We will cover the second line really world change completely
with Gardice cells. So Gardice cells now are in
second line with laser cell and axis cell and then in the
accommodation we propose axis and liser cell in second hand
for patients eligible to cartice cells.
So cartice cells are for patients in the collapse and
refractory patients collapse within the first year and then
for the patients that are not eligible for cartice cells
Glofigermux or if you are collapsing really late, you may
eventually challenge the patients with chemotherapy again
and high dose therapy. Please autologous same as home
conditions welcome. To EHE Unplugged, the official
podcast channel from the European Hematology Association
EHE. In this episode we are joined by
Professor Maya Jose Kirsten from Amsterdam University Medical
Center. I'm by Professor Catherine
Teblumun from the Hospitals Only in Paris.
Together, they will discuss the recently published EHA guideline
for the diagnosis, treatment, and follow up of patients with
large B cell lymphoma, LBCL. They're here to give you an
overview of the guidelines and help you navigate the panel's
recommendations. Welcome and enjoy this episode.
Hello, I'm Catherine Tibermo from Paris Sunway Hospital.
Hi. I'm Maria J Kirsten.
I'm from Amsterdam. We worked together very hard to
get this guideline on. We'll discuss all the insurance
and outs of the guideline. So this is guidelines about
largely selling from us and the first step for the the work up
of the patients is about staging the patients.
So, so how do we stage the patients for large B cell
lymphoma? The first thing is to base the
strategies based on the IPI. So we still use this
international pomastic index based on the five factors.
So the age of the patients which is really important, the
interest level, the stage, the number of external sites and the
performance status and the performance status is really the
key to stratify the patients regarding the choice of the
treatment that we will administer to the patients and
make a choice. So the three key factors are
age, personal status and extensions of the disease with
the stage, the external sites and the number of these external
sites. Yeah.
And if we go a step back, because of course first we need
a diagnosis, so we recommend excision of a lymph node.
I think we had a lot of discussion about that.
What's your opinion? Should we do needle biopsies or
should we excise a whole lymph now?
So there is a different school, schools for that and the
technosis is of course based on this biopsy either which was the
surgery or the core needle biopsy.
This is a really easy to take the second strategy and to have
a coordinated biopsy, really easy to get peripheral biopsy,
peripheral leaf node biopsy, profound sites for the biopsy.
And this is I think better compared to the surgery.
Why? Because the surgery make make
will take longer time to get the diagnosis and sometimes we do
not have this time when we treat aggressive disease such as large
be selling from us. If if possible and not too
difficult to reach, I think a whole lymph node is probably
better. Gives you more information on
the architecture. Yes, yes.
So, yeah. And particularly the micro
environment, we know that with the new drugs now we need to
have informations regarding the micro environments.
It's always better to have this surgery biopsy, but if it's not
possible, of course coordinated biopsy is really important and
important step. And what do you think are the
minimal methods that need to be used to get to a diagnosis at
this point? Which methods, immunochemistry
or molecular methods are really necessary?
Yes, of course we need to have between high grade B cell
lymphoma transform from indolent lymphoma as follicular
meshalzone lymphoma as primary B cell lymphoma that are really
particular lymphoma. So we need to have
immunochemistry. We need to have also FISH
diagnosis regarding genes such as Mick B cell 2B cell 6 and to
have eventually the subtypes regarding ABC or GCB which is
not now considered as nobligratory marker because we
know that there is no difference in term of therapy strategies
between AB, CS and GCBS largely selling from.
What do you think of NGS to look at mutational landscape in the
tumor cells? Yes, it's really important and
interesting to have these markers, but right now we have
no difference in term of therapy strategies based on NGS.
I think that we will see more evidence of targeted agents
being more more active for example in the MCD type is, but
this is at the moment not we didn't make it part of of the
guideline because it's not black and white.
So we, yeah, we cannot do this in an evidence base then?
Exactly. Maybe in the next round of the
the guidelines, maybe in the future, in the near future.
I'm sure not right now. Yeah.
And what do you think is the strategy in terms of imaging
diagnosis and for AS into a more end of treatment evaluation?
