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.
Hello, Sally, how are you doing?
Yeah, I'm good, thank you, good to see
you again, Jam.
Yeah, no, so we've got a really cool
pod today, haven't we?
So we've got a leading light of UK
myeloma on and he's coming to talk to
us about, you know, the area that he's
really, you know, got interested in the last
few years.
You know, he's, you know, he's wise, he's
funny, he talks with such eloquence and real
insight about myeloma and I really hope that
everyone enjoys this conversation with Professor Gordon Cook.
Yeah, I agree.
I mean, we've already had the chat with
Gordon, don't we, so we know what's coming
for our listeners.
I think there's a lot in there to
unpack, you know, I think Gordon is such
an expert in his field, having worked in
this area for decades, and so he sort
of walked us through, didn't he, Jam?
All the trial work he's done, what that
means to people, frailty, which is such a,
I think, a challenging issue.
It's a really complex kind of idea to
get across and he explores that from so
many different angles.
So I found our conversation incredibly interesting and
really illuminating and every time I speak to
Gordon, I feel like I learn something new,
so watch out, listeners, there's a lot to
squeeze into this one.
Yeah, so when he talks about frailty, I
mean, I think it's a word that, you
know, is used just in normal life, people
being frail, but what do we mean by
it when we're talking about myeloma?
Gordon explains about the fact that we can
sometimes appear to be pigeonholing people.
We can label them as frail or not
frail, fit or unfit, and actually what that
might mean for somebody, how they might then
respond to that, whereas actually, I think what
we then discover as we continue our conversation
with him is that actually the concept of
frailty is about so much more than badges.
It's actually about trying to figure out how
to get the best out of a treatment
so that that person responds as best they
can to that treatment and gets fitter.
And he goes into some depth, actually, which
I found illuminating, interesting about the fact that
this is dynamic, meaning that, you know, your
fitness, as we know, changes depending on how
well we are, have you got a cold
or not?
What treatment have we just had?
Have we been on holiday?
Whatever it might be.
And so I think he speaks to the
fact that frailty is more than a badge.
It's about us living our human lives and
being as healthy as we can and how
that interacts with the diagnosis of myeloma.
Indeed.
And part of this is because two thirds
of our patients when diagnosed are over the
age of 70.
So we see lots of people who come
in and even if they didn't have myeloma,
they might walk slowly and may be a
bit hunched because they've had osteoporosis or they
picked up diabetes or high blood pressure and
maybe had a little heart attack or a
stroke.
So all these things, unfortunately, that build up
with time are there.
And then you put the myeloma on top
of it.
And what I think we're all trying to
do now is unpick all of that in
a much more scientific way.
So, you know, back in the day, you
know, Sally, when we were learning medicine, you
know, it was just like, you know, the
great experience of the clinician.
It's like, you know, they can look at
you and say, ah, immediately I get a
sense of what this person is like.
So on the basis of this, in my
experience, we should only give this dose of
a drug or, you know, and we talk
about it when we're talking with Gordon, right?
You know, the end of the bed test,
you know, just to get a sense of
how people are.
But Gordon talks about how we're trying to
move that field forward and make it much
more rigorous and sort of make it more,
you know, data driven.
It's about more than just a thumb in
the air.
This person looks a bit like X, Y
or Z who I saw last week.
So I will do this, that and the
other in the same way or differently.
I mean, I think we spoke about it.
It's making sure that the person and all
that that then means is integrated into the
conversation, into the decision making and therefore into
the outcome.
So there's a lot to digest, isn't there,
Jan?
You know, but what a fantastic conversation it
was.
And actually, you know, we've just come back
from this international meeting in Glasgow.
Timed perfectly because Gordon was chairing that meeting.
So it's fantastic that we put him on
the pod at around the same time to
talk about his particular area of interest.
And he even wore a kilt.
But, you know, sadly, we don't have any
visuals of that.
But yeah, no, it was great to see
him up representing UK Myeloma with all of
our other wonderful colleagues, including yourself, Sally, who
spoke so well at that meeting.
So I hope you really enjoy this chat
with our good friend, colleague and mentor, Professor
Gordon Cook.
Gordon, welcome.
Lovely to have you here.
Thanks for the invitation.
It's truly an honour to be here.
So we thought we would maybe just start
by perhaps talking about frailty.
Frailty means different things to different people.
But us as myeloma doctors, we have been
focusing on frailty really for the last 10
years since we created this myeloma frailty score.
And it's quite artificial in many senses.
And it has lots of limitations, which I
guess we can talk about in due course.
What it's allowed us to do is try
to categorise people into those who are fit
and don't need special considerations.
Those who are frail, who do need special
considerations.
And then those in the middle, which are
intermediate fit.
And as I said, it's an artificial situation,
because let's be honest, human biology is not
binary.
It is a whole spectrum.
And trying to simplify the heterogeneity of ageing
biology into three classes is a tad naive.
If you look at the frailty scores used
in medicine and in general practice, they use
a different type of model, but it categorise
people into four or five different slots.
And that seems a bit more realistic than
trying to put it into three.
But anyway, put it into three, we do.
So that's so interesting, Gordon, isn't it?
