Translational Science in Hematologic Malignancies

February 25, 2021

Information

February 23, 2021 | YCC Grand Rounds

Presentations by Dr. Stephanie Halene, Francine Foss, Thomas Prebet, and Natalia Neparidze

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00:00Welcome again to Cancer Center.
00:02Grand rounds, good afternoon
00:04and as is often the case,
00:07is always the case in our forum.
00:10We have some really exciting data and
00:13progress and science and clinical
00:16care to share with you in this.
00:18The theme for today,
00:20which is a really interesting one and
00:23different because we have multiple speakers,
00:26is in hematology where we've made,
00:29I think, enormous progress.
00:31And we're both biology translational work,
00:34population science and clinical care in
00:37the major hematologic latency is leukemia
00:41and myeloid malignancy's lymphoma.
00:43Multiple myeloma where I think we have
00:46really talented people working on these
00:50problems and really translating science
00:53into progress for our patients and
00:56looking forward to all four presentations.
00:59But I I will actually turn to our.
01:04Essentially, our leader and host for
01:06the session to make the introductions,
01:09so I'll start simply by introducing
01:12Doctor Stephanie Allyne.
01:13As you know,
01:14Stephanie is the chief of hematology at Yale,
01:18as well as an associate
01:20professor of medicine.
01:22In addition,
01:22Stephanie Overseas the DeLuca Center
01:24for Innovation and Hematology Research,
01:27which is really an exciting
01:29addition to our work in hematology,
01:32with the promise that not only
01:34translating our discoveries
01:36into clinical care innovation.
01:38But also in furthering the support
01:41of our faculty and trainees.
01:44Stephanie joined the faculty in Yale in 2006.
01:48An we were so pleased that she was
01:51selected as our new Chief in 2020
01:53and is doing a great job and looking
01:57forward to her an our faculty
02:00sharing the exciting work at Yale.
02:02So Stephanie I turn to you.
02:07Let me share my slides.
02:11OK, can you see the slides well?
02:14Yes, OK, Alright,
02:15let's tally Saturday will preside,
02:16present or represent on translational
02:18science and hematology.
02:19And there will be four of us,
02:21so I will be the one driving the slide.
02:24So any hiccups blame me.
02:26Um, so I'll be.
02:27I'll be giving a brief introduction
02:29to hematology and then tomorrow
02:32probably will present on behalf
02:34of the myeloid malignancies team
02:36and traumatizing associate,
02:38professor of medicine,
02:39hematology,
02:39and he's a director of the MLP
02:43malignancies disease team and
02:44the firm chief of the data firm,
02:47and everybody knows just how
02:49much moving Anan changes had to
02:52happen over the past years to
02:54keep our clinical services alive.
02:56And to my actually completed his
02:59doctor rent in medical hematology oncology.
03:02Myung then joined the Paoli
03:04Calmettes's Institute in Marseille
03:06and did a full ride scholarship
03:09at Johns Hopkins University,
03:10and I think that's how eventually
03:13he landed with us.
03:15With Steve Gore recruiting him.
03:17After tomorrow, Doctor Francine Foss,
03:20Professor of Medicine and
03:21hematology and Rheumatology,
03:23would present on behalf
03:25of the former team and.
03:27Francine really is the expert in
03:29T cell lymphoma, internationally,
03:31nationally, renown,
03:32and she's a research director of an
03:34informal disease team and obviously
03:36director of the Tucson Informer program,
03:38and you will hear exciting news
03:41what is happening in the format to
03:43selling Thelma and last but not least,
03:46doesn't Italian infrared,
03:47so will present on behalf of the
03:49multiple myeloma disease team.
03:51And she's the research director
03:53of the much more disease team
03:56and an assistant professor in.
03:58Medicine medical oncology.
03:59She actually obtained her medical degree
04:01in Tennessee and the country of Georgia,
04:04then did postdoctoral fellowships at Emory
04:06Northwestern and Lucky for us a deal.
04:09She did her residency and fellowship.
04:11Odiele refill Oscar left us,
04:13but we were able to recruit her
04:16back to be part of the team.
04:19So um,
04:19before I introduce much about hematology,
04:22I think it's absolutely time that
04:24we all say thank you to Charlie.
04:27So Charlie,
04:27you took over as our interim
04:30section Chief in January 2018
04:31and has been a just wonderful,
04:34wonderful journey since then.
04:35So you can see just how big the
04:38group is in hematology and growing.
04:40And I just want to read a few
04:43of the quotes from our faculty.
04:46And that is so Charlie,
04:48you recognize the strength,
04:50resilience and enthusiasm in
04:51the new teologi faculty, staff,
04:53advanced practice providers,
04:54nurses entry needs,
04:56and you supported our teams in so many ways.
04:59Thank you for the leadership and
05:01commitment you provided as interim Chief.
05:04Your strong support and advocacy
05:06for our section is not appreciated.
05:09Thank you for being an outstanding
05:11leader and role model for trainees
05:13through your dedication to
05:14excellence in patient care,
05:15teaching and innovation.
05:16It has been an honor to learn from
05:19you and the excellent faculty of
05:21your Cancer Center and thank you
05:22for everything you've done for the
05:24Cancer Center and was a section of
05:26hematology over the past several
05:28years. You have been a wonderful resource
05:30and a guide from my academic growth,
05:32and I'm extremely grateful to you.
05:34So thank you, Charlie.
05:37Thank you in the entire division.
05:39It's a real point of pride to me
05:42to have been a member and now and
05:45along of this very August center
05:48of excellence. So thank you.
05:52And we have a little bit more in store,
05:55so the thing we really wanted to thank
05:57you for is how you have supported all
06:00our people and recruitment of all
06:02these people highlighted in yellow.
06:04You know Murrayshall is to my like
06:06my name is this team chilling costar
06:09Intercine safely to the lymphoma team.
06:11Barbona is our director of classic
06:13hematology, Sabrina Browning as a member
06:15of our myeloma and come up as a team.
06:18And as you can see,
06:20also of our billing team.
06:22And then in addition to that,
06:24you have recruited hematology
06:26focused faculty to the to the Smiler
06:28network and the care centers,
06:30and we're so fortunate to work
06:32with all our colleagues.
06:33And of course Mike's mission as a director
06:36of the Center for Molecular and Cellular.
06:38I always say hematology and oncology
06:40in there were so excited about,
06:42you know, all our new people and teams
06:45and what we can achieve together.
06:48So, um,
06:49so now in my introduction to hematology.
06:51So what you see here is kind of our.
06:54These are hematology core teams.
06:56I say core because these are the
06:58people located in in New Haven,
07:00North Haven.
07:01And these are the teams that are
07:04working hard to bring the best patient
07:06care to all patients in Connecticut
07:08and beyond through their research
07:11that clinical care and collaboration
07:13was all the teams we have smile.
