Smilow Shares Greenwich: Lymphoma

September 22, 2021

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Presentations by: Francine Foss, MD Professor of Medicine (Hematology) and Dermatology, Francesca Montanari, MD Assistant Professor of Clinical Medicine (Hematology), and M. Sung Lee, MD Assistant Professor of Medicine (Medical Oncology)

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00:00For joining us tonight on this
00:03evening is a smaller shares a lecture.
00:06Tonight we will be discussing and lymphoma
00:10understanding new treatment advances.
00:13So for many of you who may not know me,
00:15I'm suddenly and one of the uncommon
00:18medical oncologist at Greenwich
00:20Hospital Smilow Cancer Center.
00:22And we are very happy and privileged
00:25to have doctor Francine files and
00:28Doctor Francesco Montanari joining us.
00:30Dr Fauci is a professor medicine in
00:32the section of medical oncology at
00:34the Yale Cancer Center and she is an
00:37internationally recognized clinician and
00:39clinical researcher with expertise in
00:42adult lymphoma and in stem Cell Alley.
00:45Transported transplantation,
00:46she has dried and tested therapies
00:49that have been used to treat thousands
00:52of cancer patients.
00:53And her research has potential
00:55to substantially impact the field
00:58of stem cell research benefiting
01:00patients at Yale and around the world.
01:03That our own Dr.
01:04Mountain Airy joined the our Smile
01:06of Kansas Hospital here at Greenwich
01:09at last year's.
01:10She's an assistant professor of
01:12clinical medicine and cares for
01:14patients with hematologic malignancies
01:16and she joined us from Columbia.
01:19Columbia Presbyterian Medical Center.
01:22Well,
01:22she was an assistant professor of
01:25medicine and experimental therapeutics.
01:27She received her medical degree
01:29from University of Pavia and she
01:32where she graduated Magna ***
01:34Lauda and completed her residency
01:36and fellowship at New University,
01:39where she was awarded the
01:40fellow Year Teaching award so.
01:42A few housekeeping tips before
01:46we get started,
01:48we would like everybody to be make sure
01:49that they're muted throughout the event.
01:51Once we start,
01:52we welcome you to ask questions by typing,
01:55typing them into the Q&A button
01:57at the bottom of your screen.
01:59At any point in the lecture,
02:00and we will save some time at the
02:02end to answer those questions.
02:04Thank you very much for joining us and
02:07let's allow me to get get get it started.
02:21So lymphoma, then farmers are cancer
02:23of or from the lymphatic system.
02:27It is a relatively uncommon cancer from the
02:31annual incidence is about 81,000 new cases.
02:35That makes up about 4% of all new cancer
02:38cases in our country and approximately
02:4120,000 people are projected to die
02:44from this illness this year alone.
02:47So this is just a diagram of what
02:50a lymphatic system looks like.
02:53I'd like to say that the lymphatic
02:55system anyway mirrors our circulatory
02:57system that covers our entire body.
03:00Unlike circuit or system,
03:01though it doesn't have a center.
03:03You know for the circuit or system is
03:05a heart that's the center of it all.
03:06Instead of lymphatic system,
03:08have few key organs such as the
03:10spleen and the famous and the bone
03:13marrow which is not included here.
03:15And I kind of like.
03:17To look at it as a like a subway
03:19map of the New York City are
03:22covering the entire surface.
03:24Start covering the entire
03:26body with nodes like stations.
03:29And cancel that can develop cancer
03:31that develops anywhere in the
03:34lymphatic system would be a lymphoma.
03:36And as Doctor Fauci will discuss,
03:39not only can the cancers
03:41developing these lymphatic glands,
03:42but they can also be found in our
03:45skin as well as mucosal services.
03:48And because of surfaces are
03:49parts of our body that come into
03:51contact with the outside.
03:55When we Christians think about informal,
03:57we divide them broadly into two
03:59separate groups, Hodgkin's lymphoma
04:01and non Hodgkin's lymphoma.
04:03Essentially in a simplistic way based on
04:05where their former selves derived from on
04:08this evening will be discussing mainly
04:11on about the non Hodgkin's lymphoma.
04:14And then on houses in the former can be
04:17further divided into B cell lymphoma,
04:19T cell lymphoma.
04:19And I, I suppose third category would be
04:23something called NK natural killer cell.
04:26Killer cells the that these two
04:31Doctor Montanari will discuss the
04:33advances in B cell lymphoma and doctor
04:36Fossil discussed AT cell lymphoma.
04:39Just a quick word before.
04:42We start our discussion.
04:45As many of you may know,
04:47chemotherapy has been utilized the
04:50treatment of malignancies for UM.
04:54I suppose since the 1950s and until 1997,
04:59treatment for lymphoma has been
05:01fairly consistent.
05:02Component made up of similar type
05:05of non specific medication that
05:07at times could be very toxic,
05:09toxic and in 1997 a new way of treating
05:13the foremost developed a medication
05:16called Rituxan overtaxing map and
05:19thereafter many new advances in our
05:21call in oncology and specific treatment of.
05:24The former has followed and
05:26now without further ado,
05:28I'd like to present Dr Monk Montanari,
05:30who will discuss abuse,
05:32such offences, NPC lymphoma.
05:37I share my screen. So that we can be we want.
05:46Perfect so uhm. I will go through.
05:51Then a new treatment
05:53advances for visa lymphoma.
05:55Uh, my will start just briefly revealing
05:57the classification of non Hodgkin lymphoma,
05:59and then we'll review the treatment
06:01paradigm and what's new for aggressive
06:03in England lymphoma and right now
06:06we're using the word that organization
06:09classification from 2016 and this
06:12is the device for the addition.
06:14There are over 60 subtypes of non Hodgkin
06:18lymphoma and at every provision new.
06:21Subtypes are added up.
06:23I just went up up.
06:25I got your attention that if you start
06:29with selling common follicular lymphoma
06:31this only these two types constitute
06:33more than 50% of non Hodgkin lymphoma
06:37and therefore the other subtypes.
06:40The numbers for the other subtypes
06:42gets smaller and smaller in red.
06:44I highlighted the T cell lymphomas
06:46which are much more uncommon than
06:49the visa and when we think about.
06:52Lymphoma.
06:53We think about aggressive lymphoma and
06:56England comma and this is important
06:59repercussion on the treatment paradigms.
07:02And so when we talk about
07:04aggressive lymphoma,
07:05we think about lymphoma that are
07:08potentially curable with the
07:10intensive immunochemotherapy and
07:12sometimes a consideration with
07:15autologous stem cell transplant.
07:16These are lymphoma that poison an
07:19immediate threat to patients life
07:22and need to be aggressively treated
07:24and when the most common of these
07:27aggressive lymphoma is diffuse,
07:29large B cell lymphoma, that alone.