Yes. So as we said at the baseline,
it's really important to have a good aspect on the extension of
the disease and even the master bulky and to measure the bulky
more than based on the CT scan. But also the PET scan may afford
to have a better evaluation of this bulky mass PET scan at the
baseline. And then the PET scan may also
be repeated with interim analysis after 2 cycles, 4
cycles, and even at the end of the treatment.
So if you are doing interim analysis, you may eventually
skip at the end of the treatment with PET scan and only do ACT
scan. But it's really important to
have a sense of the metabolic response assessment, which is
really important to know if we have complete response.
Do you think that there is several aspect to assess this
metabolic response in term of the?
Yeah. So at the moment I think
standard is that we use the Oval scores or the semi sort of semi
quantitative assessment of the yeah, several shades of Gray.
So and I think that for the moment is satisfactory.
But I think for interim pets we might also start implementing
the delta SUV because it has been shown that if at interim
pets there is more than 70% decrease in the standardized
uptake value, those patients have an especially good
prognosis. I don't think that's implemented
at the moment at most of the hospitals, but I definitely
think Delta SUV and at diagnosis the metabolic tumor volume will
gain the momentum in the coming years.
This effectively is the strategy to evaluate better the patients
during the first line. And so in your opinion what is
the first line treatment for the patients with large B cell in
from us? So the common patients, what is
the best treatment for large B cell?
Yeah. So depends of course on stage.
So for the limited stage patients and low risk factors, I
think abbreviated immunochemotherapy is the
standard. So mostly 4 cycles of Archo.
Maybe we can even go lower with the negative interim path.
But for the stage 2 with Milky disease or stage 3, four, we, I,
I remember we had some discussion about what was the
best first line. And of course again depends on
age, performance status, but also on comorbidities, for
example, the cardio cardiacomorbidities, which would
make treatment with antracyclins more difficult.
But for the standard patients with a low IPI zero to 1, I
think Archop 6 cycles is still the standard of care for, I
don't know now 25 years or more. So we know perfectly effectively
this surface line and based on Archop, what about the high
grade piece of lymphoma because we know that Archop is maybe not
so satisfactory for these patients?
Yeah. So I create lymphomas especially
if they are double hit. And as you know now in the new
DHL classification, this pertains to patients who have a
mid translocation and BCL 2 and it's no longer the MIC and BCL 6
or the triple hits. I think they're with regular
Archop we don't see a good enough outcomes and also the
Polar R chip doesn't seem to be better than our shop in that
particular population. So there we would go in a fit
patient for those just epoch R or another intensified regimen
and also strongly consider CNS prophylaxis.
What about what is your opinion regarding this treatment and to
whom? I would like to administer this
treatment. So in the study, the patients
with an IPI of two to five were eligible for for this study.
So it's a higher risk population and there was a difference in
progression free survive also 6% absolute difference, but no
difference in overall survival, probably because we have good
selfish salvage options with stem cell transplant or Carty in
a second line. So yeah, it's implemented
differently in different countries.
For example in the Netherlands, but I think also in France,
EFOLA is not reimbursed. So we still give our job.
And the last question regarding the first line, but we could
have a lot of more questions. What about this external
disease? Sometimes we have patients with
no involvement or few another involvement but external with
testes for example. And we discussed the past few
years about CNS prophylaxis. So how could we deal with this
prophylaxis and external disease?
I think that's a whole topic on itself.
So much discussion about the use of CNS prophylaxis.
I think most centers have abandoned intrathecal
prophylaxis. So if you think there's an
indication for CNS prophylaxis, I would go for high dose
methotrexate. So at least three grams per
meter square and two cycles and mostly do it at the end of
therapy if there's no CNS involvement.
And of course, it needs patient to do a baseline CSF assessment.
And yeah, so if you look at the extranodal lymphomas, I think
it's best demonstrated for primary testicular lymphoma
because they have a very high rate of secondary CNS
involvement. So we would definitely do it in
those patients. I think the indication for CNS
prophylaxis has shrinked over the years.
And finally, the last one, because I think it's really
important. The strategy is really different
from the other large B cell. Lymphoma is the primary media
cell lymphoma. What is your strategy for this
PMBA? Yeah.
So these are mostly young female
patients who present with a bulky mediastinal mass.
