"Transformation and Quality: Building a Cancer Network" and "Post Transplant Lymphoproliferative Disorders"

Transcript

• 00:00Substituting today very happy to be here.
• 00:03So we have two talks today and I think
• 00:06it should be a very interesting hour.
• 00:10Our first talk will be by Anne Chang and
• 00:13actually ends very much in the news today.
• 00:16Congratulations.
• 00:17And so an is associate Professor of Medicine,
• 00:20medical oncology and Deputy Chief medical
• 00:22Officer and Chief Integration Officer
• 00:24Officer for Smile Cancer hospital.
• 00:26As of about 3 hours ago.
• 00:29She specializes in thoracic
• 00:31oncology with a background in
• 00:32translational research and metastases,
• 00:34and a clinical focus has been built
• 00:36has been to build an amazing small
• 00:38cell lung cancer program here with a
• 00:41comprehensive portfolio of clinical
• 00:42trials testing novel therapeutics.
• 00:44Her research interests focus on focus
• 00:46and development of clinical trials and
• 00:49translational studies to test novel
• 00:51agents and combinations with immune
• 00:53checkpoint inhibitors for both small
• 00:54cell and non small cell lung tumors.
• 00:58Over now nine years an she's helped
• 01:00to build our smiling network,
• 01:02which I think will hear about today
• 01:05and overseas operations quality
• 01:06efforts in clinical research,
• 01:08adult care centers.
• 01:09She's a particular focus in quality
• 01:11measurement and improvement and
• 01:12his work to achieve ASCO copy
• 01:15certification for the entire smell.
• 01:16Academic clinical practice
• 01:17of actually received.
• 01:18Actually, the Joe Simone Award,
• 01:20just recently in Q just passed away
• 01:23last week, but a big honor for Masco,
• 01:26so an it's a pleasure to have
• 01:28you here for our first talk.
• 01:30Transformation in quality building
• 01:32a cancer network,
• 01:34and.
• 01:35Thanks Roy, it's really a pleasure
• 01:37to be able to talk to you today
• 01:41and thanks for the invitation.
• 01:43I was trying to decide between
• 01:45lung cancer and the network,
• 01:47but because of the timing of the
• 01:50announcement this morning and I
• 01:52thought that it would be nice to
• 01:54highlight the work that has gone
• 01:57into building a cancer network.
• 01:59So that's what I'm focusing,
• 02:01but I did put in a couple
• 02:03of slides with my trials so.
• 02:06I suck that in.
• 02:08OK, so I'm sharing my screen my disclosures.
• 02:14And this is for four.
• 02:16If you recognize it,
• 02:17it's South Ferry terminal farmers
• 02:19market in San Francisco and it's amazing
• 02:21place because the quality of the food
• 02:23and the shops are really outstanding.
• 02:26I had the best Peach I've
• 02:28ever had in my life.
• 02:29The atmosphere is buzzing in
• 02:31the shops are full of colorful,
• 02:33beautiful produce as far as you
• 02:35can see and when I was here which
• 02:38was pre covid the last time it
• 02:41seemed to me that this was more
• 02:43than a farmers market where.
• 02:45Each farmer sets up their shop
• 02:48individually next to each other,
• 02:49but somehow there was a transformation
• 02:52of the individual stands into
• 02:54a different collective entity,
• 02:56real community,
• 02:56and so in the same way that in
• 03:00the same way I want to talk about
• 03:03cancer or cancer network today,
• 03:05there really has been a trend
• 03:07over the past 10 years of academic
• 03:10institutions or other entities buying
• 03:13up practices or putting up their names on.
• 03:16Affiliated practices,
• 03:17but what I wanted to focus on is
• 03:20how to how I think we've built
• 03:23a real transformative network,
• 03:24a community that is better than
• 03:27the individual units where cancer
• 03:29delivery is really somehow transformed.
• 03:32And so you know, this is,
• 03:34let's go to transformation theory too
• 03:37as a guiding principle for this work.
• 03:39As it is,
• 03:41Carter said transformation is a process,
• 03:43not an event.
• 03:44And you start with a sense of
• 03:47urgency form a coalition and you
• 03:49create and share that vision.
• 03:51You empower others to act on that vision.
• 03:55You plan, create short term wins,
• 03:57consolidate those advances,
• 03:58and hardwire new systems.
• 04:00And I think the bottom line.
• 04:02Here is that quality improvement
• 04:05methodology is really been the basis
• 04:08of my job in the network and formed
• 04:10the foundation of building our vision
• 04:13over the past almost 10 years.