And of course, we've worked or I've worked
alongside you to some extent for a little
while in this.
But I think if I was to ask
anybody in the street about frailty, there might
be a perception that younger people aren't frail.
And it's a condition which is defined by
ageing.
And I think the way it's been tackled
in the field of myeloma is much more
complex than that.
And I guess a question to you is,
why is this interesting to you?
Why aren't we just relying on age to
use as a guide in terms of frailty?
What does this actually mean for our patients?
Well, it's interesting because earlier in my career,
I was very much an intensive haematologist.
I ran a donor transplant programme.
I gave acute leukaemia treatment and obviously intensive
myeloma treatment.
But as I've got older and a bit
more wary of my comorbidities, then it's kind
of switched my thinking into the accelerated ageing
process.
And you're right, it's a complicated biological process.
I mean, for example, if you didn't get
any disease in your life, you would assume
you would be immortal, you would live forever.
But there is very good biological mathematical modelling
that shows that even if you never got
a disease, you as an organism, a human
being, would just stop existing after 155 years
of age.
So there is an inherent biological clock in
the background, and that's accelerated when you develop
concomitant disease.
And it always makes me smile when I
see a patient in the myeloma clinic and
they've got diabetes.
That's a comorbidity.
But in the diabetic clinic, their myeloma is
a comorbidity.
So there are these interplays between how different
diseases in an individual play.
For example, you've got a number of different
diseases.
You might say of hypertension, diabetes, heart disease,
well, all the meds that you take for
these individual diseases can have crossover effects into
tolerating other treatments.
So that's the comorbidities, polypharmacy effect on how
you deal with your cancer treatment.
In this case, we're talking about myeloma.
But also we do know is that cancer
can have an effect on an individual.
And rather than being a comorbidity, it can
be a driver of accelerating aging.
And consequential to that, the fact that you've
got a disease like cancer on board is
making you as an organism perform less well.
Now, we see that when we treat the
cancer, then what happens is that the fitness
of that individual, and I use fitness in
inverted commas here, frail, non-frailness, if you
want to put it that way, gets better.
And that signifies the cancer overlay on the
functionality of the individual.
And frailty, therefore, shouldn't be sought as a
badge to pigeonhole patients.
It is actually dynamic.
It does change.
In myeloma, there's some work done that looked
at not the frailty when they were diagnosed,
but their frailty score at a year after
being treated.
And that had a more accurate reflection on
the outcomes for those individuals than what they
were scored at a diagnosis.
Again, highlighting this whole dynamic process going forward.
So, to come back to your question about
age, age is just a number.
We see this time and time again.
Thanks, Gordon.
For our patients coming in through the door,
I think something that a lot of doctors
struggle to work out, and you touched on
it in just what you were just saying,
is we know that myeloma is traditionally a
disease of the elderly, with two thirds of
our patients being over 70 when we meet
them for the first time.
It's really unpicking the frailty that comes with
other diseases they picked up versus what has
happened because of the bone disease, the kidney
dysfunction, the impact of the myeloma.
And families, as well as patients, thinking, are
you going to undertreat me or are you
going to potentially overtreat me?
Because I just can't quite work out what
level of treatment I'm going to be able
to tolerate.
So that is a very important part of
our clinical practice.
Just before I come to that, I would
like to touch on the issue that how
do we actually as clinicians categorise people as
frail?
We, Jam, Sally, we eyeball people, don't we?
We've been around long enough that we can
see somebody who is going to struggle with
treatment.
It doesn't mean they will struggle with the
treatment all the way through, but it means
that you may have to go slow to
get a foot in the door with the
myeloma and then you can build up.
And how do you kind of categorise that
clinician experience?
So a couple of years ago, I was
involved in a global project looking at real
world data.
It was called the Insight Project across Latin
America, North America, Europe and the Far East,
with the exception of Australia, because they had
their own project.
One of the many things we did was
that we got the research nurse and the
team to do the international myeloma frailty score,
blinded to the attitude of the clinician.
And the clinician was to eyeball the patient
and pick which score they were going to
get.
And the concordance there was between 70 and
80 per cent.
However, a lot of it was based on,
because we recorded the experience of the clinician,
whether they were a myeloma doctor in an
institution or whether they were in a community
hospital or district hospitals, as we call them
in the UK.
And that did make a difference.
So clinical experience is important, but it depends
on how much they have in the game.
So coming back full circle to what you
say, before the myeloma IMWG, International Myeloma Working
Group, frailty score came into being, we would
sit in clinic and in our minds, categorise
somebody as at risk of treatment intolerability versus
not at risk.
And that's really what the frailty score does.
Now, the frailty score was designed to be
a prognostic biomarker.
Now, what that means for your listeners who
are not familiar with these terminologies is a
prognostic biomarker is an entity that you measure,
whether it's in the lab, whether it's in
your wee, whether it's a scoring system.
And what it does is it tries to
predict your outcome as an individual.
Yes, we have a staging system, but this
is to try and elevate the staging system
to try and work through into some stratifying
patients.
But what a prognostic biomarker doesn't do is
tell you how you manage treatment.
That would be a predictive biomarker, and that's
a prognostic biomarker that has been proven to
be able to allow you to direct your
clinical treatment.