07:16Oh yeah, even health and University.
07:18So we have five teams in my life
07:21malignancies team, an informer team,
07:23the stem cell transplant,
07:24and South Therapies team.
07:26We call it classical hematology
07:29because as we all know.
07:30Behind him, disorders are not that denied.
07:33Our patients are quite ill and then our
07:35minds from my Loma and commodities team.
07:38So as I mentioned before,
07:40we're not alone.
07:41We're not just a small,
07:42tiny little point on the map in New Haven,
07:46but through our smaller network we
07:48have reached across the entire state
07:50and it is just wonderful to know that
07:53we can bring the excellent signs and
07:55treatment to all patients in Connecticut.
07:57Then again,
07:58here I'm highlighting our
07:59hematology focused faculty,
08:00which is also new over the last.
08:03Several years and it's just wonderful.
08:07How much team building we can do?
08:09There are many discussions already going
08:12on between our disease team leaders
08:14and faculty and tremble in North Haven,
08:17Guilford, Hardford and all the other places.
08:19So it's wonderful opportunity.
08:22Um,
08:22we're not alone and we're not
08:25doing this in isolation,
08:26so we're fortunate to be at a
08:29place like here where there are
08:31many different centers there.
08:33We have our Decker Jews tallied
08:35in the clinical Trials Office.
08:37Again,
08:38Marcus leading that CMC L Michaels
08:40bosenberg leading yell center
08:41female oncologix Mark Lemon,
08:43leading the year Cancer Biology
08:45Institute kinda Neugebauer,
08:46leading the Larne Center.
08:48And then Diane Krause in the my C Age
08:52and then cheers of the different departments.
08:55Chengdu for pathology.
08:56David charts now Department
08:57we know immunobiology.
08:58We have collaborators in
09:00the stem cell center.
09:01We have collaborators in the Copper center.
09:04Marcella Nunez Smith just gave a
09:06talk to to the leaders this morning
09:08and Antonio riders and many,
09:10many more that I can't even
09:12get on this slide.
09:16So, um, I just wanted to give a brief
09:19update on the Delucas Center for
09:22Innovation and Hematology Research,
09:24another amazing initiative that Charlie
09:26made happen and we are now we've just
09:29riding our progress report for the past
09:32two years and just to give you an update.
09:35So we have a very active hematology
09:37tissue bank with samples from patients
09:39with all human to logic disorders.
09:42We have over 4000 samples from over 2000.
09:45Nations, we have a bone marrows prefer blood.
09:48We're working **** ** also collecting lymph
09:51node tissue and other tissue biopsies.
09:53And we also offer specialized processing
09:56for clinical trials in hematology.
09:58And this is again a huge.
10:00Team effort so you see our core people
10:03on the right and Michelle Patel,
10:06rounder, Feli,
10:06Padma Mamillapalli and our latest
10:08recruit Jennifer from donor Hoban.
10:10But everybody in hematology
10:12is contributing to this.
10:13All our aips an MP7 in North
10:16Haven at Trumbull.
10:17Another care centers and we hope to leverage
10:21this tissue bank to better understand
10:23these users and offering treatments.
10:26We have awarded 9 pilot
10:28grants or $50,000 each.
10:29Our goal is to have these being
10:31through these be collaborative between
10:33collisions and basic scientists.
10:36We have one career development
10:38award E chaining cathari.
10:39These are two year awards and the
10:42our base posted for new applicants.
10:45We have many many applications
10:47publications that I could not list here.
10:49We have installed the freezer
10:51works by repository database and
10:54we're very close to populating it.
10:56This data that eventually will allow
10:58clinician scientists in a deidentified
11:00manner screen what we have in the
11:03database so they can come up with ideas
11:05and let us know how we can help them.
11:08We're providing access to novel technologies.
11:10Jennifer Amisha Jazz performed single
11:12site DNA sequencing for clinical
11:14trial samples for to Maccabean.
11:15We have many more ideas and we are also
11:18seeking to provide Technical Support for
11:20correlative studies and data analysis.
11:24So let me now go over to the disease teams,
11:27so this these are the members of the stem
11:29cell transplantation cellular therapies team,
11:32but they will not present today
11:34because you should stay tuned and log
11:37into the Young Cancer Center grounds.
11:39I think it's March 23rd when
11:41Doctor Supinder for her with her
11:44present on cellular therapies.
11:46You will also not here today from
11:48our classical hematology team,
11:49because Doctor Boner just presented
11:51not so long ago in grand rounds.
11:54But we're also very hopeful to getting
11:56a slot in the summer when we will have,
11:59hopefully exciting new recruits
12:01to add to the team.
12:02And we can take a full grand
12:05rounds for our classic hematology.
12:08So the team you will be hearing from today.
12:11The first one is on myeloid
12:13malignancy's team and Doctor Priebe
12:14will present on behalf of this group
12:17and so now I'm heading over to Doctor
12:19Kirby for the first presentation.
12:22OK, thank you. Thanks a lot Stephanie,
12:25for this really kind introduction.
12:27Within blessed to have
12:28already Nikolai in myself.
12:29Within single, fewer a few weeks
12:32ago on this ground round and I
12:34guess that you know probably most
12:36of the members of the team already.
12:39That on our side and that any color without
12:42self on universe recruit Rory share is.
12:46Doctor Brokaw from San Francisco
12:48and up to it from Trimble that
12:51collaboration is basically something
12:53that is extremely important for us.
12:56And on the translational abside Stephanie
13:00for sure that has been instrumental in
13:03in the group as well as Manoj Pillai.
13:07Next slide, please.
13:11So as you may know,
13:13in MLP malignancy daughter asked
13:15basically 10 years we had a real
13:18paradigm shift thanks to the
13:20revolution of our understanding
13:22of the genomics of the disease.
13:24That's been true in acute myeloid leukemia,
13:27so that's really fast.
13:32Through in the acute myeloid leukemia.
13:35Then in my dysplastic syndrome,
13:38but is basically representative
13:40of what we have seen also in our
13:45knowledge of my wife, activities,
13:47orders, or bone marrow failures,
13:49for example, and this revolution,
13:52in our understanding of the disease,
13:55translated more recently.
13:57And we can switch style.
14:01Um, in a boarding shift also in the
14:05management of this disease and since
14:082017 we add more approval than over
14:12the last 2025 years that goes with
14:16basically drug at R agnostic of any.
14:20Potential genomic amenities such
14:23as the CP351 for example or more
14:26recently than 8:00 o'clock,
14:29but also drug that are no standard of
14:32care for basically mutated diseases,
14:36such as flat 3 mutated AML or,
14:40potentially IDH mutated diseases.
14:42Interestingly, this revolution that
14:44started with the access my leukemia,
14:48we're starting to see seeing,
14:50speaking up.
