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Going to be having a chat about some of the issues that actually
affect our patients facing CLL. I'm Leslie Fallowfield.
I'm a professor of Psycho oncology at Brighton and Sussex
Medical School and. Yes, you might know me because
I'm a spender. I'm I'm a hematologist from
Munich. I'm happy to talk today with
Leslie about the subject. I'm usually not trained in, but
I think seeing patients, I think we, we, we can exchange some
experiences. OK.
So I guess what I'd like to start by asking you, Clemens, is
some of the advances that have been made in treatment terms.
So this changing landscape, I mean, what difference has that
made to you when you're seeing patients compared to when you
were a baby doctor? Yes, right.
So starting in the sidel field in the, I would say late 90s, I
think we were happy that we had a drug like fluid Arab being
available. So the perineal locks came into
the field and we are not even talking about chemotherapy at
all. And so it's still questionable
whether bendamustine a drug, for example, Kirsten Fischer and and
myself like very much 15 years ago, it's questionable whether
this drug is not using any damage at all.
We've heard yesterday from a young guy from Barcelona that
even we cannot use more than one of mutations using benamastin.
And from the patient's side, I think it's important.
Now when patients think we would treat their leukemia, they might
have pictures in mind, you know, that this means staying on the
warts, losing hairs and having a lot of MSS and nausea.
And I think this is the first misunderstanding we have really
to cope with. Great.
So, I mean, I think it's fair to say that the sorts of things
that might excite a clinical scientist can be less exciting
to a patient initially experiencing this very
frightening sort of diagnosis, especially because as we know,
some of these patients might be fairly asymptomatic and it could
even be diagnosed via a random blood test.
So I wonder if I could talk to you a little bit about
nomenclature, the words that we use.
But one can only make a choice about things if you understand
what the whose choices are. So I mean, it's pretty
difficult, isn't it, for an anxious patient who's suddenly
being told they've got a potentially life threatening
disease to cope with these esoteric concepts and words.
I can't pronounce things, let alone the names of the drugs.
How do you cope with that? Yeah.
I mean, it's getting very difficult even to remember all
the names, to pronounce them correctly, especially to think
about the patient having never had any contact with these kind
of drugs. So we have to take some extra
time. We have to write things on a
sheet. I usually also use my laptop and
show the names so they have the chance to read the names at
least. But I think even before talking
about a specific therapy, we tell patients they're for
leukemia and it's an early stage and we sent them home.
So the patient's leaving a door knowing he has a leukemia.
And this is also, you know, a kind of excited, you think
situation for the patient having sort of democlass swinging above
her or him. And this has to be reflected
also by the physician. You know that this is, we are
happy telling them it's early stage for us.
It's good news, but can still be bad news for the other side of
the patient and. I think that's a really
interesting issue, isn't it? Because if we think about all
the public awareness campaigns that have gone on, I think the
message for most of Western Europe at least has got through
that if you find a symptom, go and report it early.
And if you get early diagnosis, treatment will be initiated and
you've got a prospect of cure. So this goes counter to
everything people have heard. Hey, you've got leukemia.
But guess what? We don't need to treat it yet.
I. Mean it's it it.
It seems counterintuitive and I wonder if there's ever a
situation where a patient is so panicked by the fact that they
have got this life threatening disease that some people might
be tempted to treat a bit too early.
Right. I mean, there are this this kind
of temptation, isn't it, You know, the action mode I call it,
you know, just doing something. Although we know also big tries
CL12 try by Peter Langabins, for example, showing definitely
there is no use even in high risk early CLL to treat.
But it's also for a physician sometimes could be
unsatisfactory to send out a patient without doing anything.
This has to be learned. And so we have to take these
kind of mental health issues very seriously.
It should be said that in CLL there is not only a medical need
for this kind of mental health issues.
I think there's also a scientific gap.
We know it from breast cancer, from prostate cancer.
A recent trial in bladder cancer, for example, shows
exactly we have in 31 percent of patients mental health issues,
depression, anxiety, you know, fear to lose any, you know, also
welfare issues, things like this.
But there is no good signs in CLL so far.
And this can impact also on the treatment outcome.
There are data from other tries that it's not only the notation
status, it's not only TP 53. These simple issues like
depressive patients not taking a pill and we are using mostly
pills, Benito CLEX, PTK inhibitors can negatively impact
also on the outcome. So I think that's very important
to, yes. Stress, maybe we can come back
and talk about how well we do measure mental health issues in
our patients in a bit, but I want to come back to this sort
of like seemingly difficult concept for a patient to embrace
race that yes, you've got life threatening disease, but the
good news is we don't have to treat it.
So what does that patient actually do?
I'm sure all of you know the phrase of, you know, sort of
it's not watch and wait, it's watch and worry.
But I think we actually don't look at the personality
characteristics of patients sufficiently to recognize how we
have to potentially change the wording a bit.