And as I said, we've had the myeloma
frailty score now for over a decade.
And there's lots of clinical trials and real
world evidence showing that it is a good
prognostic biomarker, but absolutely no evidence about it
being a predictive biomarker.
So this leads me unashamedly into talking about
myeloma 14, the fitness trial that Graeme Jackson,
a very good friend and colleague and my
mentor, although he hates me saying that, him
and I set this up and we closed
it to recruitment in 2004.
We started the trial between first and second
lockdown and Covid, by the way, which was
a tremendous effort with the trials team.
And one thing we never thought we'd get
off the ground.
Anyway, we are now sort of analysing that,
looking to see.
And in that trial, what we did is
we everybody had a frailty score done.
We randomised people into receiving treatment as per
the licensed drug doses, modifying the doses according
to toxicity.
That's the control arm.
And the experimental arm was to see if
we could upfront change the doses based on
somebody's frailty score.
And we are now just in the process
of sending that information off to the journals
to be published, hopefully.
But it wasn't the positive study that we
hoped.
And I think deep down, if I'm honest
with myself, this is probably academic naivety on
my part.
When we designed the frailty score adjusted dosings,
we probably weren't aggressive enough.
So the frail patients didn't get a big
enough dose reduction.
That's the first thing.
Second thing is, is that this was using
a regimen with lenalidomide.
And as you know, we lenalidomide dose modified
people who have got kidney disease irrespective of
their age and physical frailty.
Well, I hadn't really thought about that as
a key player because that then compounds because
40 percent of the people who were in
the trial and were frail had kidney disease.
So even in the standard dosing, they got
a dose reduction.
So it gets quite complicated.
And then the last thing on my self
-critical crusade really, is that the French study
IFM 2017-02 demonstrated the benefits of dropping
dexamethasone, which any of your listeners who are
actually patients themselves or carers will be jumping
up and down at this point because that,
you know, everybody hates dex.
That was actually released, those results released well
after we started our trial.
Now, if we had seen those results, it
was a smaller study.
But if we had seen that, we might
have actually been bolder and dropped the dex.
So these are the confusing factors in there.
We didn't see any difference in the frail
group, but we did see a difference in
the intermediate group.
Now, you could see that's because the frail
group are frail and they're not getting any
better.
Park it.
The intermediate group are in that group because
their myeloma is making them less fit.
So if you treat the myeloma, they get
more fit.
That's possible.
And we are looking into that.
But that's really where the myeloma is.
So while clinically we feel this is the
right thing to do, start slow and build
up.
There isn't the body of evidence because it's
quite a difficult thing to prove, as it
turns out.
I mean, I find that so interesting, Gordon.
And if you don't mind me sort of
celebrating your honesty for even someone as experienced
as you are with this, you know, wealth
of trial experience.
It just goes to show how that learning
is continuous and actually you build on the
research with each trial that's published and that
pushes in the field forward further.
But it is interesting, isn't it?
I remember when that data was, your data
from your study was presented in the States.
And nonetheless, it still caused huge ripples throughout
the audience and actually the international community, because
I think, challenge me if I'm wrong here,
but it did show how important doing these
assessments are.
And actually, I would say over the last
few years, frailty has really been at the
forefront of our minds in clinic, in trials,
in almost everything we do in a way
that it wasn't before.
And I would say that your study really
paved the way for that and changed how
we think about managing people living with myeloma.
I think you're right, because as I said
at the outset, that frailty or physical fitness
to tolerate cancer treatment, to be more accurate,
is much more complicated and complex issue than
a simple scoring system.
And that's not to criticise what Antonio Palumbo
did in 2015.
You're right.
Before that, we never really paid a great
deal of attention to it other than maybe
day to day clinical service delivery.
But now, of course, frailty is very much
on the map and coming full circle to
what was raised right at the very start
is that this AIDS thing, with myeloma, we
do have people who score as frail, who
are in their 50s and in their 40s.
And it's not an AIDS thing as such.
I think the IWG frailty score is quite
a blunt tool.
For example, it cohorts ages.
Now, what that means for your listeners is
that it doesn't look at age as an
individual number.
It looks at age in groupings.
So you are in your 70s, you're in
your 60s, you're in your 80s, da da
da.
And the problem with that is that you
could be a fit person who, by virtue
of your 80th birthday, you are categorised as
frail.
No, you're not.
You've just turned 80.
Now, we, David Cairns and myself, a colleague
in the trial unit in Leeds, we created
a different, I wouldn't say it's a frailty
score, it's more of a vulnerability score.
It did predict outcomes.
It did predict people having serious complications so
they didn't survive the early months.
And this is called the MRP or the
myeloma risk profile.
And in that, we use more objective measurements,
but also we used age as a continuous
variable.
So we kind of got rid of this
in a pigeonhole.
It's different.
I wouldn't say it's better, but I think
what it highlights is the need for us
to kind of start to look into this
with a bit more detail.
And then there's the role of biomarkers.
Do we look in your blood?
Do we look in your weed?
Do we look in your poo?
Do we look at the CT scans, MRI
scans, PET scans?
You had a diagnosis and repurpose them.