14:51Also, in multiple packages,
14:53orders with the recent approval of
14:56Fedratinib as well as with my dysplastic
15:00syndrome with recently the approach
15:02the TGF beta inhibitor spider step
15:05as well at the oral decide to be in.
15:10Stop all of that is extremely
15:14important and allow us to basically.
15:19Have a real improvement for or
15:21patient regarding prognostic
15:23forgetting option of treatment.
15:25But we still in situation where a cute smile,
15:29leukemias and melodies plastic
15:30syndromes are how to treat disease.
15:33If you standardize the incidence
15:35rate of looking at my leukemia,
15:38that's still in the top five of
15:42the most deadliest cancer that
15:44we have to face in the US and one
15:48of the goals that we had.
15:51In the group has been to really work
15:54at different aspect to try to improve
15:57the result of the different treatment
15:59and we can switch to the next slide.
16:02Uh,
16:04and.
16:05We really tried to to work from
16:08single cell to population research
16:11and population outcome and that's
16:14just not basically to to to to
16:18basically have a stun.
16:20But that's really what is the
16:23MLP malignancy group going from.
16:26Stephanie was mentioning our first
16:28result in a single cell sequencing
16:31in acute myeloid leukemia.
16:33As the researcher Stephanie Ann manner.
16:37In the labs around uh. Mouse model of.
16:44Testing syndromes RNA for montage
16:46to the collaboration that we have
16:50with the Cobra Group,
16:52led by AMR Nikolai and Rory on
16:57outcome research.
16:58From a pure clinical research,
17:01sense points or group has been
17:04instrumental in several key studies
17:06that led to approval of these
17:09drugs over the last few years,
17:12but or portfolio and our goal is really
17:15focused on early development of a new agent.
17:19Right now click portfolio is
17:22roughly 40% of phase one trials.
17:27With.
17:29Basically a good #6 out of 19
17:31active trial that our investigator
17:34initiated trial and thanks to all
17:37the commitment of the research staff.
17:40Thanks to all of the commitment
17:43of the different members of Group
17:45we right now at a rate of index
17:48cases included in clinical trials
17:51on main campus that is 15 to 20%.
17:55Which is pretty remarkable.
17:58We definitely aim to do better and
18:01we definitely aim to be able to
18:05export the research we're doing from
18:08the main campus to different side
18:11of the network and be able to add
18:15better access for our patients in the
18:18network as mentioned by Stephanie,
18:21we have pretty efficient and pretty large.
18:25Think annotate by bank and I think
18:28we can give kudos to Stephanie
18:30to each of the exports in 2011,
18:33so we're in a decade in right now.
18:36We should definitely celebrate about that.
18:38And that gives us a lot of leverage,
18:41potentially to be able to develop some
18:44translation translational research.
18:45As well as potentially bringing
18:48some collaboration from the outside
18:51with pharmaceutical companies as
18:53well as from academic centers and
18:56go to the next next slide.
18:58Just wanted to highlight basically two
19:00programs more than two studies to program.
19:04Basically going on the first one are the
19:07efforts led by armor side and on emerging
19:10approaches in my late malignancies
19:13and probably Anna does not remember,
19:16but I've even.
19:18Remember first discussion years ago
19:20when we were in Hopkins together
19:23around potentially all this knew,
19:26you know therapies can be instrumental
19:29in or disease disease type, basically.
19:35What has been done is basically
19:37around the additional,
19:38uh,
19:39the 1st generation,
19:40but also right now the second
19:42generation of even the energy agent
19:45to conventional conventional therapy.
19:47We're right now activating.
19:51Very broad induction chemotherapy plus volume
19:55up study under the umbrella of a sitter.
20:00With the first patient that we hope
20:04to include in the next few weeks,
20:07we just have finished the,
20:10uh,
20:10cool on the map plus entinostat NDS
20:14trial for the group of patients with
20:17mild ******* agent Majestik syndrome
20:20failed by accommodating agent,
20:22and we are looking forward for
20:25this data that has been basically
20:28possible to to develop thanks to.
20:31Elaboration with Yale Science and
20:34that's work with initially TK came.
20:37One of us still here and we have also a
20:41chronic my leukemia studies sponsored
20:44by equal on the addition of bambrough
20:48on tyrosine kinase inhibitor for a
20:52patient with chronic migraine leukemias,
20:55an Axia Resul disease.
20:58Beside this trial,
20:59we also have been implicated.
21:02Basically thanks to our leadership
21:04on some of the development of the
21:07newest generation of Elon College.
21:10Agents such as the T in three inhibitor
21:14and we hope to have more results to to
21:18show that in the near future next slide.
21:22So the the idea hmm DS program?
21:25That's something that I already.
21:28Presented basically a few weeks
21:31ago during the ground rounds,
21:33but I definitely like this program
21:36as it's really a homegrown program
21:39thanks to the work and interaction
21:42with Stephanie and Ranjit.
21:44So that's really a good example of what
21:48we can achieve at at yell working together.
21:52We have been able to show how
21:56we can exploit the weaknesses
21:59of IDH mutated AML in NDS.
22:02As you can see.
22:05When we have an idea of
22:08mutation and the presence
22:10of two HG in the media that creates
22:14some braknis phenotype that can be
22:17potentially targeted by using popped
22:20inhibitor on the upper right side.
22:24Can see that treatment with olaparib
22:27in a primary samples in grafted in
22:30mice can potentially significantly
22:33reduced the disease burden in.
22:35Lisa grafted with acute myeloid leukemia.
22:39Presenting an IDH mutation including in
22:44some samples where we already documented
22:48the resistance to IDH inhibitors in the
22:53clinic and that led to the step trial.
22:58Brentley ongoing with right now.
23:01Six patient included,
23:03including four at.
23:06At here with basically the use
23:09of elaborate the parking meter.
23:12For a male and MBS patient with IDH mutation.
23:17Interestingly,
23:17for the discussion with the tap,
23:20we've been able to have a patient that
23:24were not yet exposed to IDH limit,
23:27or potentially integrating the trial
23:30with an early evaluation that would also
23:33potentially to switch to ID age limit,
23:36or there was no some clearcut benefit
23:39after a few weeks on treatment, so.
23:43That's two of the main program
23:45that we have right now.
23:47I'm not going to basically talk
23:49too much about the outcome.
23:51Research as we we add with basically.
23:55Nicole,
23:55I would review of what was going on
23:59on this Group A few a few weeks ago,
24:02but as we were discussing we really
24:05want to be able to to bridge the
24:08most basic science aspect of it.
24:10What we're doing in the in the labs
24:13to this outcome. Research go go ahead.
24:18We still have a lot of people
24:20in the results clinical issue.
24:22Then that's the topic.
24:24We're not the addressing all of them,
24:26but some of them are definitely
24:28on the focus of the group.