07:32And constitute a third of all
07:35that non Hodgkin lymphoma.
07:37Uhm, says the most common subtype.
07:39This is only something funny about
07:4125,000 cases per year in EU S and
07:44is usually diagnosed in stage 4.
07:47We are usually considered historic
07:50stratify patients based on design,
07:53international prognostic index based on
07:55age and the age at presentation performance,
07:58status stage,
07:59and number of extranodal disease
08:02psych you see, prognosis varies,
08:05and it is excellent for patients
08:08with that low risk disease.
08:1091% patients are alive for year
08:13after and potentially cured up.
08:16This number gets lower and
08:17lower with additional.
08:18Factors that we need to make things
08:22a little bit more complicated.
08:23Now we know that if you start to be selling,
08:25former doesn't come in one flavor through
08:28the utilization of gene expression profile.
08:31We know that we have germinal Center
08:33B cell like lymphoma and activity,
08:35peaceful life.
08:36That's two main categories of diffusers,
08:39Mr Lymphoma,
08:40that at the expression of different genes
08:42and that translate in a different behavior.
08:44These are survival curves based on
08:47germinal center and activity missile
08:49like and as you see Germinal Center.
08:51Time to do better with current treatments.
08:56As Doctor Lee mentioned at the beginning,
08:59the treatment paradigm for lymphoma and
09:03is relatively old chop chemotherapy.
09:06They want we currently use for these
09:09subtypes of disease has been introduced
09:11in 1976 and it was not until 1997.
09:15Then the taxing on the first
09:18UM monoclonal antibody,
09:19the first targeted drug for cancer.
09:22Was approved as you see here.
09:24Clearly taxi map.
09:25These are the overall survival.
09:27Curves are based on the
09:29international prognostic score.
09:31The risk factors that I showed you
09:33before and after the taxi model.
09:35This survival costs have
09:37been lifted up nicely,
09:39but since then several efforts
09:41have been done to improve further,
09:43more disturbed, and they did not
09:46translate into a new standard of treatment.
09:49Uh, there have been studies
09:52comparing more intensive.
09:54Treatment chemotherapy treatment options such
09:56as those adjusted on April compared to CHOP.
10:00There have been attempts to
10:02incorporate targeted new targeted
10:03agents into the arch of a backbone,
10:06but all these studies didn't
10:07translate in a in a benefit,
10:10and therefore, as of 2021,
10:13this current standard of
10:14care remain are chopped up.
10:17There's a lot of expectation from
10:19the upcoming American Society of
10:21Hematology meeting regarding the
10:23staff regarding the results of a.
10:25Studies comparing your child with
10:28a newer targeted drug with R.
10:30Chop the polarised rider,
10:32but it does not start not out yet.
10:35Uhm, beyond first line of treatment.
10:38So patients that do not respond
10:40or relapse after first line can
10:43still be cure and typically about
10:4420 to 40 patients can cure can
10:47be heard with the chemotherapy,
10:49such as the platinum based or
10:52gemcitabine based chemotherapy and
10:55autologous stem cell transplant.
10:57But unfortunately only a minority
10:58of patients end up liking receiving
11:01this intensive chemotherapy treatment
11:03because of age or comorbidities.
11:05Patients who do not respond to
11:07summer sterope or relapse after
11:09the Alex Cancer transplant are
11:11very likely to die from lymphoma,
11:14so a lot of research has been done
11:17to provide more options to this
11:20patient and over the past five years.
11:23A lot of new option had been
11:25approved as you see.
11:27Here at summarized cymatic antigen receptor,
11:30T cell three products have been
11:33approved since 2017 and then there
11:37are newer drugs targeted drugs.
11:40Three of them are monoclonal antibodies,
11:42two of which are antibody drug
11:44conjugated and one is a small molecule,
11:48and we'll see a little bit more in details.
11:50What are these cameras?
11:52Antigen receptor T cells?
11:53Essentially,
11:54these artists from patients
11:56that are collected.
11:58From and isolated from the blood of patients,
12:00they are sent to facility
12:02where they're sorted.
12:03The engineer the utilizing an active
12:06virus to insert genes and to make
12:09them express a special receptor that
12:12is called the car and undersurface.
12:15Then B cells are extended.
12:17Patient receive an immunosuppressive
12:19treatment in preparation of receiving
12:22these cells to create a favorable
12:25environment for this out to tribe.
12:28And then the sound was there,
12:29infused in the body.
12:31A targeted cancer cell and caused
12:34the death on the the cancer cell.
12:37Nice,
12:38some.
12:38Some of these cells are able to persist in
12:41the body for some for a period of time,
12:43helping with immunosurveillance.
12:45So this is a really knew technology.
12:49And since the approval of the
12:52first party product back in 2017,
12:54which is a second generation,
12:56newer cars have been approved.
12:593rd Generation CARS,
13:00which differs from the second
13:03generation essentially in the
13:05costimulatory as signal and they are
13:08less and less toxic compared to the
13:11first to the first product which was.
13:15Diffusion of diskarte can be
13:17complicated by very severe cytokine
13:20release syndrome and neurotoxicity.
13:22Uhm, but they are able to really
13:26achieve greater results in patients
13:29that are otherwise refractory.
13:31With every factory overlaps disease,
13:34yet therefore tracks that I mentioned to
13:37you up are these at this for for drugs here
13:41three or monoclonal antibodies? As I said,
13:45this is the loading and understood.
13:49Special antibodies are smarter way to deliver
13:52inside the cancer cell chemotherapy there.
13:54What we call antibody,
13:56drug conjugate and essentially the
13:58the drug binds to the surface of
14:01the cancer cell gets internalized.
14:04Lisa Zone released the chemotherapy
14:06agent in the case of political map.
14:09Is that microtubule disruption agent
14:11and that caused a doses of this style.
14:14In the case of longest, took them up,
14:16is an alkylating agent,
14:17so similar mechanism of action different.
14:20Uhm, different target that is see them
14:22up is a antibody and that is a similar
14:25tour attacks in having that is not
14:28drug conjugated and Target City 19
14:30this is the same target of the party
14:33and Salinas are is an interesting new
14:36drug that works totally different
14:38and different way targeted a nuclear
14:41expert protein and that is a media
14:44is one of the mechanisms of Uncle
14:47Genesis and it's preventing diffusers.
14:50Comma, but also in multiple myeloma.
14:53So lot of new option that have been
14:55recently approved in a matter of
14:57two years for diffuse large B cell
14:59lymphoma under flaps refractory
15:01standing up if we shift gears we're
15:03going to talk about what is.
15:05What are the treatment
15:06paradigm for England lymphoma.
15:08So in a little informal trade different
15:11approach to these are incurable disease
15:14and these are diseases that patients are
15:18gonna live with and probably die with.