These are things that my research group are
looking at.
We take imaging.
We don't need to have another scan.
We can take the scan you've already had
and actually delineate how much fat there is
under your skin versus around your organs, how
much muscle you've got, how much fat's in
the muscle.
And we're currently using the trial data sets
to see if this is a way that
we can actually highlight more vulnerable people compared
to those who will tolerate treatment from the
word go.
One of the things, for example, we do
with this is we measure the calcification of
the aorta, which is, as you know, is
the main artery in the inside the abdominal
cavity.
And that can actually predict better than the
cardiovascular risk scores, people having cardiovascular risk events.
And we've proved that in our real world
data set of 100 patients.
We're now looking to examine that in the
Myeloma Fitness trial, which is over 700 patients.
So repurposing imaging may add to the frailty
score, the clinical frailty scores we have.
The blood and wee and poo side of
things, we're still very much at the start
of that journey.
So what we're looking at is the effects
of ageing on the immune system and how
that accelerates in people who are frail.
We are looking in the pools of the
bugs of what's called the microbiome.
So it's interesting.
It's a little bit different then, isn't it,
from your standard clinical trial of drug X
versus drug Y.
It's this is it sounds like it's much
more focused on the patients.
What is it we can learn about the
patient that then interacts with the treatment rather
than it just being the treatment by itself?
Is that fair to say?
Yeah, that's exactly.
In fact, everybody on the trial, this is
the Myeloma Fitness trial we're talking about, got
the same treatment, the same three drugs, and
therefore it was not about treatment A versus
treatment B.
It was about the delivery of it, trying
to tailor and make it to the patient.
But that's what comes back full circle, because
the frailty score pigeonholes people into three groups,
which is probably too blunt.
And we could probably do that better.
But you're right.
It's about trying to tailor make the treatment
towards the patient and talking about the patient.
It's interesting that the patient's perspective of frailty
is very different to ours.
It's quite a negative phrase.
We know what we mean by, you know,
in the medical sense, what we mean by
frailty.
We are talking about treatment tolerance.
We're talking about complications.
We're talking about adverse events or whatever.
Whereas a patient to be told they're frail,
it's kind of a slap in the face
really, isn't it?
And we'll run a workshop with an allied
health professional colleague of mine in Leeds with
some patients.
And we said, you know, we said to
them, who here thinks they're frail?
No hands went up.
We then explained what the myeloma frailty score
was and we had about 20 percent hands
go up.
We then actually measured their frailty by the
IMWG frailty score and they were all frail.
And then we said to them, right, OK,
this is very subjective.
Give us, you know, if you say frail,
what's the first word comes into your mouth?
And we built a word cloud around it.
And just looking at this word cloud, it's
full of negativity.
So I think we're conveying the wrong message
to patients by saying, oh, you've scored frail.
I think we need to be thinking about
different physiology.
Now, you know, being Scottish, language isn't my
first entity.
But, you know, cleverer people, me, will come
up with proper phrases that actually can describe
and be meaningful and not offend the patient
as we go, because this is a two
sided part of the journey and we need
to take the patients with us on it.
Well, it really makes me think you're actually
saying that.
And for our listeners, I wonder how many
have actually have gone into clinic and been
told, we have determined you are frail and
therefore we are going to treat you differently.
I strongly suspect very few patients have had
that experience, either because the doctors aren't thinking
about it in that sort of objective way
or they don't want to say that to
the patients because it's too risky to do
so, too worried about obsessing people.
And I guess if you agree with that
statement, Gordon, I wonder, do you talk to
patients about it in clinic?
And if you do, how do you explain
to them, I think or we think that
you're frail and that means X, Y or
Z?
Yeah, I think you're right, Sally, because there
are people, not all services measure people's frailty
using the frailty score.
The ones that do, I suspect, don't really
that categorisation.
They use it more as an internal way
to consider patients.
But I would like to think that they
will use it in their clinical practice to
modify how they deliver treatment.
How do I do it?
I try to describe rather than badge.
So rather than say to somebody, you're frail,
I'll explain to them what that means in
terms of what I'm going to do, how
I'm going to do it without using the
word frail.
And a lot of that's informed by us
having done that, you know, group session to
look at the, you know, what does a
patient think about getting a badge?
So I will use that to try and
explain why I'm going to do what I'm
going to do or suggest to do about
treatment, dose reductions, getting rid of dex after
the first couple of cycles, this kind of
idea.
And it's about, as you know, it's very
much about getting the patient on board so
that both of you can take that journey
to where it's going to give the best
results.
But yeah, it can be quite tricky.
Thank you, Gordon.
And I think something that we always think
about in Oxford as well is that the
makeup of the other services that we could
use and the expertise that is out there
in medicine that we don't always have access
to that can really help you define the
levels of comorbidities.
You mentioned polypharmacy.
People are on so many drugs.
We've tried to reach out to geriatricians or
elderly care experts, get more input from, you
know, physiotherapists and other really important allied health
professionals.
How do you see the wider MDT as
part of managing that frailty?
And I think a lot of our patients
find that they can't access all those services
in the way that I think could potentially
really dynamically change early frailty quickly and lead
to sort of improving outcomes.