Because for some patients, when you tell them those sorts of
things, they'll probably actually go away feeling
perfectly happy about it. They're able to almost sort of
ignore it, but I wonder how many fall into that category rather
than becoming vigilant about every ache, pain, sore throat,
lump or whatever. And worst of all, those patients
who have an anxious predisposition anyway, a trait
of being rather anxious, how many of those become hyper
vigilant, constantly going to their primary care physician,
reporting things? So I mean, how do we deal with
that, first of all? I think there is a significant
fraction, you know, just palpating lumps and bumps all
the time. And we all know these extra
sheets the patients are presenting to us with leukocyte
counts and we are a little bit annoyed sometimes.
But this seems to be just, you know, this is done by some
patients that want to gain by doing this again, some
self-control because they're losing control when we tell them
something about a still early stage leukemia.
But this is out of control. And I accept this for my
patients because I know maybe this helps them to regain
self-control. Although I'm as a physician,
maybe sometimes a little bit annoyed, you know, because
though it's useless whether you have 23,000 or 25,000 leukocytes
2 weeks later. So, So what about now sort of
coming on to, let's assume that the patient is going to receive
some treatment, but that could be continuous or intermittent.
Again, you've got a bit of a problem here depending on.
I would suggest not just the characteristics of the disease,
but the characteristics of the patient in how they can accept
that. Yeah.
I mean, we, we, we usually say a time limit therapy is an extra
bonus point for the therapy. I mean, we all know that we have
to to base a treatment decision on, you know, usually molecule
features, IG3 stairs, TP3 stairs, things like this.
In the end we make a choice, but there are patients that are very
happy with time limit therapy knowing this will come to an end
after 12-15 months, something like this.
But also patients being on Vanobi for example, they are a
little bit, there are some patients being horrified when
you know the treatment comes to an end, whether they are safe
enough. When we stop, then sometimes
very peculiar things start that patients are asking for MID
assessment. We again just heard this is
usually not routine practice, but still they want to know
exactly about their disease status MID assessment is asked
for. And so this we try to convince
them this is maybe not the routine practice and this is
maybe useless within clinical trials.
We do it, but all sort of clinical tries.
It's it's it's all done. On the other hand, we know there
are there are treatments, continuous treatments as you
just mentioned. This is when I tell the patients
you do take this pill lifelong. Lifelong always sounds
frightening. I usually then say OK, an anti
hypertensive drug you're also taking lifelong but you would
not think about stopping a hypertensive pill.
So try to make this kind of pictures or similarities in
medicine so that patients accept this kind of treatment.
Also, continuous treatment can be it's a safety pill.
Let's put it this way, every day you know they are taking.
This can also be can also gain or the patient can gain
reassurance by taking a pill every day.
Now that's an interesting sort of point really, isn't it?
Because obviously anxiety that this disease might sort of kill
me anytime soon is a psycho noxious experience for anyone.
But there are better ways to treat anxiety than to put people
on expensive drugs with potential side effects, aren't
there? And I just wonder how many
people have within their centers good well integrated
psychological support services that patients ought to
automatically be referred to, I would suggest.
I think there is still a major lack.
Also Germany that we routinely don't refer patients to
psychology specialists. There are some patient advocate
groups we and support groups. We just give addresses and we
just send them there. But we have for psychology
support, we have long waiting lists.
Also I think this is still an unmet medical need.
You know that we have to take these kind of disorders being
induced by by the leukemia diagnosis, that this has to be
covered also in a way by by good psychology support in the
system. I mean, it's quite interesting
really, isn't it, that I think some patients feel, you know,
but I'm not mad. And I, I, that's why I think it
should be integrated that this is an important part of care,
because we are always dealing with uncertainty in this issue.
And I think the general public actually do believe medicine to
be much more of an exact science than it actually is.
As we all know, facts are only sort of hypothesis that are
either refined or supported by the latest research data.
And trying to cope and deal with that, I think is pushy,
difficult. And I'm going to tease you with
another sort of thing about uncertainty.
And that is there are quite a lot of data now coming in
different areas showing that the tolerance of uncertainty of the
clinician who is talking to the patient will also affect what
the treatment decision is. Because if you as a doctor are
highly intolerant of uncertainty, you're more likely
to. But early on, I think provide
more aggressive therapy, order up more tests.
That's correct. I think we learned an expression
during the COVID pandemic. This is resilience, right?
And I think that this is also important on the physician side
to gain resilience and this this can be trained and to, you know,
just keep cool and bring the message to the patient, but not
just getting nervous about the leukemia per SE and starting
irrational treatments too early or things like this.
So. Do you ever feel blamed by the
patient if in fact you've reassured them and then the
disease does? Yeah, I mean, also you have to
be also resilient on this, you know, because as a physician,
you might get blamed to be inactive and doing nothing.
But it's a matter of convincing. I usually try to convince them,
you know, there is no need because we know exactly you will
not benefit when we start too early, we might even harm you.
But this depends then also on the patient's side, you know,
whether the patient is accepting this kind of scientific
knowledge from the physician. So communication is really very
important, isn't it? And I guess there's also a
social legal moral imperative now to be more patient centered,
to involve patients more in their decision making.
But I guess I come back to where I started here, that it is
phenomenally difficult to explain the rationale and logic
for the sorts of treatment management policies that you
feel from the data that we have are most appropriate.
