generally, the first week is pretty smooth.
The second week is where people can really
feel the effects.
But at the end of the second week,
the stem cells, which have been given a
week or so ago, tend to be working
their magic.
They're helping your bone marrow recover and you
start to feel better.
And at that point, when your blood tests
are looking more healthy, then you liaise with
the team on the ward and tend to
be discharged home.
So in hospital for the stem cell transplant
for about two to three weeks, it is,
I think, psychologically and physically, it's an awful
lot to go through.
But I would suggest take it day by
day.
The side effects of the clinical teams are,
you know, clinical teams are so familiar with
how to manage these transplants that, you know,
it's a very low risk procedure and we
know it just pushes the myeloma further and
deeper down and with better control.
You'll go home and hopefully recover fully.
Most people do recover their strength fully.
And around, you know, possibly a couple of
months after you've had your stem cells put
back in, you'll have more treatment.
And this is called consolidation.
And it's like a lot of people say,
well, hold on, why do I need this
again?
You know, I had this.
And, you know, there's a couple of reasons.
I mean, one of the important reasons is
that this has given us the best results.
And there's a kind of scientific reason as
well.
There's a thought that if you kind of
reset your immune system and your bone marrow
with a stem cell transplant, and actually using
chemotherapy on a reset immune system can be
effective, but in a slightly different way.
So it's almost like, you know, the substrate
is slightly different and that's why you may
get some extra benefit.
But, you know, thankfully it's not as long
and it's only another eight weeks.
And I have to say, certainly in this
setting, you know, I often, you know, don't
give steroids or give very little steroids and
will reduce the doses of other drugs if,
you know, people are still recovering or they've
picked up side effects.
So I certainly tend to be, you know,
relatively relaxed about giving slightly lower doses in
consolidation.
Sally, I don't know what you typically do.
I agree.
I think at that stage for the majority
of patients, they feel like the worst of
it, if that makes sense, is sort of
behind them in terms of they've been through
the shock of the diagnosis, getting used to
all those drugs that they've got to have
at those first sort of 16 weeks and
then the transplant.
So by the time you're coming out of
that and you're going into this sort of
eight-week consolidation block, you as a patient
and family members are very familiar with the
side effects of the treatment.
We know how well the treatments have worked.
Your doctor is very familiar with how you
fared through it.
And so actually modifying the treatment at that
stage is very, very common because we don't
want to give drugs that people don't need.
And we also want to make sure that
they're back on their feet, so to speak,
and feeling as healthy as possible.
So really normal for things to be tweaked
and adjusted and that doesn't appear to impact
on the outcome, importantly.
At that stage, we will be able to
see how good the remission is and can
do so with confidence.
And we're monitoring the levels of myeloma by
doing regular blood tests.
And, you know, around the end of consolidation,
I think, is when broadly people are thinking
about, you know, doing more detailed tests, Sally,
on how the myeloma is.
So what would you do at that stage
typically?
Yeah, I think the timing of this is
somewhat different.
So this, once you finish your consolidation, you're
about to start what we call maintenance.
And the beauty of this new regimen is
currently, or up until like last month, we
were just giving a tablet maintenance, lenalidomide.
And that maintains your remission from when you
started all this treatment till your disease came
back for about seven years, we think.
But now that maintenance, you're adding in, well
you're continuing with the daratumumab alongside it and
that looks like it really continues to deepen
your response.
So the myeloma stays beautifully under control.
But the way that we're now allowed to
prescribe these medications means that we have to
reassess how deep that response is to either
say you still need to carry on with
the daratumumab long-term or you can stop
it after a couple of years.
And the way that you do that reassessment
is you do a bone marrow test.
You do those really sensitive analysis to find
those cells.
And if your myeloma has been under control
and you can't detect it on two occasions
at least a year apart, then you can
stop the daratumumab.
So it's a bit confusing.
This takes a while to get your head
around.
So you have at least two years of
this daratumumab and lenalidomide maintenance.
And if you're to stop the daratumumab at
the end of those two years, you need
to have had this sort of undetectable disease
for at least a year.
So what that means for people is you
need to do a bone marrow test.
Now you can do it at the beginning
of starting the daratumumab and lenalidomide or you
could wait a year and do it later.
And you could do it like a year
in and then at the end of the
two years.
It doesn't really matter, although you might get
slightly different results at these different time points.
But somewhere along that pathway, you will need
a bone marrow to enable us to either
continue with the whole treatment or modify it
so that we can get the best response.
So, yeah, I think, Jan, maybe your practice
will be actually to do a bone marrow
when you enter into that sort of maintenance
phase.
I wonder if I might leave it a
bit, actually, just because you're more likely to
be in that lovely deep response if you
do it a bit later.