Yeah.
So what I'd like to do, what I
am able to do as per usual in
the NHS is quite a difference.
I mean, what I'd like to have is
a one stop shop, multidisciplinary, you know, sort
of a motif of the patient really.
They're able to look at all aspects, not
just look at the myeloma, but look at
the comorbidities, the polypharmacy, look at the nutrition.
Dietetic input is hugely important in this population
of patients.
They are vulnerable.
They are losing muscle mass quicker than their
age compatriots because of the disease and the
treatment, particularly steroids.
And then there's the role of exercise.
And I'm not talking about, you know, 84
year olds down the gym in Lycra pumping
iron, but I'm talking about actually trying to
sustain the muscle mass they've got, limit, minimise
the loss and therefore having physiotherapy in there
for structured exercise programmes alongside dietetics to have
structured diet programmes that are going to load
protein in particular, I think would be immensely
helpful in that space.
That's the ideal.
The reality is, you know, our physiotherapy colleagues
are pushed, they're understaffed, our dietetic colleagues are
understaffed.
So trying to get input is a bit
piecemeal, but ideally that would be what I
would want to do and basically try and
get a bit more accurate, tailor made assessment
of the individual in front of me and
what they're capable about and how we can
improve that going forward.
I'm a great believer in exercise and what
it can do for, you know, for patients
undergoing serious treatment.
I know you're looking at me, Jan, thinking
you don't believe in exercise looking like that,
but trust me, I do.
But it's particularly important for patients going through
cancer treatments.
In hematology, blood cancers, we don't often have
the windows to intervene that people do with
solid cancers.
So you diagnose your colon cancer and you're
going to have your surgery.
There is a gap in the diagnosis to
the surgery.
You can pre-hab, get your surgery and
then you can rehabilitate.
We don't really have that luxury in blood
cancers.
We made the diagnosis.
We've got to crack on with it.
Therefore, rehab is probably going to be more
important for blood cancer patients than the pre
-hab, with the exception perhaps of autograft patients
where you've got a window there you can
boost them.
But it definitely makes a difference.
We've got the NHR Macmillan Cancer National exercise
guidelines just coming out.
It was a labour of love.
It's taken about a year from inception of
this to actually having the paper written.
And it's just been the finishing touches are
being added to it.
And that will give a framework so that,
you know, individual regions or, you know, sort
of services can look at this and say,
right, there's the evidence, there's what they're recommending.
What can I do to try and bring
some of this into practice?
And that is especially true for diseases where
blood cancer disease, where it's in the older
person like myeloma.
Again, it's about tailor making it because it's
what you start from as a level of
exercise to where you think you want to
go with it.
You know, some people are higher start.
Well, their goals might be different than somebody
who is less good, but definitely a huge
fan of that.
And I think it can improve both your
living with myeloma, but also your survivorship going
forward.
And it sets you up because myeloma is
still a relapse remitting disease.
And the exercise will set you up to
tolerate the next round of treatment and the
round of treatment after that better than if
you don't do it.
Thank you for listening to the Myeloma Minutes
podcast.
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info line on 0800 980 3332, which you
can find in this episode's description.
I very much share your vision, your idea
of what I would describe as a utopia,
your one stop shop.
But I guess what's also going through my
mind is people living with myeloma come from
all walks of life, and that includes the
very richest and the wealthiest and the most
educated in society and the other end of
the spectrum.
And we know there can be that link
between diet and, for example, your social deprivation
or your ability to exercise.
And I think some of your work has
explored that link between, for example, how healthy
you may be or how frail you might
be and your background.
I don't know if you can explore that
with us and what that link might look
like.
Yeah, so we are looking at real world
data from across England that's included everybody who
is in the National Cancer Registry, and we've
got about 45,000 myeloma patients in this.
And that big number allows us to start
delving into what does your postcode mean for
you in terms of your outcomes and both
in terms of social deprivation, but also there
are differences between coastal, rural and urban, and
it's not just as simple as deprivation.
And a lot of it can be down
to your access to treatment.
You know, here in Yorkshire, if you're coastal,
then, you know, you're going to be probably
two hours to my centre and then two
hours home again.
That's a lot of effort compared to somebody
who lives in Leeds, who actually Leeds transport's
not great, so it still could be two
hours on the bus.
But theoretically, it could be 20 minutes and
we're just starting to get a bit of
an understanding of how that affects treatment, treatment
delivery and more importantly, outcomes.
And to come back to the workshop that
we did with the patients, one of the
things that we're now going to do, and
that's the advanced nurse practitioner, Jenna Tate, she
did this work.
She's now moving that project on to start
to look at the underserved populations.
So actually taking these questions about frailty and
treatment tolerance and how we can affect dietetic
advice as well as exercise advice to those
underserved populations.
And we're going to do it in a
slightly different way.
We're basically going to convene community faith leaders,
put the problem to them to see if
they can advise us how best we can
then take the next step, taking it into
the community as such, because we're going to
learn from the people who know if we're
going to reach out properly, because notoriously, patients
from underserved populations do not take part in
clinical trials or clinical research for a whole
variety of reasons, suspicion being one of the
main reasons.
And if we're going to break those barriers
down and rebuild that confidence.