24:31The management of high risk disease
24:33in AML and MD S complex karyotype.
24:36NLL mutated or rearrange disease are one
24:38of the focus of development of the group.
24:41And I specially Rory is developing
24:44some different concepts around.
24:46These lines,
24:47the optimization of targeted
24:48therapies and email steropes.
24:50We talked about that one of the challenges,
24:53basically that we're still working
24:55with the disease that is not as
24:58common as breast or colon cancer,
25:00and we end up with more combination
25:02and sequence of agent then patient.
25:04And that's potentially where
25:06the interaction with the lab and
25:08the work that we're doing with
25:10Stephanie is extreme and mineral.
25:12Extremely important.
25:15Targeting of leukemia stem cell looking
25:17initiating cells and management.
25:19Measurable residual disease at
25:21the molecular level is obviously
25:23something that is on our mind,
25:25and that's a lot of interaction.
25:28Also with the transplant group in
25:30South Therapy Group on our potentially
25:33to to work around this concept.
25:35And last but not least,
25:38before getting to the point where
25:40we have active disease,
25:42working on predisposition
25:43and potentially climb.
25:45To please,
25:45this is something that is extremely
25:48interesting right now with.
25:49In collaboration we will have.
25:52With the cardiology group
25:55and the Generation project,
25:57I think I have one last slide, so we.
26:02Feel that we we're pretty blessed in the
26:06group to have already's.
26:08Pretty solid foundation,
26:09but we wanted to do better and that's
26:13gonna be by leveraging the excellence
26:15that we have it here the molecular
26:18biology aspect with basically right
26:20now are some development in single cell
26:23sequencing using multi omics approaches
26:25that can potentially be used in my life
26:28but not only in my right mind agencies.
26:31Potential collaboration and avenues
26:33of collaboration with the yellow.
26:35Center of immuno oncology.
26:39And with a group of Marcus mention also to
26:43potentially work on resistance disease,
26:45immuno oncology in my redemer agencies
26:48and the really fruitful and really
26:52exciting collaboration we have with
26:54the Copper Group carry gross schalmei.
26:58With a lot of publication and lots
27:01more that will come in the next.
27:04Month and year.
27:05We want to expand our collaboration.
27:07That's going to be more collaboration
27:10and the basic Science Group partners
27:12like June Liu Shan Quinn Go are
27:15definitely people that will be more
27:17and more on the stage with us in more
27:20portable computers as well as more
27:22collaboration on the clinical research side.
27:24Obviously with the BMT
27:26and cell Therapy Group,
27:27but also without regard for
27:29the adolescent young adults,
27:31and I think that's all I have.
27:35Thank you so much tomorrow.
27:36This is really awesome,
27:37so we'll go straight into our next
27:39presentation by Doctor Falls on
27:41behalf of Mylan Malignancy's team.
27:45Hi, this is Francine and I'd like to
27:48thank Stephanie and also Charlie for all
27:51of your work to bring us to where we are
27:56today with this faculty on the development
27:58that we've had in the lymphoma program.
28:01So lymphoma program consists of myself,
28:04Scott Huntington, ERISA, Soupy,
28:06Shalin, Kothari, Toshin Sethi,
28:07an Francesco Montanari,
28:09both of whom have recently joined us.
28:12Francesca is in Greenwich.
28:15Next slide. Um?
28:17So this is the landscape of lymphoma.
28:21So lymphoma really is many different
28:23diseases, and that's a challenge for
28:25us as a group with limited resources.
28:28Terms of trying to figure out how
28:30we focus this clinical trial effort.
28:32So it turns out that out of the 21,000
28:36cases of cancer in Connecticut per year,
28:38there are about 900 plus or minus
28:40cases of non Hodgkin's lymphoma.
28:43So that's really our denominator
28:45population in our efforts are to
28:47try to get many of these patients.
28:49Want to clinical trials?
28:50If you look at the curve at the
28:53bottom you can see the frequency of
28:56the different types of non Hodgkin's
28:58lymphoma with diffuse large B cell lymphoma,
29:01follicular lymphoma,
29:02the low grade marginal zone lymphoma
29:04is being the most common subtypes,
29:06and T cell,
29:07lymphoma and mantle and mantle
29:09cell lymphoma and burqas are.
29:11You can see are rare compared
29:13to these other common subtypes.
29:15Next slide.
29:18Um, so the unresolved political issues,
29:20of course,
29:21are how we make sense of 90
29:23different subtypes of lymphoma and
29:25divide those into general themes.
29:27For clinical trials,
29:29I'll talk a little bit about
29:31that in a minute,
29:33but you know,
29:34we do have diseases where the
29:36modern regimes pretty much are OK
29:38in terms of producing favorable
29:40outcomes for these patients,
29:42but there are within these more
29:44favorable subgroups of patients.
29:46Those patients with high risk molecular.
29:48Features that continue to fail
29:50conventional therapy and would be
29:52subjects for novel clinical trials
29:54and those include double hit diffuse,
29:56large B cell lymphoma and
29:58one of the things that we.
30:00Done with that disease is to combine
30:03dose adjusted epoch with Lenalidomide.
30:05In addition,
30:06we have some patients with low risk
30:08lymphoma where we could actually
30:10test D escalation of therapy and a
30:13good example of that is classical
30:15Hodgkin's disease and I'm going
30:17to show you another example.
30:19For diffuse large B cell lymphoma
30:21we also have histologies where the
30:24modern regiments are in ineffective,
30:26pretty much inadequate for these
30:28aggressive patients such as
30:29the T cell lymphoma's.
30:31The piece of distributing mantle cell
30:33lymphoma's and the post transplant
30:35lymphoproliferative disorders so
30:36in these cases where are trying
30:39to incorporate novel agents into
30:40the frontline but also trying to
30:43figure out how to incorporate
30:45allogeneic stem cell transplant and
30:47the newer car T cell therapies,
30:49would love to use molecular and
30:51genetic profiling in these diseases
30:52to select patients rationally for
30:55pathway directed clinical trials,
30:56and those efforts are now underway
30:58thanks to the work of Stephanie.
31:01To get our tissue bank up and running.
31:05Sorry sorry, OK next slide.
31:09So, um, just touching on how
31:11we're deescalating therapy.
31:12This is a really great example of a
31:15trial that Scott has opened for relapsed
31:18aggressive B cell lymphoma's where
31:20we have a non chemotherapy approach.
31:22So basically this study involves oral
31:24agents of BTK inhibitor and mtor inhibitor,
31:27an an image, and it turns out that when
31:30you combine these three oral therapies,
31:33this is a very effective strategy for
31:35patients with aggressive lymphoma who
31:37have failed conventional chemotherapy.
31:39Some of them have failed transplant as well.
31:42On the next slide, Stephanie,
31:44you can see an example of one
31:46of our patients.