• 04:15So the objectives for today's talk
• 04:18really are two number one provider,
• 04:21network development, overview,
• 04:22describe quality concepts and
• 04:24metrics and network development
• 04:26to discuss ways to further the
• 04:28research mission in the network.
• 04:30And then finally recognize the
• 04:32benefits of expanded community.
• 04:34So this is how it all began.
• 04:38We we when I started my job this was in 2011.
• 04:43There was no network.
• 04:44We had hired anybody but we did have
• 04:47Yale Smilow state of the art disease based,
• 04:51patient centered clinical operation.
• 04:52We had outstanding faculty,
• 04:54staff,
• 04:54trainees,
• 04:55cutting edge clinical research
• 04:57resources and across organizational
• 04:59commitment for expansion and really
• 05:00a powerful coalition of folks
• 05:02to carry out that vision,
• 05:04which was really to provide
• 05:06comprehensive care to all patients.
• 05:08Close to home in Connecticut and to
• 05:11provide a platform for Yale Clinical
• 05:13Research and expand access to trials.
• 05:16So this is really the result.
• 05:199 1/2 years later the this.
• 05:21This is our clinical footprint in
• 05:24Connecticut and in Rhode Island.
• 05:26This stars are where our our care centers
• 05:29are and we do provide care to patients
• 05:33within 30 minutes of where they live.
• 05:36In Connecticut.
• 05:37We provide care to about 45% of
• 05:40newly diagnosed cancer patients in
• 05:43Connecticut and we also provide about or.
• 05:46We accrue about 25% of of therapeutic
• 05:49clinical trial enrollments as,
• 05:51as Roy mentioned,
• 05:53we have achieved ASCO quality
• 05:55oncology certification throughout our
• 05:57entire network in the main campus.
• 05:59This is away.
• 06:01This is actually the only way to
• 06:03certify ambulatory practices.
• 06:06Many of you are familiar with the AC OS,
• 06:10which certifies cancer programs.
• 06:13In all of the physicians are what YM?
• 06:18With the exception of Hartford,
• 06:21where the physicians are still
• 06:23Saint Francis employed,
• 06:24but do have a faculty appointments and
• 06:27are a stipend from from Yale and all
• 06:31of the staff are smilow employed or least,
• 06:35and we do have cross system policies
• 06:38and procedures and quality initiatives.
• 06:42This is a timeline where I started
• 06:44here in in in 2011 and and we did
• 06:47not have a network and then over
• 06:50the course of the next 9 1/2 years.
• 06:53We we brought in a practices and
• 06:56in in the in the.
• 06:59In doing so really had the opportunity to.
• 07:04Have multiple PDF a cycles in
• 07:06terms of improving our process and
• 07:09improving our in perfecting our
• 07:12onboarding process and now as I said
• 07:15we have 15 locations in two states.
• 07:17We have all we have almost 50 MD's,
• 07:2116 aips and over 400 staff we see
• 07:24over 9000 new patients 100 and
• 07:2625,000 treatment visits yearly and
• 07:29the contribution margin on an annual
• 07:32basis is greater than 110,000,000.
• 07:35So I think that this is really been
• 07:38successful and I'm going to talk a
• 07:41little bit about the onboarding practice
• 07:43the onboarding process first, so.
• 07:47This is where we really utilized
• 07:49integration and transformative change
• 07:51strategies to engage the stakeholders.
• 07:54The physicians that the staff
• 07:56in the practice, and we.
• 07:58There's at the bottom line is that
• 08:02there's really no shortcut here.
• 08:04It really is hard work having
• 08:07regular meetings on transition
• 08:09issues such as epic pharmacy,
• 08:11workflow changes,
• 08:12and those transitioned into practice
• 08:15meetings which were very useful.
• 08:18On an ongoing are useful on an ongoing basis.
• 08:22We developed a formal onboarding curriculum,
• 08:25and this utilized leaders and peers
• 08:27is faculty and it really included
• 08:30the Smilow vision and structure.
• 08:32Faculty roles and expectations.
• 08:34What does it mean now to be part of
• 08:38Yale and Smilow? How does quality work?
• 08:41How does the research apparatus work?
• 08:44Who are the dart leaders?
• 08:46What is that mean?
• 08:48What is what are academic mentors and and?
• 08:53So going through that that curriculum
• 08:56also involving team building
• 08:58and leadership training and
• 09:00including our multidisciplinary
• 09:01members not only met Aachen Heme,
• 09:04but our surgical colleagues are rat out
• 09:08colleagues pain and palliative care so.