15:21But not die from and.
15:23So the purpose of treatment is to
15:26minimize succeed city associated to
15:28treatment and maximize the quality
15:31of life producing to the minimum.
15:33The toxicity.
15:36Particular lymphoma accounts for 22%
15:41of all information this than most
15:43common in violently thrown out there,
15:45and the most common treatment
15:47strategies for indolent lymphoma,
15:50particularly comma in particular,
15:51is watch and wait, active surveillance.
15:54We usually do not treat patients unless
15:58they have they meet specific criteria
16:01which refer to as Gulf Gulf criteria.
16:05These are the group 2 the
16:06link from follicular.
16:07Criteria and essentially this criteria
16:09based on the bulk of disease on the
16:13presence of symptoms or end organ damage
16:16in the absence of a buddies indication,
16:19patients are monitored conservatively.
16:21One exception is stage one disease.
16:25It's very rare to diagnose Allen
16:28film and stage one, and in that
16:31instance radiotherapy can be curative.
16:34Uhm?
16:34These are typical approach.
16:37Chemotherapy immunochemotherapy
16:38approaches that we use as first line
16:41treatment for indolent lymphoma.
16:43Once the patient meets this criteria.
16:46Bendamustine rituximab is a very
16:48common regiment that is utilizes
16:50less toxic than our chop.
16:52Patients do not lose their hair
16:55and it costs less
16:57milotic city and the instructions.
17:00Newer version of rituximab and it utilizes
17:03alone or in combination with chemotherapy.
17:06And then there are platforms
17:08that are chemotherapy.
17:09Freeman taxonomically Delight is a
17:11good option as a frontline treatment
17:14for indolent lymphoma based on
17:16their relevance pastry trial data.
17:19Once the patient completes induction then
17:22we typically perform maintenance with
17:25anti CD 20 every three months for two years.
17:29This has been shown to prolong the
17:32remission from first line treatment.
17:34But that's not have a big
17:36impact on the overall survival,
17:38and therefore now in the time in the
17:40COVID era we are limiting the use of
17:43maintenance with anti CD 20 antibody
17:46because these are the antibody
17:48that this antibiotic can cause.
17:50I took an ugly Nina can wipe out the
17:53good antibody that patients mount after
17:55receiving the vaccine for COVID and poise.
17:58Higher risk of infection beyond first line.
18:01So follicular lymphoma,
18:03the Natural History of England.
18:05Common follicular lymphoma is
18:07characterized by multiple relapses.
18:09The duration of Response Times progressively
18:12to decrease after each line of treatment.
18:16There is a particular subset of
18:19patients which accounts for probably
18:2120% of the total and that presents a
18:24relapse of disease within 24 months
18:27from the first line and this group we
18:30referred to as POD 24 disorder patient.
18:33There is a lot of research.
18:35Going on for first of all to try
18:38to the United,
18:39identify them up front and then
18:41to create a treatment paradigm
18:44to improve their prognosis.
18:46But in general subsegment treatment
18:49option for follicular England lymphoma
18:51include another combination of an anti CD
18:5420 antibody plus or minus chemotherapy.
18:57We tend to utilize the same
19:00agents rarely on leave.
19:02The remission has been really long standing,
19:05otherwise we try to alternate views
19:07of the anti CD 20 antibodies and
19:10different forms of chemotherapy and
19:12then learn a little might are square
19:14Lendl made it as if it was not used up.
19:17Trump is a good option beyond Firstline
19:21knew advanced in this field have
19:24been done for third line agents.
19:27We have noble agents that RPI 3K
19:30inhibitors ezh 2 inhibitors and that
19:33Carty also are an option for these
19:36patients beyond the second line.
19:38So briefly, PI3K inhibitor.
19:40This is one of the most important pathway,
19:45a most important intracellular pathway.
19:47A master regulator for cancer is
19:49downstream from the cell receptor,
19:52and since 2014 until most recently
19:54for drugs have been approved,
19:57three or or one is intravenous
19:59and the last one on release it.
20:01It's a little bit different
20:03because it's also targets.
20:04Also seeking one accident,
20:06but we have a lot of options that.
20:09To target this pathway,
20:11another pathway that has been targeted
20:14is that ezh 2 ezh 2 is gonna be
20:17genetical regulator of gene expression
20:19is very important is crucial for
20:22the normal B cell biology and for
20:25the germinal center formation.
20:27A mutation in these each two
20:30suppressed the axis of the visa from
20:34the germinal center and lock the
20:36selling business state and so.
20:39Blocking the each two activity
20:42resumed the differentiation of the
20:45B cell and allow up to system,
20:47and this is an oral drug that has
20:49been recently approved in 2020,
20:51giving another option for patients
20:53with follicular lymphoma.
20:55And, as I mentioned before,
20:56Carti have been recently approved in
20:59March for patients with follicular
21:01lymphoma beyond second line
21:03beyond second line of treatment.
21:08I just wanna mention briefly,
21:10mantle cell lymphoma A.
21:12It's a very rare subtype of lymphoma.
21:15It constitutes only 6%
21:17of non Hodgkin lymphoma.
21:19To retract simitli UM fifty
21:2250,000 cases per year,
21:2555,000 cases prettier in EU S.
21:27And to make things a little
21:29bit more complicated,
21:30comes in four different variants
21:32which we identify based on the
21:35proliferation index and biased allergy
21:38and independent mechanic violent,
21:40we treat as follicular lymphoma and CLL,
21:44but the blast site and aggressive
21:48varien require aggressive treatment.
21:50We use combination of immuno chemotherapy
21:52followed by intelligence concept
21:54transplant and 9320 maintenance.
21:58After a few patients with that in the past,
22:02we didn't have any option because
22:04when this disease relapses
22:06usually chemo refractory but most
22:08recently starting in 2013 drugs
22:11to target the Bruton kinase tiles
22:14and kindness have been developed.
22:17This is an important pathway
22:18downstream from the B cell receptor.
22:21That mantle cell income is very sensitive
22:23to and also chronic lymphocytic leukemia.
22:26Cursor generation on BK.
22:28Emitter approved was brutally in 2013
22:31and shortly after other two second
22:34generation of collaborative events
22:36and Brittany but been approved.
22:38The beauty of the second generation
22:41drugs is that they have a less of
22:44targeted fact and the the cardio
22:47toxicity that was one of the limiting.
22:50Side effect of being routinely
22:52as substantially decreased within
22:54newer generation.
22:55Uh,
22:56there is a newer drug which is
22:58called peer to Brewton if it's still
23:00in clinical trial with the name of
23:03Laakso 305 and is about to be approved,
23:05it is a bit like a mini bitter but
23:07works a little bit different than
23:09the prior one and the beauty of this
23:11drug is that is much better tolerated.