31:47It turns out that yell actually has
31:50involved the majority of patients that
31:5221 patients to date in this trial and
31:55responses have been observed among
31:57a different subtype of patients.
31:59You can see with DL,
32:00BCL with low grade lymphoma,
32:02mantle cell lymphoma etc and patients
32:04with very dramatic responses with
32:06large masses and extensive disease.
32:08So we were really excited about
32:10this approach.
32:11And again,
32:12we'd all like to start thinking
32:14more about oral rather than Ivy
32:16therapies for patients that are going
32:18to be chronically needing therapy,
32:20such as many of our lymphoma patients.
32:23Unfortunately,
32:23next slide would highlight another approach,
32:25which is to take an active drug,
32:28look at its resistance mechanisms
32:31and come up with.
32:33Similar drugs that might be active
32:35in resistant mutational settings.
32:36In this case.
32:37BTK inhibitors are one of our most
32:40active newer agents in B cell lymphoma,
32:43but most of the failures to these
32:45agents are related to the development
32:47of specific mutations and now we
32:50have these new non covalent BTK
32:52inhibitors that actually are able to
32:55subvert those mutations and induced
32:57responses in patients and this is an
32:59agent that we're working with now.
33:01Locks 0305.
33:02Falls into that category that's
33:04highly active.
33:05We are currently embarking upon a
33:07number of phase two studies that
33:10we hope to make available broadly
33:12across our care centers looking
33:14at a number of different B cell
33:16lymphoma is with these novel agents.
33:18Next slide.
33:21Um,
33:21this is some interesting work and
33:24translational research done by
33:26shelling pathari in our group.
33:28So Charlyn is looking at ways of.
33:31Dealing with the development of
33:33resistance to active agents such as phonetic,
33:36LAX,
33:36and hear a set of experiments where
33:38he has shown that proteasome inhibition
33:41is synergistic with phonetic lacks
33:43in patients with B cell lymphoma an.
33:46In these clinical models,
33:47so you can see the bot is mid carve.
33:51Is Mebane exacerbated by themselves,
33:53which are proteasome inhibitors have
33:55some activity to induce a pop ptosis?
33:57As does phonetic LAX?
33:59But when you combine these agents
34:01you can see synergistic activity.
34:03And based on this in vitro
34:06work that Charlene has done,
34:08he's embarking on a seat
34:10app sponsored Phase 1,
34:12two clinical trial where he's
34:14combining genetic LAX with these
34:16proteasome inhibitors and we're very
34:18excited for Shaolin to get that trial
34:21up and running on the next slide,
34:23you can see the correlative science that's
34:26he's developed around this clinical trial,
34:28including a single celled Association
34:30to look at these specific BCL,
34:33two family members.
34:34By Aqua, as well as by mass spec.
34:37He's also doing exome sequencing,
34:39RNA seek and trying to obtain tissues from
34:42these patients for later PDX development.
34:45So that's all very exciting and we're
34:48really proud of shelling for that.
34:50In additional, he's he's doing what other
34:53groups are doing to embark on looking for
34:56a circulating tumor DNA in these patients,
34:59and hopefully some of us will be
35:02able to incorporate that into our.
35:05A disease group studies as well next slide.
35:09So and then the last thing I want
35:12to mention is exciting work that
35:14Charlene is doing with the Cats lab
35:17to use a different approach called
35:19protest back to target antiapoptotic
35:21protein proteins potentially,
35:22but their critic benefit soap Protex
35:24basically is a hetero bifunctional
35:26small molecule that consists
35:27of a linker and two warheads.
35:30One of them binding to the target
35:32protein such as the BCL two and the other
35:35recruiting the E3 ligase to basically
35:38leads to the degradation of that.
35:40Protein,
35:40so we're looking forward to this work coming
35:43to fruition in the clinic in the future.
35:46Next slide.
35:48Just highlights some of the work
35:50that Scott has done working with
35:52the Copper Group to look at at
35:55outcomes in patients with lymphoma.
35:57And so Scott has done a number
36:00of studies including these two,
36:01one of which shows that patients
36:03with who are older than 80 have a
36:06higher frequency of discontinuing
36:08active therapies like a brute,
36:10not within the first 180 days.
36:12So obviously one has to go back and look
36:16at why that is and ways that we can.
36:19Alter that therapy so those patients
36:21can continue to be treated and then
36:23also Scott has done a lot of work
36:26with cost effectiveness and this
36:27is just one of his studies looking
36:30at different treatments for CLL.
36:31Getting a brute nip upfront
36:33versus getting it later on.
36:34So again,
36:35Scott has presented some of this
36:37work at the national meetings.
36:39Then there are a number of
36:41studies ongoing with copper.
36:43Next slide will then segue us into T cell.
36:46Lymphoma is T cell lymphoma.
36:48Is overall are heterogeneous as
36:50arviso bomas and tend not to do as
36:53well with conventional therapies as
36:55you can see in the outcomes curve
36:58progression free survival in median
37:00survival is poor for many of these.
37:03Aggressive T cell subtypes.
37:05The next slide.
37:07Highlights one of the things that
37:09we've been trying to do so patients
37:11with T cell lymphoma get chop based
37:13chemotherapy upfront and only a small
37:15percentage of them actually are cured.
37:17With this approach,
37:18patients would go on to an
37:20autologous stem cell transplant if
37:22they have a complete remission,
37:24but it turns out that when
37:26you look at registry studies,
37:27one of which we conducted here,
37:29only about 25% of patients
37:31upfront ever make a transplant.
37:33The reason being that many of those
37:36patients don't have a good remission.
37:38And so this is a study that I worked
37:40on with tar Sheen and this study
37:43is hopefully going to get started
37:45very soon where we combined Mogamu
37:48Lizum app with upfront chemotherapy.
37:50In this case, epoch for patients
37:52with aggressive T cell lymphoma.
37:54The idea being that Mogamulizumab is
37:56a CCR four monoclonal antibody that
37:58targets both tumor cells at but also more
38:01importantly T regs in the micro environment,
38:04so we're hoping that there's
38:06going to be an interaction.
38:08Both in the micro environment as well as
38:10potential synergy with the tumor cells.
38:12When this is combined with chemotherapy,
38:13I don't have a slide to show you this, but,
38:17uh, she has also developed some very nice
38:20correlative studies to go along with this.
38:22The next slide.
38:25Will take you into the world of relapsed
38:27T cell lymphoma and just to demonstrate
38:29to you the work of our group to look at
38:33a number of different agents targeting
38:34a number of different pathways that
38:36are relevant and some of these studies.
38:38Yale has been the top one or or two
38:41in terms of accrual for these studies
38:43nationwide and these are novel
38:45agents and I'll touch on a couple of
38:47them in the next slide or two.