• 09:12Um? Be the next.
• 09:16Either or the next part of quality
• 09:19improvement is really measurement,
• 09:21and this is a graphic of the really PDS.
• 09:24A cycle you have multiple.
• 09:28You know, iterations of
• 09:30how do you improve care,
• 09:32but measurement is really important,
• 09:34and so we started measuring at baseline
• 09:37because we wanted to make sure that we
• 09:40could measure progress and not just,
• 09:42you know, stick a sign on the door.
• 09:46That said, Yale Smilow and this paper
• 09:48published in 2018 really showed
• 09:50improvements in multiple domains of quality,
• 09:53including volume, clinical integration,
• 09:54quality metrics, and patient satisfaction.
• 09:57I'm going to show you. Few of those.
• 10:00At some of that data now.
• 10:03So in annual visits for chemo
• 10:05this you can see the main campus
• 10:08in blue over the years and then.
• 10:11When the Kirsten's Care Center
• 10:13started in in 2012,
• 10:15you could see the growth has really
• 10:17been significant and we do give
• 10:20now more chemo in our care centers
• 10:22closer to home for our patients
• 10:24than we do in the main campus.
• 10:28In terms of standardization,
• 10:30we utilized coping.
• 10:32Measurement Copy is a program through
• 10:35ASCO called quality Oncology Practice
• 10:39Initiative and it consists of.
• 10:41Go up to 90 metrics of of oncology
• 10:45of ambulatory oncology,
• 10:47quality that have been developed
• 10:49national iyanar consensus based
• 10:51and evidence based when available,
• 10:54so we had a measurement at baseline.
• 10:59Representing the practices before they
• 11:01joined and then this is four years
• 11:04later we looked at the significant
• 11:06differences and saw that really the
• 11:08only changes were in the positive.
• 11:10These are actually shown here and and
• 11:13so this was really important to me
• 11:16because I wanted to make sure again
• 11:18it wasn't just putting in a sign on the door,
• 11:22but that we were actually using.
• 11:26National consensus based metrics
• 11:28to show that we were improving
• 11:32quality for our patients.
• 11:34We also,
• 11:35as Roy mentioned at the beginning,
• 11:37did copy certification across our
• 11:39network and the academic campus.
• 11:41This is similar to the ACOs
• 11:44certification there.
• 11:4526 standards and you really have to
• 11:48show in document that the process
• 11:51from soup to nuts of chemotherapy
• 11:54administration and policies and
• 11:56procedures are in place that show us.
• 11:59That are up to snuff for ASCO
• 12:01certification and we re certified in 2019.
• 12:07Um, regarding clinical integration.
• 12:09I'll just show you the.
• 12:12And this represents cases
• 12:14President care Center cases
• 12:16presented at smilow tumor boards.
• 12:18We have 13 disease specific multi
• 12:20D tumor boards and we've asked all
• 12:23of our physicians to present one
• 12:26to two cases a month understanding
• 12:29that we can't present all of them.
• 12:32But really, those complex cases that
• 12:35need that multi D discussion needs to be
• 12:38presented and so you can see in 2013.
• 12:42This was difficult because the
• 12:44logistics around dialing in,
• 12:46which is so easy now by assume it.
• 12:50But at that time was very difficult.
• 12:52Getting the path reviewed, getting the.
• 12:56Radiology diagnostic imaging to be
• 12:58available that was really hard at the
• 13:02time and now I think we've received
• 13:04we've we've sort of the steady state,
• 13:07is right around 500.
• 13:09That's the case also.
• 13:10Sorry, this is 2018-2019, 2020,
• 13:12right around the 500 mark,
• 13:14which I think represents sort
• 13:18of the steady state.
• 13:20Um, with respect to customer service.
• 13:23Those of you who have.
• 13:26You know,
• 13:27pay attention to press ganey know that
• 13:30we always cluster in this 90s area.
• 13:33It's very difficult to make any changes here,
• 13:36but if you look at again baseline
• 13:38press ganey scores for practices that
• 13:41we acquired and six years later,
• 13:43you can see that in all of the
• 13:46cases we actually stayed the same.
• 13:48We're actually improved with one
• 13:50exception here is is this the site,
• 13:53but in some cases really significantly
• 13:55improved patient satisfaction.
• 13:59Um? This highlights some of
• 14:02the innovative projects that
• 14:04we've taken on in the network.