23:16I'm gonna finish here.
23:18I just want to highlight that all
23:22the new drugs that we discussed and
23:25this is this is all these drugs
23:28have been approved and received.
23:30An accelerated FDA approval based on
23:32the results of phase two clinical
23:35trials and it is crucial to encourage.
23:39You can research in this field not
23:41only to improve our current treatment
23:43paradigm and to deepen our knowledge
23:45of specific disease,
23:47but also with the purpose to increase
23:49survival of our patients with
23:51employment to improve their quality of life.
23:56And with this. I'm gonna
24:00stop shooting my screen.
24:21App. I think you're muted Doctor Lee.
24:25We cannot hear you, sorry. Well,
24:28thank you very much,
24:29Doctor Montanari and that was fantastic
24:31and now we will switch over to Doctor
24:35Fauci who is where as I said earlier,
24:38is a world leader in treatment of
24:40T seven former so doctor fast.
24:42If you could tell us So what makes
24:44T cell lymphoma different than
24:46be something formal, deductive,
24:48imaginary had discussed earlier?
24:51Well, Doctor Lee actually everything
24:53up makes T cell lymphoma different.
24:55They'd be selling phomma.
24:57It's harder to treat.
24:59It's rare and you know there are
25:01many different clinical issues
25:03that patients run into that are
25:05slightly different than B cell.
25:07So I'd like to go ahead and do a
25:09brief presentation and I'll try to
25:11touch on some of the key points.
25:13Can we get the next slide?
25:16Renee.
25:21Uh, OK. I think I might be able to
25:24advance them, so I just want to start
25:27off by saying that T cell lymphoma
25:30is a rare disease and a rare disease
25:33requires a center of excellence,
25:35really, for optimal treatment.
25:37For patients, the group at Yale does
25:40represent the center of excellence.
25:42For TSO Info, Ma and I just want to point
25:44out to all the patients and the folks
25:47listening in the audience that it's
25:48not just the doctors that you see here.
25:51Today, giving you this talk that
25:53contribute and help to take care
25:55of you that play a critical role
25:57in your care in the Cancer Center.
25:59Because there are many faces behind
26:01the scenes that are also critical
26:03and important to us.
26:04On this slide you see the path
26:07ologist such as Doctor Hsu,
26:09Dr Katz and Doctor Braddock who are
26:11the folks that actually look at your
26:14slides and make the diagnosis of lymphoma.
26:16And they also help us to subtype the
26:19type of lymphoma and oftentimes.
26:21They do immunostains to identify markers
26:24that help us to treat Doctor Kai is
26:27in the PET scan department here at Yale.
26:31The diagnostic imaging Group and of course,
26:34PET scans are critical to follow
26:35your disease as well as to diagnose
26:38the sites of lymphoma in your body
26:40and Doctor Chi is working with us to
26:42develop some novel ways to use PET
26:45scanning to actually detect residual
26:47disease after chemotherapy and then
26:50of course we have the clinical team.
26:51Myself, Doctor Sethi and Doctor Montanari,
26:55who is presenting today and then
26:57we also have the research group in
26:59the background.
27:00We have Doctor Marcus,
27:02musician and doctor Elias
27:03Loulis who are only two of many,
27:06many folks who are working in basic
27:09science laboratories studying your tissue,
27:11getting samples of blood and tumor
27:13tissue and studying various animal
27:15models of lymphoma to try to
27:17come up with novel therapies.
27:19So really this is a team approach.
27:22Next slide.
27:25So AT cell lymphoma I'll be at rare
27:28is actually increasing in incidence,
27:31so unlike B cells lymphoma where
27:32there are close to about 70,000 cases
27:35in the United States there's only
27:37about 9000 cases of T cell lymphoma,
27:40and there are a number of different
27:42reasons why tastes Alabama might
27:44be increasing.
27:44The first reason may be due to our
27:48pathology colleagues who have developed
27:50techniques to make the diagnosis in
27:52cases where it might be confusing.
27:55In some cases T cell lymphomas
27:57can look like be selling farmers,
27:59and they can also look like
28:00Hodgkin's disease.
28:01So I think some of the increase in incidents
28:03is related just to better diagnosis.
28:06But we also know that certain viruses,
28:08such as the EBV virus and the
28:11HTLV one virus which is found in
28:13the Mediterranean and in Japan,
28:15can be associated with T cell
28:18lymphoma and also the hepatitis
28:20virus and the HIV virus as well
28:22various chemicals in our atmosphere.
28:25Chemicals in our food.
28:27Agent Orange,
28:27which is dioxin perhaps also
28:30contribute to lymphoma in general,
28:32as do immunosuppressive drugs that are
28:34now being used for a lot of different
28:37autoimmune diseases such as rheumatoid,
28:39arthritis, psoriasis, and colitis.
28:40Some of these diseases affect your immune
28:44system in a way where various kinds
28:46of lymphomas could actually spring up.
28:49Celiac sprue is a disease where folks
28:52basically can't eat wheat because they
28:54have sensitivity to gluten and in patients.
28:57With celiac sprue, there isn't an
28:59incidence of intestinal T cell lymphoma.
29:01I'll be it rare and then finally I think the
29:05most common causes random genetic mutations.
29:08Of course, every cancer patient who comes
29:10in wants to know how did I get this cancer?
29:13What did I do wrong?
29:15But the bottom line is that you probably
29:17didn't do anything wrong because many
29:19of these are just random mutations that
29:21occur and those mutations accumulate
29:23and they end up causing cancer.
29:26Uh, next slide.
29:29So clinical features of T cell boamah
29:32and Doctor Lee alluded to this in his
29:35introduction. He selling bombers.
29:37Unlike BSO lymphomas like to go
29:39to different tissues in your body.
29:41In fact,
29:42if you look at various tissues in your body,
29:44there are normal T cells within those
29:47tissues and those normal T cells
29:49are there to protect you against
29:51foreign antigens and infections.
29:53So they're basically fighters and
29:55soldiers that are protecting your
29:57body and they're in the skin.
30:00The GI system, such as your intestines,
30:03the liver,
30:04and the spleen in your nose and
30:06in your sinus is,
30:07and therefore T salambo miss
30:09could arise in any of these sites.
30:11So one common site is the skin,
30:14but I mentioned the intestinal T
30:16cell lymphoma in celiac sprue.
30:18The sinus is and the oral cavity can
30:21be involved in NK T cell lymphoma
30:23and then the liver and the spleen
30:26in hepatosplenic T cell lymphoma.
30:28But pretty much any organ in the
30:30body can be involved.