38:50Um, go back and this is this is next slide.
38:57OK,
38:57this is tipifarnib which is a
39:00farnesyltransferase inhibitor,
39:00but it turns out that that it also
39:03down regulates CX CL 12 which is
39:06in the micro environment patients
39:08who have expression of CX CL 12 in
39:10the micro environment don't do as
39:12well as you can see on this survival
39:15curve and we've had some incredibly
39:17dramatic responses using this single
39:19oral agent and some of our patients
39:21such as this gentleman who has failed
39:24multiple therapies in autologous
39:25transplant that this is really salvage.
39:28A lot of people were hoping to
39:30initiate some Iits with this molecule
39:32in the next couple of months.
39:34Next slide shows you another
39:36approach with micro RNA,
39:37so this is the first in man study
39:39of this micro RNA which targets a
39:41number of different types of lymphoma.
39:44We put a number of patients with
39:46cutaneous lymphoma on this trial and
39:48you could see responses in pretty much
39:51all of the patients that were treated
39:53based on these waterfall plots and
39:55on the next slide I think is really.
39:58One of the most important findings.
40:00This micro RNA,
40:01which is its activity in HTLV one
40:04associated adult T cell leukemia,
40:07and again we put the majority of
40:09patients in this cohort on this
40:12trial and we also initiated the
40:14correlative studies that you see below,
40:17showing that the molecule directly
40:19inhibits the proliferation of ATL cells.
40:21Modulates the expression of various
40:24activation markers and you can see
40:27the changes in proliferation index
40:29with this molecule and this is.
40:31All samples from our patients that
40:33were drawn at different time points,
40:35so we're very excited to get this
40:38data published.
40:39Next slide. Just a couple
40:42of other studies initiated.
40:44This is another of Pershing
40:46study looking at incorporation of
40:48pembrolizumab with an active agent
40:50Brentuximab dowtin in CD 30 positive
40:52T cell lymphoma is and again this
40:54is this is her IIT and there are
40:57some correlative studies associated
40:59with this and the next slide.
41:04Yeah, the next slide will segue into
41:06some of the efforts that Francesca has
41:09looking at in a couple of different areas.
41:12In the context of aggressive lymphomas,
41:14this is her global T cell consortium study,
41:17which she conducted at Columbia
41:19and is now brought to Yale,
41:21and this is now a randomized phase
41:23two study where she's looking at 5:00
41:26or oral is incited gene in Rome and
41:29Epson compared to investigators choice.
41:31This is a multicenter study.
41:33And we're really excited that
41:35Francesca has brought this to us and
41:39the next slide is another effort in
41:41an area that we have not explored.
41:44Which is PTLD so post transplant
41:46lymphoproliferative disorders.
41:47In this study,
41:49Francesca is using sequential
41:51treatment for patients that are CD
41:5320 and CD 30 positive and you can
41:56see the scheme for this trial here.
41:59This is also an IIT that's being conducted
42:02in collaboration with the Mayo Clinic.
42:04Would you be a?
42:05So I think we have some really nice work
42:08from some of our younger investigators
42:10and we're very excited about that.
42:12The next slide.
42:14Is just our summary slide looking at what
42:17our future is and where we're hoping
42:19to go in the lymphoid malignancy's.
42:22So clearly we will benefit from
42:24the annotated database that you've
42:26heard about and hopefully will be
42:28contributing our samples in an
42:30ongoing fashion to the biobank.
42:32We also need to develop a sequencing
42:34platform which we really don't
42:36have here at the institution.
42:38For lymphoma we're currently
42:39sending our samples out,
42:41but we certainly would like to
42:43do that in the near future.
42:46I talked about the biobank and
42:47how important that is,
42:49but also we're now starting to talk about
42:51thematic direction for the program,
42:53and one of the areas that we're
42:55focusing on at least in T cell lymphoma,
42:58as you've seen,
42:59is on the micro environment,
43:01and you know immunomodulatory strategies
43:02that can be used with correlative science
43:04in these two cell lymphoma studies,
43:07and then finally,
43:08I just want to acknowledge the
43:10translational science collaborators
43:11and this by no means is an
43:13exhaustive list of folks,
43:14but there have been a number of.
43:17Studies that have been funded by both DeLuca
43:19as well as other mechanisms for funding,
43:22and those include studies done with
43:24the Cats lab with Marcus is lab,
43:27which is now being engaged
43:29with these studies.
43:30The Lola slab in pharmacology and
43:32even the imaging labs with a nuclear
43:35medicine with Doctor Chi and others
43:37that I didn't mention as well.
43:39So I think we have a very bright future
43:42ahead of us in the lymphoid malignancies.
43:45Thank you,
43:46Stephanie.
43:48Thank you for I've jumped.
43:50Thank you for seeing that is after
43:52you tour Tour de force and lymphoma
43:54is so excited about everything that
43:56is to come and very excited about
43:58our next presentation by Doctor
44:00Natalia never eats a on multiple
44:02myeloma in commodities.
44:03Stephanie, thank you so much for the
44:05opportunity to let me present today
44:07and I would like to echo some of your
44:10comments and thank thank Charlie for his
44:12outstanding leadership at the Cancer Center.
44:14So today I'm happy to present on
44:15behalf of myeloma team with brief
44:17clinical and research updates.
44:19Here's our team myself. Terry Parker.
44:21Know far Bar and Sabrina.
44:22Browning as well as Elon Gorshin at Guilford.
44:26Next slide please.
44:27I'll start with brief Brecht
44:29background about the disease.
44:31As you all know,
44:32multiple myeloma is the clonal plasma cell
44:35neoplasm originating in the bone marrow.
44:38The diagnosis rests on the bone
44:40marrow biopsy and some of the key
44:43immunohistochemical stains and protein
44:45studies on the blood in the urine.
44:47The ETL pathogenesis of this
44:49disorder remains largely obscure.
44:51We know of certain associations,
44:53such as perhaps antigenic stimulation.
44:55Role of.
44:56Pathogenic microbes,
44:57lipid antigens and other associations
44:59such as metabolic syndromes,
45:01diabetes and such,
45:02but in large majority of patients we
45:05don't know the cause and much remains
45:08to be elucidated in this research.
45:11Next slide, please.
45:13So as you know,
45:14the diseases continuum and we know
45:16that myeloma every case is pre
45:18preceded by the precursor state
45:20called M Gus monoclonal gammopathy of
45:23undetermined significance and after
45:25years of its presence it progress
45:27is to the early phase myeloma,
45:29commonly referred to as small
45:31during or asymptomatic myeloma.
45:33But a full blown clinical disease
45:35which requires active therapy is
45:37the disease which leads to end organ
45:40damage in the form of high calcium,
45:42renal failure, anemia and bone lesions.
45:44And in the old days we would
45:47resort to plane X Rays.