• 14:07This was a pilot with Asko Asko
• 14:09has a quality training program that
• 14:12is 6 months and has three didactic
• 14:15sessions and and a very aggressive
• 14:18curriculum every two weeks around
• 14:20process mapping and barrier analysis
• 14:22and and ultimately multiple PDS a cycles.
• 14:25In this case, we had a team from
• 14:29every care center at the time in 2000.
• 14:3217 and we did it again,
• 14:352018 which were interdisciplinary team.
• 14:38So we had doctors partnering
• 14:41with nurses or nutrition,
• 14:43or and in one case in MA Pharmacy
• 14:46to conduct quality improvement
• 14:48projects and all of those groups were
• 14:53able to complete at least one PDS,
• 14:56a cycle over two years or each year,
• 15:01each year getting through.
• 15:03Ipedia say cycle and this work
• 15:06ultimately resulted in nine story
• 15:09in five national presentations,
• 15:11and one of those projects that
• 15:15Jane Kanowitz lead in water Ferd
• 15:19in in 2018 is actually the care
• 15:23center quality goal for 2021.
• 15:27Um?
• 15:29I think many of the participants in
• 15:32these projects were really energized
• 15:34by the teams and the and what they
• 15:38learned around quality improvement.
• 15:40And one question was how
• 15:43do we sustain that gain?
• 15:45You know, I think that it's it's
• 15:48those it's important to be able to
• 15:51use those tools in Q I2 to better
• 15:54care and recognize opportunities to
• 15:57reuse them to face challenges and.
• 16:00And this is actually what we're
• 16:03doing now in the ambulatory
• 16:06transformation Work group we have.
• 16:08A number of groups that are
• 16:11really using the same Qi tools
• 16:13and change tools in lockstep.
• 16:15Action across multiple teams to
• 16:17respond to the pandemic and work
• 16:20towards transformation of care,
• 16:22whether it's relocation of sites
• 16:24or rapid uptake of Tele health.
• 16:27Or you know,
• 16:28developing and disseminating best practices.
• 16:30I think that this this this is the
• 16:34same process as the ASCO Smiler
• 16:36pilot but now applied to the.
• 16:39Immediate.
• 16:43Covid pandemic.
• 16:46Now that we're in, so you,
• 16:49I think you'll hear more about these.
• 16:52The work these groups are
• 16:54doing over the coming months,
• 16:57and I think it's been really exciting.
• 17:01So now I'm going to turn to clinical
• 17:04research, and as I mentioned before,
• 17:07we have about 25% of our YCC therapeutic
• 17:10enrollments from the care centers.
• 17:12This is also a process that
• 17:14needed to be built and hardwired.
• 17:17This is back in 2012.
• 17:19We had three cooperative group trials open
• 17:22and we had to figure out how to do ESO.
• 17:26Peas, around drug shipment and lab
• 17:28processing and training the staff and the.
• 17:31The docs to do trials where they
• 17:34hadn't done that before and as
• 17:36well as the Pisa trials to make
• 17:39sure that they were comfortable
• 17:41and had oversight of the process.
• 17:44Overtime we developed a monthly clinical
• 17:46research working group that has research
• 17:49champions from each site that meet
• 17:51monthly and vote on their portfolio.
• 17:53The disease team leaders come
• 17:55to those meetings and present
• 17:57their portfolio and new trials,
• 17:59and I think that this process is really.
• 18:03Grown obviously here in the next slide you
• 18:07can see that the accrual per the yearly
• 18:11accrual by sight and the highest sites.
• 18:14Saint Francis Northaven Trumbull,
• 18:16Fairfield.
• 18:17I think one of the things we've learned
• 18:21is that they need to have or they have
• 18:25a ACRSL lab which allows all protocols.
• 18:30No, let's which.
• 18:31Means that there's no limit on protocols that
• 18:36they can open due to lab processing times.
• 18:40Certainly the 2020 accrual
• 18:41was affected by Covid Inc.
• 18:44In our in 2018 we had 224 this year.
• 18:48If you take out the months that
• 18:50we had covid and we had very good
• 18:54accrual prior and and have really
• 18:57picked up now we would have certainly
• 19:00hit 200 between 200 and 220.
• 19:04If not for the for covid,
• 19:07so we activated a new site
• 19:09this year in Westerly.
• 19:11They are now treating some of the patients
• 19:15who were started in Waterford and.
• 19:19Now,
• 19:19in Rhode Island and you can
• 19:21see it actually in Waterford,
• 19:23which opened three years ago.
• 19:25There's been really great
• 19:27accrual growth there as well,
• 19:28so I think that there's really
• 19:31a lot of potential here if the
• 19:33next slide shows you the the
• 19:36yearly accrual by the DART.