So we're going to start by doing that
fairly soon so that we can try and
see, depending on your community background, there could
be a number of quite significant challenges that
are different to that white middle class or
white upper class or even white working class.
And as again, we've said it time and
time again, haven't we?
One size doesn't fit all.
So we need to try and work out
what's going to be the best thing for
the population that you serve.
Yorkshire is a multicultural population that I think
probably does reflect what the UK sees.
But the reason I mention that is because
a lot of evidence that comes from the
US isn't transferable because, for example, the imaging
that was done looking at the body composition
that I mentioned earlier, there's some of that
work being done in Wisconsin and it looks
good, but it's in white middle class people.
That's not transferable to what we see in
our clinics day in, day out.
So this is why we've got to go
back and ask the question, OK, I found
this out, but what does it mean for
the people of West Yorkshire compared to the
people of North Yorkshire?
Those are two very different counties.
So you're right that we do need to
build up our understanding in modern day Britain
is very multicultural with different pockets and different
problems in those pockets.
It's so interesting.
There's so many layers to this, aren't there?
And it's really intriguing to hear the researchers,
someone such as you, delving into this at
such a what we would call granular, which
kind of means like a really kind of
like a really intense level to gather this
information.
I mean, there's a lot of a lot
of evidence out there, isn't there, relating to
the fact that, for example, a lot of
medicine is adapted to the male body and
the white male body.
And I guess you're speaking to that in
a far greater depth, which is really heartening
for our patients to understand.
You mentioned granularity, that big data set of
45,000 patients, I don't have a huge
amount of granularity, but the size of it
gives me breadth.
But there's another real world registry based in
York and I work with the colleagues there.
It's called HMRN.
And there we've got about four and a
half, five thousand patients where we do have
that granularity.
So using both data sets, we can get
breadth and granularity.
At the same time, and then ask those
questions.
So I just wanted to remind your listeners
about that.
Amazing.
So it's all looking good.
If you live in Yorkshire, I want to
move to Yorkshire.
Jam, let's go to Yorkshire.
I mean, they're not having an Ashes Test
match at Headingley, which I think is absolutely
appalling.
And I'm talking about that more on my
cricket podcast.
You've poked a bear about cricket.
I'm Scottish and I just do not get
cricket.
Anything, any sport where you don't break sweat
is basically sunbathing with utensils.
But anyway, moving on.
You've been playing it the wrong way, Gordon,
I think to be honest.
But we can explore that maybe offline.
It's really been interesting, actually, mainly listening to
you both about frailty, because you're both really
recognised experts in the area.
And actually, I was thinking it's a really
pertinent time to talk about it.
We've just had the second four drug combination
approved for our older patients.
And I don't know what you both think,
but we're seeing in real time the pros
of this.
But, you know, there have been some cons
as well.
And I think it's getting harder for people
to understand how to treat our older patients
now.
We have so much choice.
But with that comes great responsibility.
Sounds like a movie, doesn't it?
But it is difficult.
And I think some people are being over
-treated, some people are being under-treated.
You know, we've seen some bad toxicities.
I mean, practically speaking, Gordon, you know, as
a patient or a carer going into clinic
and, you know, combinations of things are being
discussed with them, how should the family or
the patient approach their doctor about their fitness
level, their frailty, their other diseases into really
making sure that whatever combination they give, it's
right for them?
Because, you know, it can be really difficult
now.
Yeah, it's an interesting question.
And I think I would probably say to
patients and carers who are listening that maybe
the question you want to ask the doctor
is, do you think I'm fit enough to
deal with this treatment?
Not saying the treatment is not going to
work, it's just saying, well, you're looking at
me.
Do you think I'm fit enough to have
this treatment?
The answer is yes, I'll take that advice.
Because as a patient, you don't know, at
least as a new patient.
When you come to your second line, third
line, whatever, you as a patient are getting
wise to, you know, the way we speak
and offer things.
But as a new patient, there's lots of
things swirling around in your head, lots of
emotionality about the diagnosis.
You've got to take in a lot of
facts for a disease you've probably never heard
of and thought at one point probably was
a skin cancer.
You've got to say, well, I think what
I would ask the doctor is, do you
think I'm fit enough?
You mentioned quads and triplets.
And, you know, we as doctors are a
bit prone for grasping the new shiny toy,
aren't we?
And oh, we can give quads and let's
give quads to everybody.
Oh, back off, because that doesn't fit everybody.
And I've, I took part in the trials
where we use quads and, you know, I've
broken people, you know, I've given them toxicities.
We know the main reason behind this and
it's the VRD is uplifted by companies into
their studies is the swab VRD.
And you've got to be Iron Man to
survive swab VRD.
It's not how we give it in real
world, but that's how we gave it in
clinical trials.
And we broke a lot of people with
it.
We still are going to be mindful that
giving four drugs, even with a real world
way of delivering the VRD element, we're still
going to be careful that we don't break
people.
And I always tell patients, this isn't a
sprint, it's a marathon.
And if I nobble you in the first
hundred meters, you ain't making that marathon, are
you?
So got to pace it for people.
And as you both said already, some people
are able to sprint a marathon, whereas other
people just need to go at their own
pace.