45:48However,
45:49this has been largely replaced by
45:51advanced imaging modalities such as
45:53whole body MRI or Whole Body PET CT scans.
45:55Next please.
45:57So once diagnosed,
45:59the treatment pattern of multiple
46:01myeloma consists of initial
46:02induction therapy with usual 3 drug,
46:05or in 2021 you might choose a four
46:07drug regimen incorporating some of
46:09the monoclonal antibodies upfront,
46:11such as daratumumab inappropriate patients.
46:13This is then followed by high dose melphalan,
46:17an autologous stem cell rescue
46:19AKA auto transplant,
46:20and then this is subsequently
46:22followed by maintenance therapy,
46:23which is usually long term and
46:26mental progression of disease.
46:27So the.
46:28Treatment pattern resembles a
46:30marathon rather than the Sprint.
46:32As we continue maintenance for many years.
46:34For those patients who remain
46:36in remission next.
46:39And invariably, sooner or later,
46:41every patient experiences their relapse,
46:43and this is due to branching pattern of
46:46clonal evolution or push persistence
46:48of previous clones and at the time
46:51of relapse patients have to sequence
46:54through the available therapies,
46:56each of which then leads to shorter and
46:59shorter overall duration of response,
47:01eventually leading to dismal prognosis
47:03for many of their refractory patients.
47:06Next please. Fortunately,
47:08we've had number of drug approvals
47:11over the course of the past decade,
47:14which includes the novel proteasome
47:16inhibitors in the form of carfilzomib
47:19novel immunomodulatory agents,
47:21pomalidomide, and others.
47:22The biggest breakthroughs came in 2015,
47:25when we had several approvals,
47:27namely IgG monoclonal antibody targeting CD,
47:3038 receptor on the plasma cell daratumumab,
47:33as well as checkpoint inhibitor,
47:35targeting SLAM F7 or CS1 elotuzumab.
47:38Orally available Proteus inhibitor
47:40exacum Abe.
47:41We also had approval for histone
47:44deacetylase inhibitor PANOBINOSTAT
47:45which is orally available and more
47:48recently a drugs of completely different
47:50mechanism affection such as selinexor
47:53received approval by FDA in 2019.
47:56This is a selective nuclear export
47:59inhibitor promoting some of the
48:01tumor suppressor gene action and
48:03within the past year approval of
48:06another IgG monoclonal antibody.
48:08Against CD 38 is I took some up with
48:11slightly different mechanism of action,
48:13but very similar to daratumumab and
48:16more recently just summer of last year.
48:19First antibody drug conjugate
48:20got FDA approval.
48:21This is Bill on time Out method Odin
48:24targeting B cell maturation antigen
48:26which is currently approved for
48:28relapsed refractory multiple myeloma.
48:30Beyond four prior lines of therapy next.
48:34So despite these therapeutic advances,
48:36number of clinical challenges
48:38remain primarily the concerns about
48:40what to do for refractory myeloma.
48:42Are we able to,
48:44in the novel immunotherapy era,
48:46replaced the high dose melphalan by
48:48some of the novel strategies such as
48:50car T cell or other therapeutics?
48:53How best to continue the maintenance
48:55therapy for patients particularly
48:57high risk data genetic subsets?
48:59And we're far from understanding the
49:01disease biology and choosing this
49:03sequential therapy based on biology of
49:05disease and its selection of therapy.
49:07Any cases is random and this is
49:10a clinical challenge.
49:11Same is true for a llama.
49:13Lodosa is,
49:13as you know,
49:14about 10% of multiple myeloma
49:16patients will develop concurrent
49:18soft tissue deposition of the Lambda
49:19or Kappa light chains,
49:21and this is an unmet need in all of
49:23gammopathy world as these patients,
49:25the care is not well defined,
49:27so it remains to be established
49:29what is the optimal first line,
49:31second line and beyond therapy for
49:33patients with this next please.
49:35So while facing these challenging
49:37issues in clinic we tried to.
49:39Integrate our clinical expertise
49:40and incorporate some of the Noble
49:43research therapeutic strategies and
49:45continue to educate our patients
49:47as well as our trainees next.
49:52In terms of individual focus of
49:54clinical expertise, Terry Parker has
49:56an outstanding clinical expertise in
49:58a llama low doses having served as.
50:00National Pi and number of a alloy doses,
50:04trials as well As for
50:06relapsed refractory myeloma.
50:07Nofar nofar sparkles has been
50:09mostly on high dose melphalan.
50:11Autologous stem cell transplant for myeloma
50:13as well as cellular therapies in myeloma.
50:16Sabrina also has an excellent expertise
50:18in a llama low doses shoot the
50:20separate fellowship in amyloidosis
50:22at the Boston Medical Center.
50:24She also focuses on understanding
50:26the biology of some of the
50:29precursor States and my own.
50:31Clinical research has focused On's
50:33to understanding clonal heterogeneity
50:35and incorporating advanced imaging in
50:38this disease therapeutic assessment.
50:41So education is of course an integral
50:43component of our daily work.
50:45This is a group of current fellows
50:48rotating through myeloma clinics
50:49during this academic year,
50:51and many of them have been involved
50:53in research projects in myeloma.
50:55So, for instance,
50:56Weixin Lou has been working on
50:58myeloma Yale Database project.
51:00On looking at outcomes in patients
51:02treated with monoclonal antibodies,
51:04Talib Dasani has the bone disease in
51:06myeloma cohort and looking to develop
51:09quality improvement project started.
51:10Targeting this Eric Chang will be
51:13involved in this promise study,
51:15which is the screening and community
51:17outreach project for patients with
51:20gammopathy's and their families,
51:21and it has an important outreach project,
51:24and we're partnering with Dana Farber
51:27Doctor Ghobrial on this project.
51:29And finally,
51:30Rose Mirkin will be involved in
51:32the collaborative effort where we
51:34may study the antigenic targets of
51:37monoclonal antibodies of myeloma
51:39with the help of immunology. Lab of.
51:42Aaron rink next please.
51:46So our research consists
51:47of different missions.
51:48On one hand, we always try to enhance
51:51our clinical trial portfolio.
51:53We have ongoing trials,
51:54both investigator initiated as well as
51:57industry and collaborative group trials.
51:59In every space of this disease,
52:01including early stage,
52:02small during as well as newly diagnosed
52:05and late relapsed refractory patients.
52:07And we always try to develop additional
52:10therapeutic concepts for refractory myeloma.
52:12Andale Emily doses.
52:13On the other hand,
52:16we do have certain outcomes,
52:18research initiatives and this
52:20include both myeloma as well as Mgas
52:23database as well as bone disease.
52:25In myeloma collaboration with our
52:27copper team and finally on the
52:30research basic Science Research front,
52:32we've been trying to build teams
52:34to collaborate with researchers
52:36to study monoclonal antibodies.