But really, sometime or other, a bone marrow
will be coming as you embark upon that
part of the pathway.
Yeah, we don't want to do unnecessary bone
marrows on people, for sure.
I do think that some people will want
to know before they start maintenance, whether they
have detectable myeloma or not.
But as you say, technically, you could just
wait a year.
And after they've had a year of maintenance,
and then the key thing is, as you
say, after two years of two drugs on
maintenance, if you've had a year where the
myeloma is just completely undetectable on this MRD
test, then you would drop down to lenalidomide.
And as things stand, that would continue until
the myeloma progresses.
But the way we're thinking about maintenance is
changing in real time.
There's a lot more talk about stopping maintenance
totally.
There is emerging evidence that in certain groups
of patients, you can certainly do that.
And I think we'll explore that maybe in
a future pod, and talk about maintenance in
much more detail.
We've already done a maintenance pod, but it
feels like we should actually do another one.
And Sal, for people who've got to 34
minutes in now, we've been chatting about this
approach.
How are you going to counsel them about
what this approach can do for their myeloma
long term?
People are going to say, am I going
to stay in remission for two years, five
years, ten years, longer?
I mean, these sound like good numbers to
me.
What are you going to say to people?
And what do we actually know?
What do we know and what are we
predicting?
Yeah, exactly.
Great questions, Sam.
I mean, I think before I attempt to
answer that complex question, I think what's different
about this regimen is not just switching the
thalidomide to lenalidomide, not just the consolidation piece,
which we were given before, but slightly differently.
But what we're doing is we're adapting that
maintenance to each individual, to how well they
respond.
And we know having the combination, particularly of
daratumumab throughout that pathway, really does improve how
long people are in remission for.
Ten years ago, when we didn't have lenalidomide
maintenance, and people had relatively old-fashioned drugs,
a bit of Velcade and myofascializomide that may
not, and then a stem cell transplant, a
good outcome for a transplant then, and by
a good outcome, I mean how long it
took for their myeloma to come back, was
in the region of two or three years.
Honestly, it was that short, which seems really,
really, really ridiculous now.
Whereas what this study, which is called the
PERSES study, with this four-drug combination before
and after the transplant and these two drugs
as maintenance, has shown or anticipated that, on
average, the remission period will be 17.1
years.
Totally different.
And that shows the power of using the
right drugs in the right people.
Now, this hasn't been proven, because we haven't
been monitoring people for that long, because the
study didn't recruit whenever it was at the
beginning of the century.
But nonetheless, that's what's anticipated, and those predicted
results have enabled NICE, our funding body, to
actually say, okay, we can support this regimen
because the outcomes are so good.
I mean, it's an estimation, we should say,
right?
Absolutely.
Because the length of follow-up is around
sort of eight years, right, at the moment.
What we know for sure, that after that
kind of seven to eight years, around 80
% of people are still in remission, which
is a huge number, right?
Like, you know, an unprecedented number, you know,
of a big number of patients from a
very well-run, you know, organized clinical trial.
So, I think genuinely, for the type of
person who would have fitted into the criteria
of the trial, and this is an important
thing to say, because we will treat people
on this who wouldn't have been illegible for
the trial for a number of reasons, and
their results may not be as good for
a number of different reasons that are not
related to myeloma.
And I think that's really important to say.
But if a patient clearly fitted the criteria
in terms of fitness and age and all
of those things, we can say to people
that comfortably over 50% of people will
still be in remission after 10 years.
Definitely, definitely.
Which is unbelievable, and that's the kind of
thing that, you know, when I started as
a consultant and I used to do lymphoma
and other things, there were, you know, some
diseases where actually you could control the disease
for that long.
Things like, I don't know, something like follicular
lymphoma.
But now to be saying that, we will
be saying that in clinic from next week,
Sally, right, is remarkable.
It really is remarkable.
And what's worth remembering here is this is,
you know, potentially being on treatment, you know,
the treatment continues and maintenance continues for all
those years and less new data comes through
telling us that we can stop it altogether.
So, watch this space.
But actually, that's the average.
So, there'll be 50% of people that
may be in remission for longer than that.
And if you have your transplant in your
mid-60s, for example, and you're in remission
for 20, 25 years, that may be the
only treatment you ever need.
So, if you were to look on the
plus side of this, the gains are enormous.
However, as we've spoken about before, Jan, not
everybody is so fortunate.
Some people will still relapse early.
But early in the context of this study
is different from early 10 years ago.
Early 10 years ago would have been three,
four months post after the transplant.
Here, it may be three or four years,
for example.
And so, yes, that's still not as fabulous
as the average which is predicted in this
study.