So trust in the doctor becomes vital.
If a patient doesn't really understand things because the
concepts are too difficult or challenging, trust in the doctor
is important. And we know again that if the
patient doesn't understand, if the patient actually doesn't
trust the healthcare professionals advice, they're
very easy prey for the purveyors of snake venom on doctor Google.
Doctor Google will come up with all sorts of brilliant ways to
treat CLL. Does that happen in your
practice very often if you say I'm not going to treat.
You yes, I mean, patients are also in the Internet screening
for some interesting things and they might even find some, some
things like, you know, drink a lot of green tea or things like
this. And I when they asked, it was
one of the frequent questions they asked me is can I do
anything instead of just waiting?
You know, are there any, you know, paramedical things, you
know, paramedicine things I can take?
So that's really good. So rather than waiting for
something to happen, here are a few things proactively that will
benefit you anyway, like exercise and diet and
everything. Excellent.
I'm very glad I'm not a hematologist.
I just actually talk about how you should talk to patients
about these things. But I would like to just step
back again to look at what the levels of anxiety and depression
in patients actually are. There aren't very good data in
fact, in CLL. So any of you out there who are
keen to do some good new projects, I think it's a really
important area to research, particularly because anxiety and
uncertainty, they're very sort of closely linked.
There has been systematic reviews of the data that are out
there. They're not desperately good
because lots of people use different sorts of assessment
measures. But what we do know is that
anxiety is probably between 1/4 and 1/3 of patients that have
measurable anxiety and that's whether they're on what watchful
waiting or on treatment. But depression is about 25%
significantly higher in the treatment group.
Now this could of course be because patients actually who
have to start treatment or further lines of therapy
recognize that their disease is perhaps more serious.
Now I know that there's some interesting work that's been
going on looking at the molecular underpinnings that why
we should really be measuring depression particularly.
There's indeed some early work, and I know that many people are
sitting in this audience being very interested also in
molecular science. I'll just give you 3 examples.
So we know for depression and bipolar disorders, there is a
snip for BCL 2. So the snip Rs 956572 you can
write this down is associated with an exchange or turbulences
in the calcium household and this is associated with.
Depression. So we all know that BCL 2 is one
target in CLL and so it might be worthwhile also studying these
effect. Second example, we know one of
the classics in treatment of depression is lithium.
Lithium increases the BCL 2 levels.
So you might conclude blocking BCL 2 might do something else,
decreasing BCL 2 levels that we know, but also might foster
depressive episodes. And there are other genes, it's
so-called BCL 2 associated ethanol gene, back BAG back one,
back two. It's also associated with
depression. And you don't have to be a super
scientist in order to think that, you know, perturbating the
BCO 2 pathway with our modern drugs.
We might also impact on these kind of this case is a MAPP
kinase, a social pathway that there can be something going
well or wrong depends. But I think we have really to
invest more science also in mental health issues.
We could integrate this in randomized clinical trials to
see whether we really decrease or increase depression disorders
and we could even associate this with molecular markers.
I think this is an interesting topic.
There are in other fields of Cancer Research first tries
investigating this and I would just, you know, just fuss a
little bit. This should also be done in the
CRFL. Absolutely.
I think that's important. And I mean, anything that sort
of effects or improves anxiety and depression can only be
helpful on multiple terms, particularly, as you know, we're
very triumphant about the fact that there's less need now for
chemotherapy. But oral therapies, of course,
do depend on patients taking the pills.
And depressive patients often don't take them.
They don't adhere. So if we can sort of like
summarize some of this, I mean, we could have probably stayed
here all day talking about these things, but I think sort of the
communication side really needs sort of addressing properly and
thoroughly. 1 needs to be empathic and understanding,
which I'm sure you are. But also there isn't like one
set patter that is going to actually fit all patients given
their underlying and pre-existing personality
predispositions. I think being honest is
important, but that demands also offering reassurance and
thinking about the words being used.
You know, I think we should get rid of a watchful waiting for a
start. You're doing active
surveillance. That sounds much more positive
to the patients, but also sort of I think reducing the
patient's uncertainty can only be achieved by sort of probably
again, saying, you know, honestly, honestly, honestly, we
don't want to start treatment until we feel it will genuinely
benefit you. And that's why we will be
measuring things. You don't have to keep on
checking every few hours whether you've got a lump or a sore
throat or whatever. So I wonder if there's anything
you'd like to sort of add to Clemens about what you feel
particularly for maybe younger people who haven't got a lot of
experience in dealing with this concept?
I think it's also the wording very, very important.
So I also never say watch and wait.
I always say watch and live. That's my my expression.
I always say to the patients, you know, if you have questions
after we've talked because questions come later, just give
me a call or just come back to the office to get this kind of,
you know, feedback loop and reassurance on the patient's
side. And I think actually there's
just one little thing I'd add to that also is that I think it's
always worthwhile checking online what the charities, what
are the things your patients are looking at because very often
these don't, they show concordance with what you're
saying and that will increase uncertainty even more.