And we are learning through what we do
to be able to allow people to go
at their own pace because we want everybody
to finish the marathon.
So Gordon, may I have permission, please, to
use that analogy in clinic going forward from
now, I think that's a brilliant way of
describing what we're trying to achieve in the
field of frailty, the marathon.
I'm definitely a marathon runner, not a sprinter.
And it sums it up, doesn't it?
So, yeah, thank you for that.
I was going to ask you a great
question, isn't it?
And I think even people don't ask that,
just such a simple question.
Do you think I'm fit enough for this?
I think that can give you so much
information because also they will have to, as
we should as clinicians, we're being appropriately challenged
in a very nice way.
And then you give an answer to why
you are.
And as you alluded to already, Gordon, we
know that four drugs can often become three
now after a couple of cycles, because even
with the quads, we're aggressively stopping dexamethasone early
in quite a few of those patients.
And after six months, often you're just back
on to two drugs.
But as you say, it's a marathon.
And, you know, when they're feeling awful from
myeloma, sometimes giving four drugs attentively at the
beginning isn't what is needed.
But you hope that people have the understanding
of the situation to try and tailor it
as best we can.
The reason why I'm laughing is because, and
I certainly hope none of my colleagues will
listen to this episode.
I'm sure they've got better things to do
than to listen to me again.
They do giggle at quite a lot of
my analogies.
I talk about myeloma as being a boxing
match and how the patient's in the ring
with myeloma and we're on the corner.
And you can't kill your opponent.
But what you can do is knock them
on the canvas for as long as it
takes to give a big gap between round
one and round two.
And it kind of speaks to the notion
that it is successive rounds of treatment.
And also it allows me at the start
to introduce the concept that every round of
the boxing match doesn't last the same.
And the opponent gets wise to you and
the rounds get shorter.
And ultimately, for a lot of patients, the
bulk of your opponent wins out.
So, yeah, my colleagues, particularly my nurse specialist
colleagues, giggle when I start to go into
one of my analogies.
But to come back to the toxicities, so
I've been there as an individual, sat in
the chair, being faced with a doctor telling
you you've got cancer and this is how
we're going to treat it.
And I don't think I'm not the brightest
person on the planet, but I don't think
I'm that stupid.
But I struggle to think of questions that
were appropriate because your head's just once somebody
tells you you've got cancer, everything else is
background noise.
You can't focus on anything else.
And that's why, again, I would recommend to
any of your listeners who are patients or
carers that don't go to the appointments on
your own.
Go with somebody, family members, friends.
Two pairs of ears are always better than
one, particularly since that person with you, and
in my case, my wife, can be a
bit more subjective, a bit more objective.
And, you know, you as an individual, as
you sit there and you're being totally subjective
and you're blinkered and you can't spot the
facts that you need to spot.
And therefore asking somebody about how well does,
how well am I going to get on
with this treatment?
I didn't ask that.
And I didn't ask what the side effects
were.
They gave it to me and I learned
the hard way.
So, yeah, it is difficult to put that
onus on patients.
The onus should be on us as doctors
to be mindful of that and try and
work it into the conversations in a way
that can bring people on board.
And a lot of the time that's just
repetition.
I know I said this to you last
week, but I'm going to say it again
because I guarantee you, you only picked up
40% of what I said last week.
So, Gordon, for our last couple of questions,
two things to pose to you, which were
as follows, but I think you've already answered
them, actually.
But the first was, if you had one
message for patients or carers who are anxious
about the frail label, what would that message
be?
And similarly, for clinicians working within this field
and looking after myeloma patients, what would you
say is the one thing that we as
doctors need to understand about frailty and how
we manage our patients?
So from a patient point of view, what
you want to know is, is are they
telling you you're frail at this moment in
time and it's not going to get better
or is it something that's going to be
a transient thing?
Remember, frailty is dynamic because as you present
with your disease, you've got all your myeloma
and the effects it's having making you knee
make, kidney problems, whatever, alongside all your other
illnesses.
And therefore, we can't, nobody can determine at
the first time we meet you whether you're
actually going to be frail all the way
through your journey.
And the second thing is, is that going
slow and growing the treatment to see how
you tolerate it makes all the difference.
I tried to prove that with myeloma 14
trial and for the complexities we mentioned earlier,
it was a hard ask, but we as
clinicians inherently believe that that's the right thing
to do.
If we start to chip away at the
myeloma, we'll make you physically fitter, inverted commas,
and therefore I can up the treatment and
up the treatment.
And it comes back to that it isn't
a sprint, it's a marathon.
So yes, we all want to get the
myeloma into as low as possible, into MRD
or whatever.
But at the end of the day, it
is about that longevity and we want to
get the treatment in and build it up
so you tolerate it.
Amazing.
Lots for us to think about, lots for
us to take away.
Jam, I don't know if you've got any
other questions.
I feel like we've quizzed Gordon from left,
right, back to front every which way, apart
from cricket questions.
It's been great.
What will I say?
I can see two very nice guitars in
the background, so you just have to finish
the pod with just a little guitar solo,
Gordon, and then we're done.
I think the last thing your listeners want
to do is hear me batter away on
the guitars.