30:32And if you look at skin involvement,
30:33about 45% of the patients who have
30:36lymphoma in this skin have a condition
30:38called cutaneous T cell lymphoma,
30:40which is mycosis fungus or the
30:43Sezary syndrome and then also I
30:46mentioned that different viruses,
30:47and in particular the EBV virus
30:50can cause the extranodal NK T cell
30:53lymphomas that occur in your sinus
30:55is and a disease called the Angel
30:58immuno blastic to self oma as well
31:00as others and next slide.
31:03Shows you that TICA lymphomas can
31:06masquerade in the clinic as a number of
31:09other different entities or diseases.
31:11For instance,
31:11you may or may not have heard of
31:14him at oh phagocytosis,
31:15which is a condition where you basically
31:17have fevers and low blood counts,
31:19and that is oftentimes seen with two
31:22solemn phomma abdominal pain and
31:24perforation can be seen in patients
31:26who have intestinal T cell lymphoma,
31:29enlarged liver and spleen in hepatosplenic,
31:32as well as other types.
31:34Vasculitis or autoimmune disease can
31:36oftentimes be the first presentation
31:39of angioimmunoblastic T cell lymphoma
31:42and a high calcium level can be seen,
31:45in particular with the HTLV
31:47one associated T cell leukemia,
31:49but also other types of
31:50T cell lymphoma as well.
31:52Kidney failure can occur with
31:54different types of T cell lymphoma.
31:56We can see cardiac arrhythmias happening
31:59and of course various kinds of skin rashes.
32:02So oftentimes a patient.
32:04He selling former will present.
32:08With one of these symptoms
32:10and then eventually,
32:11the diagnosis is made next slide.
32:16Uh, this site just shows you that many
32:19different clinical manifestations,
32:20patients with various skin lesions.
32:23You can see this gentleman with
32:24a tumor at the roof of his mouth.
32:27Below that you can see the lining of
32:29the intestine which is involved with
32:32T cell lymphoma under the microscope
32:34on the opposite side you can see
32:36circulating leukemia cells and you
32:38can see various other skin manifests.
32:40Manifestations that ISE lymphomas are
32:43broken down in the classification system.
32:47Based on how they present clinically,
32:49if they present primarily in lymph nodes,
32:51they're the nodal group.
32:53If they present it in the skin there,
32:55the cutaneous group.
32:56If they present in these various
32:59extranodal sites,
33:00they fall into that extranodal
33:02category and then finally some
33:03of them are leukemic where they
33:06predominantly have circulating cells
33:08in the blood and the next slide.
33:12Shows you the complete classification of T
33:15cell lymphomas and you can see there are lot
33:19of different subtypes of T cell Oklahoma.
33:21So one thing to be careful about if you
33:23have a T cell lymphoma and you're doing
33:26some reading about this disease is to
33:28look more specifically at what type you
33:30have because some of these are indolent
33:32and some of them are more aggressive.
33:35As Doctor Montinari alluded to.
33:37With B cell lymphoma there are many,
33:39many different types.
33:40Then they have different clinical behavior.
33:42But overall, the most common type of T cell
33:45lymphoma are these nodal T cell lymphomas,
33:48and that's in the box.
33:50You can see that that includes PTCLNOS,
33:54which is peripheral T cell
33:56lymphoma not otherwise specified.
33:58Angioimmunoblastic T cell lymphoma
34:01anaplastic large T cell lymphoma,
34:04which is ALCL that could be
34:06out positive or alk negative,
34:08and then the follicular helper and nodal
34:11follicular helper type of T cell lymphoma.
34:13So that comprises a significant
34:15number of our cases,
34:17the next slide.
34:19Gives you an idea of the distribution
34:22of these different subtypes,
34:23and Doctor Montanari showed you
34:25this for B cell lymphoma as well.
34:27You can see that peripheral
34:29T cell lymphoma in the blue,
34:30the angioimmunoblastic in the red
34:33are the two most common types.
34:36The anaplastic large cell lymphomas are
34:39shown in the in the purple at 5 and 6%.
34:42Then you have those NK T cell
34:45lymphomas presenting in the sinus
34:47is the skin and the nasal cavity.
34:50And then in the light,
34:52the light green color is adult T
34:55cell leukemia lymphoma which is
34:57associated with that HTLV one virus.
34:59But the thing to notice about this
35:01is that many of these T solid foam
35:04is are very infrequent, 1 to 3%.
35:06As you can see on the on the left
35:10side of this circle. The next slide.
35:15Uhm,
35:15it shows you the cutaneous T cell lymphomas,
35:18and I'll just say one word about
35:21this disease because Yale is one of
35:23about eight or nine centers in the
35:25United States that sees many patients
35:28with cutaneous T cell lymphoma.
35:30We have total skin radiation
35:33therapy available,
35:34which is only available in a handful
35:36of places around the country.
35:38And that's a key treatment for
35:40this disease as well as expertise
35:42in dermatology with Doctor Edelson
35:44and Doctor Gerardi.
35:45Who are both world leaders in this
35:48area and myself and my colleagues.
35:51Dr.
35:51Dr.
35:52Sethi and Martin Montanari,
35:53as well as our bone marrow
35:56transplant colleagues who see many
35:58patients with this disease.
35:59So cutaneous T cell lymphomas
36:01can occur in the skin.
36:03They can be patches or plaques.
36:05They can be hyper or hypopigmented.
36:08They can occur as tumors as you
36:10can see on this gentleman space,
36:13or they can occur as redness
36:15all over your body.
36:16Which is called the Sezary syndrome.
36:18And again,
36:19this is the most common type
36:21of T cell lymphoma involving
36:23the skin the next slide.
36:28The next slide alludes to
36:31what Doctor Montinari very,
36:32very elegantly talked to you about
36:34with B cell lymphoma and that is
36:37that in order to treat these diseases
36:39effectively we need to really hone
36:41in on what the molecular problems
36:43are and we need to develop drugs
36:46that can specifically reverse
36:48those specific molecular issues
36:49that we find in the tumor.
36:52So there are multiple pathways that
36:55are aberrant or overexpressed,
36:57or perhaps mutated.
36:59That contribute to the malignancy
37:01in lymphoma and and many of those
37:03are shown on this slide and the
37:05important point for this slide and
37:07the reason I'm showing it to you
37:10is that we actually have developed
37:12a program that targets many of
37:14these different abnormalities and
37:16some of the drugs that we have
37:18in clinical trials are shown on
37:20the left hand side of the slide.
37:22I won't go into them in detail,
37:25but many of these are early stage studies.
37:28Phase one such as the Cobra Marson.
37:31Where we actually were among the first
37:33centers to put this into people as a
37:36kind of first in man the tipifarnib,
37:38I'll show you a slide to show
37:40you a responder in that trial,
37:43and then several of these others as well.
37:46Some of these such as TIGIT are novel
37:48immuno therapies that attacked the
37:50actual the T cells that are preventing
37:53our body from having an immune response.