But in three or four years' time, the
field of myeloma will once again be very,
very different indeed.
So, I do think even for those people
who don't get these ridiculous responses, if I
can say that, please, you know, don't lose
hope as you move forward because the field
is moving so fast that the new combinations
coming through at relapse can also offer considerable
promise.
So, I'm really optimistic about this treatment.
I think we're very familiar with the drugs.
We're very familiar with the pathway.
It's just great that this is available for
our patients and may result in these incredible
outcomes.
We know, you know, talking about a group
that we know don't do as well are
people with high-risk myeloma who have these
genetic features which means that, yes, they respond,
but getting them to an undetectably low level
and keeping them there is very difficult.
And for the high-risk patients that were
in the trial, and there's always less high
-risk patients in trials than the ones we
see in real life because of the nature
of their myeloma sometimes, but for the ones
that got into a trial, you know, the
numbers are lower, but still around 50%
of people are in remission at, you know,
around seven years, which, you know, is still
a very big number for those high-risk
patients that were in the trial.
So, it is, you know, it is a
good treatment for this group of patients as
well.
Certainly not perfect, and there are a number
of things that could be tweaked and changed.
It is a treatment that we will be
giving to the majority, you know, the vast
majority of our patients who are going to
have a transplant.
What I would say, Sal, is that sometimes
people present with bad kidneys and their kidney's
not working well at all, and it's very
hard to give lenalidomide when people's kidneys don't
work because it is sort of excreted, you
know, partially through the kidneys.
In that setting, thalidomide is a very good
drug.
So, there will be a small number of
patients, in my practice anyway, that will still
get DBTD.
I don't know what your thoughts are on
that.
Yeah, interesting, isn't it?
I don't like thalidomide, to be frank with
you, Jam.
It's a dirty drug, using that word, but
I think it's, for me, I find it
very helpful in renal failure in that sort
of setting.
Well, I'm sort of quite keen to sort
of like, you know, chuck that one into
the bygone era and throw it out the
window.
So, actually, I think my approach, and everyone
will be different, is to go in with
a really low dose of lenalidomide and just
monitor the blood counts and see how well
it's tolerated.
There's no one-size-fits-all.
I think, you know, the incredible point that
you're making is actually we have options.
We can choose.
We have a gold standard regimen here, but
we can modify it.
And in the process of modifying it, we
may get equally good responses or responses which
are still very good indeed, particularly, you know,
relative to what we've experienced in the past.
So, there it is, the Perseus regimen.
Just as a finishing point, Sally, we always
talk about the new four-drug combination.
But, of course, for every new trial, there
are people that didn't get the four-drug
combination, right?
There are people that got the three-drug
combination on the trial.
In this study, it was VRD, so you
didn't get the daratumumab.
And any trial I look at, I always
like to see how people who, you know,
didn't get the treatment that looked as good
as, you know, the one that won, as
it were, how they did.
And the reason why this is really important
is that in this trial, you know, the
three-drug combination was VRD, so no daratumumab,
and then you got single lenalidomide maintenance, okay?
Now, all of these drugs are generic now.
And this combination of drugs is extremely cheap,
like genuinely in places that do not have
advanced economies and can't access the most modern
drugs for, you know, whatever reasons.
You know, VRD, a transplant, and lenalidomide maintenance,
we know with very long follow-up now
that, you know, around 55% of people
are still in remission at seven years.
And actually, you know, the median has been
reached.
So 50% of people are still in
remission after around seven years.
So that's also very good, and we shouldn't
forget that.
And it's also very affordable, and it means
that, you know, there is still a lot
of inequity around the world in myeloma treatment,
but that old treatment is actually very good
for certain groups of patients.
I think you make a really important point,
Gemma.
I mean, it's always very exciting, and we're
always tempted, aren't we, to lean into the
newer drug and these incredible improvements.
But not everybody needs all of these fancy
drugs.
You know, some people have myeloma where literally
anything that you give to them will work.
And so for those patients, it may be
particularly, as you say, if resources are limited,
that modifying this regimen can still offer very
good outcomes for some patients.
Or in fact, if you can't tolerate it
all, and you just have to take some
of the treatments away, whatever the situation might
be, I think the combinations are getting better,
the individual drugs are getting better, and all
in all, that's a win for all of
us.
Indeed it is.
If you're just about to embark on this
treatment approach, look, good luck.
Keep talking to your doctors, your specialist nurses.
Tell them how you're feeling.
You know, it really is a journey that
we take together with you.
We hope you have a good outcome.
Your myeloma is well controlled.
And thanks for listening.
Thanks, John.
This has been the Myeloma Minutes.
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