It will be better than our normal outro
music, but I won't put you on the
spot.
Maybe just a final question.
I mean, in 10 years time, Gordon, we
may all still be working.
I suspect I will still be working.
Do you think we will have a model,
some kind of a way of, you know,
we've talked a lot about personalising treatment on
this pod and actually understanding frailty and dose
adjusting in a logical way driven by data
is part of that sort of personalisation journey.
Do you think there will be, you know,
advanced models that we put in biological information
that then give us the information that allows
us to tailor treatment in a frailty?
Yeah, I definitely think that's going to be
the way forward.
We're going to take some blood based tests.
We're going to take some imaging tests.
We're going to take other features for the
patient's background, history, polypharmacy, shove it into a
black box that's got AI written on the
side and it will spit out what will
be the recipe to get that individual patient
to where you want to get them in
the treatment journey.
No doubt about it.
We're not there yet, but we're rapidly approaching
that.
And also, which we haven't touched on, I
mentioned a lot a bit about dietetics, dietary
advice and exercise.
But the other area that is growing is
an area called senolytics, and this is trying
to overcome the biological sequence of ageing.
Basically, senescent cells are cells that have switched
off their natural replication machinery and are just
sitting there.
And it's supposed to be a mechanism that
protects you to getting cancer, ironically.
However, as we get older, we accumulate these
cells in our tissues and they are not
just sitting there doing nothing.
They are actually sitting there making chemicals that
cause inflammation, a chronic sterile inflammation.
And that's what drives the age related diseases,
cardiovascular disease, metabolic disease, infections, et cetera, et
cetera.
And there's a wealth of research coming through
at the moment of looking at a lot
of drugs that are already licensed that can
have an effect on that accumulation of senescent
cells.
And that's what's called senolytics.
And of course, we're into the age of
immunotherapy for senolytics.
Believe it or not, you can get a
CAR T cell that will seek out and
destroy these senescent cells and improve the well
-being in mice, but it will improve the
well-being of aging mice.
So I think that you will see going
through the next five to 10 years that
side of medicine coming in.
It's kind of where the kind of tissue
healing medicine was five, 10 years ago.
And I think that will be a nice
partner to the anti-cancer therapy you give.
And therefore, we'll be able to make patients
tolerate better because we will improve their fitness.
We ain't going to make people live forever,
but we are going to make people live
longer, I think, coming forward.
What a fascinating place to finish.
And it sounds like a topic of another
couple of podcasts in the future.
Gordon, on behalf of both of us, thank
you so much for your time today.
Thank you for sharing your expertise, passion and
honesty for myeloma.
We're so excited to be coming to see
you, I think, introduce the International Myeloma Society
meeting in a couple of weeks time.
It's a proud moment for UK myeloma.
Thank you so much.
And please come back on next year.
And let's let's talk a bit more about
senolytics.
Yeah.
Thanks, Gordon.
And if any volunteers, if you run that
study with the sort of, you know, the
staying young forever Co-RT study I'm in.
So just remember that.
I want it twice.
Thanks so much, Gordon.
You know, always a pleasure.
Thank you.
See you soon.
So, Gordon, that was a bit of a
roller coaster, wasn't it?
I think just listening to that podcast again,
what I've realised, I think that one of
the key messages is that what frailty really
means is that not one size fits all
and that things change with time.
People get better.
People get worse.
People get stronger.
They get weaker and managing that, understanding that
and to some extent trying to prevent problems
from happening and predicting when they might is
really important.
And that's the essence, really, of the frailty
concept in myeloma and trying to live well
with myeloma.
Totally agree, Sally.
And I think understanding frailty is about trying
to optimise quality of life as well, because
there is that fine line.
We absolutely have to control the myeloma, but
in a way frailty is trying to help
us work out what is the minimum amount
of effective drugs that I want to use?
Because you don't want to overshoot.
You definitely don't want to undershoot.
And so much of still what we do
day to day in clinics, Sally, is a
guesstimation.
And I think that's being very honest.
A lot of what we do is educated
guesswork.
And hopefully, as we understand frailty better in
the future, we can measure things that might
say, well, actually, on the basis of this
information, I'm going to do this.
Yeah, totally with you there.
And what I would also say, as we
spoke about, actually, Jam, in our first podcast,
I think the idea of functional cure, which,
goodness, we discussed that a lot over the
last week.
But actually, if the era of functional cure
is here, it's on us, all of us.
That's the clinicians, that's the health care professionals,
everyone in a hospital, everyone in the community,
patients and our relatives, to make sure people
stay well and be as fit as they
can possibly be.
And that's really, again, what this is all
about is kind of tilting away from the
fact that I just need treatment to control
the myeloma to I just need treatment to
be as healthy as I can possibly be.
And that includes the frailty piece.
Totally, Sally.
It was a great discussion.
Thanks again to Gordon.
Yeah, and just to say, Jam, I challenge
you to live to 155 and I'll leave
that with our listeners.
Yeah, I mean, some people think I already
look about 130.
So I haven't got long to go.
Absolutely.
Thanks, Al.
Good, I'll catch you soon.
See you soon.
Bye.
Bye.
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