37:56So all of these are important and
37:58again clinical trials are critical.
38:01To the understanding of the disease
38:03and to developing novel therapies.
38:05Next slide. It shows you why.
38:09Perhaps you should consider
38:11participating in a clinical trial,
38:13so this is one of our patients
38:15with aggressive T cell lymphoma.
38:16The peripheral T cell lymphoma
38:18not otherwise specified.
38:20He had advanced stage four disease.
38:22He had our conventional chemotherapy,
38:24which is the first line treatment
38:26for lymphoma.
38:27As you heard from Doctor Montinari,
38:29the chop type regimen is our
38:32kind of our standard therapy,
38:34so this gentleman had that treatment
38:35and then he developed progression.
38:37In his skin,
38:38and if you can look at the pet
38:40the pet scan at baseline,
38:41all of those those white dots that
38:43you see on the arms and the legs
38:46are cancer cells within the skin.
38:48So this gentleman has very
38:50extensive involvement.
38:51He got the tipifarnib,
38:53which by the way,
38:54is an oral therapy that you basically
38:56just take the pill every day and
38:58he had a near complete response.
39:00After eight weeks you can see that
39:03second pet scan showing that almost
39:05all of these spots have gone away.
39:08In only eight weeks,
39:09and then subsequently,
39:11as he got more therapy,
39:12had a complete clinical response
39:14to this drug,
39:15and he moved on to transplant.
39:17So again we have some very
39:19impressive impressive therapies
39:20that were developing the next slide.
39:24Shows you that in addition to
39:26looking at those pathways,
39:28we're also doing molecular studies were
39:31actually sequencing these tumors to try
39:34to identify mutations that can be targeted
39:36again by new drugs and new approaches,
39:39and so by doing sequencing on many tumors,
39:42what we've learned is that there
39:45are certain pathways that seemed to
39:47be a barent in many patients with
39:49specific types of T cell lymphoma.
39:51So in the follicular helper T cell lymphoma.
39:54Such as Angioimmunoblastic and other types
39:57of follicular helper T cell lymphoma.
40:00You can look at the red bar across
40:02the top and you can see that just
40:05about every patient actually had
40:07a mutation in this Step 2 gene and
40:09then below that in the blue you can
40:12see another gene DNMT three.
40:14These jeans are what we call epigenetic
40:17genes and we interestingly have
40:19treatments that we can actually use
40:22to target these gene mutations.
40:25In these patients,
40:26and when we know that and we direct
40:28specific therapies to those patients,
40:30we actually can get very impressive
40:33clinical responses. The next slide.
40:36Showed you some work that Doctor
40:39Montinari did while she was still in
40:41New York before she came to Yale,
40:43so she was working with these
40:46epigenetic mutations and using
40:48drugs like ROMIDEPSIN and a society
40:51Dean to target those mutations.
40:53And so she was participating in
40:56the T cell consortium,
40:57which is a grouping of investigators
41:00around the world who are developing
41:02novel platforms to treat TICA lymphoma
41:05using primarily immunotherapy.
41:07And in this case you can see that
41:09there are combining multiple drugs
41:11and again all of these drugs,
41:13such as azacitidine, romidepsin, develop mab.
41:18These are all drugs that are immunotherapy's,
41:22not specifically chemotherapy.
41:24And again,
41:25they're targeting what we know are the
41:27molecular aberrations in these tumor cells.
41:30So this is really very exciting for
41:32us and the future of treatment of T
41:35cell info may in fact be chemo free
41:37Doctor Moncton. Ari has brought this.
41:39To us here at Yale,
41:41and we're about to actually get
41:43these trials open. Next slide.
41:47Just briefly,
41:47to talk about stem cell transplant
41:49stem cell transplant.
41:50You heard about for B cell.
41:52Lymphoma plays a critical role
41:54in relapse patients.
41:56Autologous transplant involves taking
41:57your own cells and then giving them
42:00back after high dose chemotherapy,
42:02and this is actually used in T cell
42:05lymphoma as part of the frontline therapy.
42:08So when you're first present you get
42:10your chemotherapy and then if you
42:12have a good response to chemotherapy,
42:14we would try to do an autologous
42:16stem cell transplant.
42:17And that would hopefully prolong
42:19their time that you're in remission.
42:21The autologous transplant can also
42:23be used if you've relapsed.
42:25If you didn't have it as part of
42:27your frontline therapy,
42:29and then finally allogeneic transplant,
42:32which involves getting donor cells
42:34from somebody else, a family member,
42:36or an unrelated donor from the
42:38bone marrow transplant registry,
42:40which is an international registry
42:42of folks who are volunteering
42:43to give you their bone
42:45marrow or their stem cells.
42:46The allogeneic transplant.
42:48Is often used for patients with T
42:51cell lymphoma who have relapsed after
42:54autologous transplant but also is is
42:57used sometimes as a first transplant.
42:59For patients with some of those very
43:01aggressive types of T cell lymphoma
43:03and allogeneic transplant is now
43:05being used for patients with mycosis
43:08fungoides and the Sezary syndrome.
43:10Those cutaneous T cell lymphomas we
43:12have a very large experience using
43:15transplant in Tucson Phomma at Yale.
43:18And we're we've published some of our
43:21data which actually looks pretty good.
43:23So both are tollison allogeneic
43:25transplant are ways that we can
43:27cure patients with two solid
43:29phomma and then the last slide.
43:33I'm sorry the the next slide shows
43:36that what happens if you actually do
43:38allogeneic transplant for T cell info.
43:39More patients,
43:40so this is actually a study that was
43:44done with many transplant and T cell
43:46lymphoma centers around the country.
43:48We all put all of our patients
43:51together and we looked at the outcomes
43:53and you can see again that if you
43:56look at that round pie chart you
43:58can see that it's pretty similar to
44:00what I showed you at the beginning.
44:02Many of these.
44:03Patients had peripheral T cell lymphoma,
44:05angioimmunoblastic and cutaneous T
44:07cell lymphoma and you can see that
44:11about 50% of these patients are still
44:14alive at five years and so effectively,
44:17that means that we've cured 50%
44:19of patients with T cell afoma
44:22with alginic transplant,
44:23and I think this is really great news for us.
44:26In great news for patients as well,
44:28what's what what we are doing now
44:31to try to improve on that 50%?
44:33Is we're using other treatments
44:36after transplant?
44:37Hoping to try to augment the effect
44:39of the transplant so that patients
44:41actually do better in the long run.
44:44And finally,
44:45the last slide talks about car T cell.
44:48You taught you.
44:49You heard about car T cell from
44:51Doctor Montanari and again,
44:53CAR T cell is approved for a B cell lymphoma.
44:56It is not yet approved by the FDA
44:58for T cell lymphoma and there are
45:01two different types of car therapy.