52:38They're driving antigens and Additionally
52:40mean profiling to understand predictive
52:42biomarkers of disease response.
52:44And study extramedullary disease next please.
52:49So on the basic science research front,
52:51I think the.
52:53Stephanie Collins,
52:54Biobank project for hematology has
52:57been really instrumental in our program
52:59at North Haven Myeloma program.
53:01We've essentially biobank the bone
53:03marrow and peripheral blood on every
53:06single patient that we diagnosed
53:08with multiple myeloma or gammopathy,
53:10and we hope to build collaboration
53:13and with the help from David Shatz lab
53:16to develop ex vivo multiple myeloma
53:18mouse models where we can develop
53:21robust preclinical models using this.
53:24In addition,
53:25studying monoclonal antibodies
53:26and understanding the antigenic
53:29targets and what drives the disease
53:31in collaboration with Aaron Rings
53:33lab on clinical research front,
53:35we've had active clinical
53:38collaboration and couple of IIT's.
53:41Closely working with musculoskeletal
53:43radiology and in this and
53:45haimson ending lishouk,
53:46both have been instrumental as
53:48well as our pathology colleagues.
53:51Mean issue and sang and pen know.
53:54Farhan Sabrina have ongoing
53:55collaboration with an Habermann from
53:57lab laboratory medicine to understand
54:00immune profiling of patients to
54:02understand the biologic response in
54:04different subsets of myeloma patients
54:06treated with monoclonal antibodies
54:08in terms of outcomes research.
54:10We've had active collaboration
54:12with hematology copper team.
54:14With the leadership of Shammai,
54:16my and Scott Huntington,
54:18we have several ongoing projects,
54:20and one of them a recent one using
54:22flat iron database and one particular
54:25myeloma project examining patterns of care,
54:28especially in the context of kovid period.
54:31And Lastly,
54:32we've been trying to build this disease team,
54:35which we refer to myeloma bone
54:38disease program collaboration,
54:39under which we try to bring
54:42together different departments,
54:43including Endocrinology, Carlin, Sonia,
54:45as well as orthopedic and spine center,
54:47Dieter, Lindskog, and Louise called.
54:50And as I said,
54:51Talib Dosani has an ongoing outcomes
54:53project looking into bone disease in myeloma.
54:57So with that I will stop.
54:59I'm exciting to have such great
55:02collaborators and colleagues on the campus.
55:04And I will leave a couple of
55:06minutes for questions.
55:07Thank you so much.
55:09Awesome,
55:10alright, so I'll share my screen.
55:12Just people know we have
55:14hematology joins 2021.
55:15We have a Twitter handle
55:17so we'll try and use it,
55:20so I'm going to unshare so we can
55:23see everybody and let me pull up the
55:26chat to see if there are questions.
55:30Are there questions?
55:32Would anybody like to raise their
55:34hand and ask the question?
55:36If not, I can start with one and then
55:39maybe I'll ask Francine since I'm
55:41always a molecular person and I know
55:44that we have this phenomenal effort
55:46to get on this goal panel and whole
55:49exome sequencing tower patients.
55:50Do you think that that will
55:53fulfill your need?
55:54Or what do we need to do to improve on that?
55:58I think that's certainly a start.
56:00You know, as you know Stephanie,
56:02we see some of these.
56:04We are rare lymphoma patients for whom
56:06there's really no treatment algorithm
56:08and which is kind of picking out of
56:11a hat to try to figure out what to do
56:13in the error of precision medicine.
56:15I really think that we should be profiling
56:17these patients and sequencing them
56:19and rationally developing strategies,
56:20so we would love to be able
56:22to start doing that.
56:24I think the critical component of that is,
56:26you know, is being able to get hold
56:28of that issue when it's biopsied,
56:31and to get it to the right place
56:33as soon as possible.
56:35We're also very interested in
56:37looking at circulating tumor cells
56:39and whether that's a strategy that
56:41we could we could use as well.
56:43OK
56:44fantastic exciting.
56:45Are there any other questions?
56:49I don't see any in the chat.
56:54So one of the I'm sorry Charlie friends, you
56:57know, I guess I would ask and
56:59I think you each allude to it,
57:02but where do you think cell therapy is going?
57:05And obviously it's relevant to each
57:07of the domains being described.
57:08So where do you think five years from now
57:11will be with respect to cell therapies?
57:15Well, we talk
57:16a lot about that with respect
57:17to transplant that we were just
57:19talking out at BMT rounds today.
57:21About whether we'll be doing autologous
57:23transplants in the future or not.
57:25I think that that's kind
57:27of where we're heading.
57:28I just wanted to say that one of
57:30the things that yell is doing,
57:32by the way, is we are developing
57:34our own party and we didn't get
57:36a chance to talk about that.
57:37But Doctor Katz and colleagues
57:38have developed the RNA car strategy
57:40and we're working on that.
57:41I know he has a B cell construct
57:43as well as one vertice Oklahoma,
57:45so I think the whole car world
57:47is undergoing evolution as well.
57:48And hopefully we're going to be
57:49at the forefront of some of that.
57:55Don't there's a question from the
57:58audience will then from Doctor
58:01Chi with a new drug substitute
58:03of chemotherapy. In treatments.
58:06Also, with the new drug substitute
58:10chemotherapy treatment. From Doctor chi.
58:18Yeah, I mean, I think that's
58:20a question to everybody.
58:21Can we get rid of chemo?
58:23This toxic stuff?
58:26We are that we added Temple where
58:30we were able to to do that,
58:33like I acute firestick leukemias.
58:35I mean, that's that's a poster child, I know.
58:39But potentially yes, that can be.
58:41That can be the one of the goal we have.
58:46We should not basically forget that
58:48chemotherapy is AB side effects,
58:51but targeted therapies have side effects too,
58:54and so we should not.
58:56Situation where we are really,
58:59completely disparaging.
58:59Chemo too much as it's as some real
59:03basically benefits for for some of
59:06the patient and for chemotherapy
59:08as well As for cell therapy.
59:10I think we need to see the big picture
59:14and how we can sequence and combine
59:18these different modalities of treatment.
59:21Rather than being one again
59:23the again the other.
59:26Awesome, so I think we have
59:29reached 1:00 o'clock or one minute
59:31past 1:00 o'clock tomorrow.
59:33Francine Natalia thank you for the
59:35fantastic presentation, Charlie.
59:36Thank you for hosting us and
59:38thank you for everything on behalf
59:40of everybody in immortality.
59:42And thank you to everybody who's attending.
59:45Yeah, phenomenal work. I just
59:47think about in my tenure what's
59:49been going on in hematology.
59:51Yeah, it's really exciting.
59:53So congratulations to all the
59:56speakers and all the investigators
59:58and staff working on this. No. OK.