And of course also here direct direct comparison in clinical
trials is lacking mostly. But if you look at the results
of ARCHOP versus intensified ARCHOP like ARCHOP 14 or those
adjusted EPOCH R or other intensified regimens, there's a
clear difference in the progression free survival in
those patients and also very importantly, the rate of
complete metabolic remission at the end of the induction.
And that's really important because in those patients who
still have active disease, you might consider the radiation
therapy, but these are young female patients and giving them
radiation therapy to the chest might also mean an increased
risk for breast cancers. I think achieving the CMR is
really important. I think the i.e.
LSG did a great job in their study demonstrating that in
patients with CMR you don't need radiation therapy and that this
is achieved much more often with intensified recommends.
That was interesting to see that actually our Job 14 performed
more or less the same as even more intensive regimen.
So we have started to we did those just at ebook R, but are
drifting back to our job 14. How about your SO?
This is exactly the same strategy.
We know you, we are using our job 14.
It's really easy and in this population of patients who are
younger after 14 is really and there is no sort of effect,
major sort of effect. So yes, we are.
We switch the two after 14. Yeah, in the primary B cell in
format. Yeah.
And then what do you do in the patients who still have no CMR,
so either the score four or five?
So we can create as you said delta SUV here to be sure that
we are really in not a good response and then we biopsy, we
try to biopsy the patients and we go to second line if we are
not in. Complete response.
Yeah. So you wouldn't go for radiation
in those patients? We prefer depending on how is
the hazardous disease if you have minimal hazardous disease
with many I mean a small sites still involved and if
hyperfixation we may eventually propose a radiation therapy, but
if we have no chemo sensitivity, we will move to.
Yeah, I agree. And I think in this in this
study that I'll study, they also showed that if you irradiate
this DOFIO score 4 cases and there's also a very good
response. But another strategy is just to
wait and repeat the PET scan. Exactly this, yeah.
Yeah, I think we've covered the first line.
And then we will shortly cover the second line that we had
really world that change completely with the gardice
cells. So Gardice cells now are in
second line with laser cell and axis cell.
And then in the accommodation we propose axis cell, laser cell in
second line for patients eligible to CARTES cells and
then for the patient that are not eligible for Cartes cells
and collapsing. So Cartes cells are for patients
in the collapse and refractory patients collapse within the
first year and then for the patients that are not eligible
to for cartesis glaufygmarks or if you're collapsing really
late, you may eventually challenge the patients with
chemotherapy again and high dose therapy plus orthologous
symptoms transportations. So the choice for this online is
really depending on the time of collapse and the sense of how
refractory the disease is regarding chemotherapy.
Yeah. So in the in different countries
this is weighed a little bit differently by also by the HCA
bodies. And for example in the
Netherlands, the patients in the second line who are refractory
or who have early relapse should be transplants eligible to
receive CAR T, which I think is a little strange because they're
not getting high dose chemotherapy.
So they should be eligible for car DI think and not for stem
cell transplant. But yeah, hopefully there will
be the results of the daily two study and we can re discuss this
also with with our healthcare institute in France.
It's not a problem. You can.
Yes, we can effectively use this strategy for how the patients in
early relapse. And then the Sol line that is
really improving with the bispecific antibodies, anti
CD20, anti CD3 with two antibodies available in Europe
and almost all over the world with glofetamab and apreitamabs
of both drugs that are changing. Also the result in third line
for patients with refractory disease after two prior lines.
Yeah. I think in this context, it's
interesting the effort which was done by Florence Prusa together
with the guidelines. We also actually published their
perspective paper in Hemisphere, which was led by Florence.
Actually looking at the availability of all those new
drugs in Europe. She has shown some, I think more
shocking results about clinical trial availability, which is all
very different between a different European country, but
also to access in terms of reimbursement to these new drugs
because there are many countries including ours where for
example, by specifics are not yet reimbursed.
So we're seeing a completely different picture.
Yeah, across, even across Europe, yeah.
Thank you very much and thank you to everybody here to have
listened to us about these guidelines of large be selling
format guided by EHH. Thank you very much.
And thank you to the audience for listening.
And if you enjoyed this episode, please like it and subscribe to
our channel. Stay tuned for more episodes of
EH. Unplugged.