45:04What you heard about from Doctor
45:06Montanari is where we take the
45:08patient's own cells.
45:09We take those cells out by a
45:12pheresis and and then we.
45:14Engineer those cells by injecting a
45:17specific gene protein into those cells,
45:19and then we give them back to
45:21the patient in this whole process
45:23takes about three or four weeks.
45:25A newer approach is to use what
45:28we call allogeneic T cells,
45:30and that's shown on the bottom of this slide.
45:32What we do is we get healthy donors.
45:34We take their T cells,
45:36we inject the gene and we manipulate
45:39those T cells so that we can give
45:41them back basically to any donor
45:43and they won't get.
45:45Projected so those are what
45:47we call off the shelf T cells.
45:49Basically,
45:50once we identify a patient
45:51who might need that
45:53kind of a car, T cell therapy,
45:55all we need to do is call the company
45:57order their T cells have them delivered,
46:00which is generally fairly quick and then
46:02go ahead and give them to the patients.
46:04So I think this is exciting for
46:07the future and right now this is a
46:10clinical trial that is open at Yale
46:13for patients with T cell lymphoma.
46:16So I think that is my last slide and I
46:18believe will stop here for questions.
46:20I'll turn it back over to Doctor Lee.
46:23Great, thank you very much.
46:24That was fantastic and it really is exciting
46:27and I just want to echo our two speakers.
46:30And you know all these advances and
46:33and come through research and also on
46:36the research that are being done all
46:38over and of course and hours just yell
46:42in particular and we need researchers.
46:45When patients population and we need to
46:48support and one of the things that we
46:50hope to be able to offer is that with
46:53our hopefully new Cancer Center and
46:56they will have investigational trials.
46:58And then I made available to our community
47:01and our patients in our in our area.
47:04We've got a number of wonderful
47:06questions and Dr Mountain Airy has
47:07I think I answered some of them,
47:08but I have a, you know,
47:10given the age that we live in and I'd
47:13like to ask the two of you a couple of
47:16questions about COVID and vaccination
47:18so you know among your patients at your
47:21tree for B cell and Forman T cell lymphoma.
47:25My first question would be shooed
47:26are of course I'm going to send them.
47:29Our pictures have received and
47:31then the vaccine.
47:32Should they be receiving
47:33a booster vaccine and if.
47:34Yes,
47:35when should they receive it?
47:40Oh I, I can start with the, UM,
47:42you know we shall inform are the most
47:45common treatment that we most common
47:47drugs that we use are antecedent
47:49while yet monoclonal antibodies.
47:51And these are the cells that depletes this
47:54other produce antibodies in our body.
47:56So these are excellent treatment
47:58for the lymphoma.
47:59But the downside is that they sort of
48:03target the same sound that should protect
48:05us from from from from the COVID so.
48:09Patients, yes.
48:10Should that country receive
48:13vision will have cancer diagnosis.
48:15Solid organ transplant recipient
48:17and patient actively on treatment
48:20should be should receive a booster
48:22and and that is that is really
48:26important to maximize their their
48:29production against the bias.
48:32And I also think that we don't understand
48:35enough yet because we're so early in
48:38the evolution of COVID to understand
48:40what really constitutes a good a good
48:43immune response against the virus.
48:44As Doctor Montanari mentioned,
48:46antibodies are critical,
48:48but also we know that T cells play a very
48:50important role and many of our therapies.
48:53Of course, for two Salama deplete T cells
48:56so our patients oftentimes asked me,
48:58well, can I just get that COVID
49:00antibody level drawn in?
49:01Is that going to tell me weather?
49:02Whether or not I need a booster
49:04and and you know, I've talked
49:06extensively to our infectious disease,
49:08folks about that as well.
49:09And the answer is that we actually
49:12don't know yet whether those antibody
49:14titers really mean anything.
49:16And if a patient is immunocompromised
49:18and there as you said, a cancer patient,
49:22the harm in getting a booster
49:24is probably minimal.
49:25The benefit is unknown,
49:27so I generally recommend that
49:28patients do get the booster.
49:31Fantastic thank you very much.
49:33So I have one of the
49:36questions from our audience.
49:40I think will direct us
49:41back to mountain airy.
49:42Do we know what causes B
49:45cell follicular lymphoma?
49:46Or maybe you know you could.
49:48Are there any known risk factors
49:49for follicular B cell lymphoma?
49:53Made in China.
49:54Lisa risk factors for calling for.
49:56In general, anything that essentially
49:59triggers the immune system,
50:01so chronic infection there is a
50:04long list of viruses, bacteria that
50:07have been implicated in lymphoma,
50:09Genesis and more from for marginal
50:12zone infamous subtypes than than
50:15fully pellicular landform itself,
50:17but other neon diseases where your
50:21immune system is dysregulated.
50:24Their setup,
50:25they make patients more susceptible
50:28to develop lymphoproliferative
50:30disorder and finally also
50:33immunosuppressive treatment.
50:34So these are all risk factors
50:38specifically for particular lymphoma.
50:41There has not been any specific
50:44virus or bacteria implicated in
50:46the pathogenesis and as of 2021.
50:52OK, thank you. I have another
50:54question and this is for Doctor Foss.
50:57Here's a patient.
50:58It's president asking the
51:00question I believe is a patient.
51:02What role does age play in selection
51:04being selected for stem cell therapy?
51:07I am 76 and I've been led to believe
51:10that I'm too old for stem cell therapy.
51:13Well, you're absolutely not too old for
51:15stem cell therapy because I have a number
51:18of patients who are in their mid 70s
51:20who've had very successful allogeneic
51:22stem cell transplants. So excuse me,
51:24we don't actually go by age anymore.
51:27We go by what we call a comorbidity score,
51:31which involves basically
51:32assessing how good your heart,
51:34your lungs, your kidneys do.
51:36You have diabetes.
51:38Do you have other medical problems?
51:40And we kind of take all those
51:42factors into consideration.
51:43And so really the decision is made
51:46based on not based on your age,
51:48but based on your overall health situation.
51:52Thank you very much and you know this
51:54next question for Doctor Montana.
51:56I think we were addressed it but
51:57I just want to make sure that this
52:00question is clear since someone
52:01the artist is asking so I will
52:04rephrase this question as someone
52:05waiting a stem cell transplant for
52:09diffuse large B cell lymphoma.
52:11Should I get a booster?
52:13Will it meaning?
52:14The booster would be wiped out by the
52:16process of the stem cell transplant?
52:20So this is one of the
52:23instances where we we might
52:24decide to hold off the booster,
52:26especially if the transplant is imminent,
52:28because even after the booster
52:30it will require approximately two
52:32or three weeks for your immune
52:34system to mount a response,
52:35and by then if you're undergoing the
52:38intensive chemotherapy and transplant,
52:40you might lose the benefit.
52:42Typically, we do recommend to be vaccinated.
52:47After the transplant,
52:48that when your immune reconstitution
52:51happens approximately 3 months
52:53after the stem cell transplant,
52:55that's when we do generally recommend
52:56for patient to undergo vaccination.
53:00And also something I just wanted to mention.
53:03It's critically important in these situations
53:05for family members to be vaccinated.
53:08We've run into that in our transplant
53:10clinic and a couple of instances where
53:13some of the family members have not
53:16been vaccinated and we discussed the
53:17importance of that for the for the patient,
53:20for their loved one.
53:21Who's going to be immunocompromised for,
53:24you know, months and months.
53:25So we really like to stress that to families
53:28that you play a critical role as well.
53:31Thank you, that's great.
53:32I'm glad that you said that.
53:35This next question goes
53:37to Doctor Fauci again.
53:39And I, I believe you've asked
53:41this in your lecture, but again,
53:43I'm really question how does car T
53:46therapy work if you're healthy now.
53:48But if you relapse down the road,
53:51can you have your own cells taken at
53:53the time of relapse or do you need to
53:55have them taken while you're healthy?
53:59Are we talking about car T cell
54:01or stem cell transplant party?
54:03We do not. I mean,
54:05it's an interesting concept,
54:07but we actually do not take your
54:09own T cells unless you're sick.
54:12You know with lymphoma and about
54:14to undergo the car T cell process
54:17primarily because this cost involved
54:19and there's storage or freezing of
54:21the cells may affect the viability
54:23of the cells may or may not be as
54:25good when we need them down the road.
54:27So the answer to the question is.
54:29This moment in time we're not doing that.
54:33OK, next question is reflected lymphoma.
54:38Euro stated that follicular lymphoma
54:40has multiple relapses and measured OK.
54:43Is there also a certain percentage of
54:45patients where no relapse happened?
54:47I? I guess the question is asked in
54:49person is asking what percentage of
54:51people who guess who get a follicular
54:53lymphoma treatment will never relapse
54:55after the first round of treatment.
54:58Yeah, so we typically think about
55:00follicular lymphoma is incurable,
55:02infamous chronic disease where
55:04multiple relapses typically happen
55:06in the lifetime of patients.
55:08UM, stage one is would be additional
55:11would be an exception for that because in
55:14those instances in those rare instances.
55:17It could be curative,
55:19but typically we do expect the disease
55:21to come back at a certain point.
55:24For certain patients,
55:25the tile from treatment until the
55:28recurrence can be very, very long.
55:31It can be decades and the patient
55:35might have other medical problems that
55:38will ultimately be more important
55:40than the particular lymphoma,
55:42but we don't keep think about for
55:44determining format, typically cured,
55:46curveball,
55:47kind of kind of lymphoma with treatment.
55:51OK, yeah.
55:54Thank you
55:55and this. This is a very straightforward
55:58question and I believe there's answer
56:00can be sell the former patients undergo
56:02stem cell transplant and I think as we
56:04discussed in in in our lecture that
56:07investing is the answer's resounding yes.
56:09But again, you know it depends
56:11on your performance status.
56:12You know how you're in.
56:15So, uhm. Doctor fast,
56:18this question comes from someone
56:20that you and I know quite well
56:23and she asked how will you notify
56:25your patience if they are a good
56:27candidate for the upcoming trial.
56:29For patients with T cell T cell lymphoma.
56:35Exception is if someone is still has a
56:37T seven former and undergoing treatment.
56:40How can a patient find out that they may be
56:43eligible for an investigational therapy?
56:45You know, it's let's see if they are
56:47not a patient of our practice, how can
56:48someone find out if they are eligible?
56:50What? What is the typical process?
56:53So if a patient is being seen in
56:54any one of our our care centers,
56:56anyone of the smile care centers
56:58were all attuned to what those
57:00clinical trials are and we all have
57:02a list that we can refer to an.
57:04And it's online. In fact, on the on,
57:07the Yale Cancer Center website you can
57:10actually access what these trials are.
57:12You can ask your physician.
57:14You can always call in and
57:16and talk to to any one of us.
57:18We get calls all the time from folks
57:20who want to know more about the trials
57:22and it might be eligible for them.
57:24We are always screening patients because
57:26we obviously want to give give these
57:28novel therapies to people who need them,
57:30so we're always screening patients to
57:32see whether or not they are eligible.
57:34Patients may not realize it,
57:36but often times before we go in the room,
57:38we're talking in the backroom about
57:40the trials and, you know, looking at.
57:43Various factors like maybe the
57:44crap needs to hire you.
57:46You know your heart isn't functioning
57:47well or you know other issues that
57:49might exclude you from the trials,
57:51but the bottom line is that there there's
57:55information online available to you,
57:57and you're welcome to call and talk
57:59to anybody at any of the care centers
58:01at any time to access the information
58:03about the trials would certainly love
58:05to hear from anybody who wants more
58:07information about clinical trials.
58:10And thank you for the fast.
58:11I think that's absolutely right that
58:14that many patients really don't realize
58:16that behind the scene your clinician,
58:19the research coordinators,
58:21we're all reviewing the records
58:23and to consider whether that person
58:25can be better served through one
58:27of the investigational trial.
58:28And of course,
58:30simply just asking us would be,
58:32you know, we work to come as
58:34the time is running out of this.
58:36If there's one more question,
58:38I think the last question.
58:40If IMBRUVICA only works
58:41for two to three years,
58:43what kind of a treatment is
58:44possible for be selling former?
58:46After I think Dr.
58:47Mountain area answered that,
58:48but I'll let her take another
58:50crack at this question.
58:52Thank you so improving outcome.
58:55Hopefully it's gonna work for more
58:57than two to three years for most of
58:59the patient it has been approved in
59:022013 and there are questions that
59:04are still on the drug from 2013
59:06and now with benefit problem that
59:09sometimes these drugs long term can be
59:13associated with side effects and there
59:15is a drop half due to adverse event.
59:18Luckily to newer drugs have been
59:21developed after IMBRUVICA too.
59:22Sort of offset that problem there
59:25with glass of target effects.
59:27I mean, try to minimize side effects
59:29and making the drug more tolerable and
59:32then mentioned there is a new very,
59:34very interesting drug that is probably
59:37become available soon and just the last
59:40three or five that works similarly
59:42and has a better toxicity profile.
59:45So we have option.
59:47Great, thank you very much and I
59:50believe this brings still close.
59:52Thank you very much Doctor
59:53Foss doctor Martin Eric this is
59:55great and I hope our audience
59:57really got something out of it.
59:59So thank you everybody.
01:00:01Thank you. Thank you. Bye bye.