• 19:37So which kinds of trials are are
• 19:40having the best accrual breast in
• 19:42GI have are certainly at the top.
• 19:47The long and heme are not far behind as
• 19:50well as T rad ngu that are increasing,
• 19:53so I think again, there's a tremendous
• 19:56potential here in the care centers,
• 19:58and as we have all.
• 20:00Our docs aligning with disease teams.
• 20:02I think this will just increase
• 20:06in the future. Um, this is the.
• 20:10I will quote Kurt Sabbath,
• 20:12who is one of our care center docs who
• 20:15helped to lead research initially.
• 20:18Now now hand it over to Neil Fishback.
• 20:22Kurt always said that he felt that clinical
• 20:24research is synonymous with quality,
• 20:27quality care because there's
• 20:28so many eyes on the patient.
• 20:30There's so much emphasis
• 20:32on important communication,
• 20:33shared decision making,
• 20:34and that really epitomizes quality.
• 20:36In our case,
• 20:37the vision had always been to
• 20:39to provide research as access
• 20:41to our patients close at home,
• 20:43and I think that even more
• 20:46than the numbers per site,
• 20:48this is what really strikes me.
• 20:50Every year we have somewhere around.
• 20:5285 to 87% of our physicians who put
• 20:55at least one patient onto trial.
• 20:58So I think we really changed that culture.
• 21:01We've had a research summit every year,
• 21:04usually around 80 people.
• 21:06That includes our care center docs or DART
• 21:09team members or CTO staff get prizes.
• 21:12We have about 13 care center
• 21:14physicians who served as PII on
• 21:17trials and right now we have 83
• 21:20trials open in nine disease types.
• 21:22About 50% cooperative group 43%
• 21:26industry sponsored in 10% IIT's.
• 21:31Here you see that our care
• 21:34center accruals form about 60%
• 21:36of our cooperative group trials,
• 21:38so that's really important.
• 21:42This is one of my trials.
• 21:44This is a national trial that we
• 21:47have opened in about guess 900
• 21:49sites across the US in Canada,
• 21:52but in our care centers as well.
• 21:54I'm National Co chair with has
• 21:57poor guy and it's a first line PDL
• 22:00positive trial for non squamous non
• 22:03small cell and I think that this is
• 22:06an important trial because it either
• 22:08randomizes you 2 two arms which
• 22:10start with immunotherapy and then
• 22:13if you progress you going to chemo.
• 22:15Or you add chemo to the pen
• 22:18bro Appan progression.
• 22:19That's an important question.
• 22:21This is the the chemo IO control arm and
• 22:25and this this trial I think will tell us.
• 22:28Very important.
• 22:31Give us information on sequencing of chemo.
• 22:34If you can spare it upfront.
• 22:36If you add it to the
• 22:38immunotherapy if that will help.
• 22:40And ultimately because we are
• 22:42collecting tissue from this trial,
• 22:44we're going to be looking for
• 22:46prognostic signatures for Pember Lizum
• 22:49app and predictive signatures for
• 22:51addition of chemo to immunotherapy.
• 22:53This is also an IIT of mine in small
• 22:57cell which with the biopsy upfront
• 22:59and then on treatment at week four
• 23:03after after treatment with EPI,
• 23:05Nevo and this trial has 17 patients
• 23:08who started on it with 10 paired pre
• 23:12and on treatment biopsies and this
• 23:15trial is open in our network and we've
• 23:18had 11 accruals from our network and
• 23:21I think that's important because.
• 23:24Talking to colleagues of bars
• 23:26across the country who have networks
• 23:29and who are trying to do.
• 23:32Clinical trials they've really relied
• 23:34on industry sponsored the cooperative,
• 23:36and very few actually have have
• 23:39diploid Iits in in the network.
• 23:42So this this just shows you a number
• 23:45of the items that we have and you can
• 23:49see that here's 12 accruals or 30% of
• 23:53Doctor Lacey's modified folfirinox,
• 23:55and in this case Doctor Kim Johans.
• 23:58That's 88% of her seven out of eight
• 24:02accruals for her and you know,
• 24:04for Doctor Nipper,
• 24:06it's a 4040% of her her accruals
• 24:09for her IIT as well so.
• 24:12I think this is really important research
• 24:16and support of our investigators at Yale.
• 24:21So what is the future hold?
• 24:23Among other things,
• 24:24I think there are certainly opportunities
• 24:27for building multidisciplinary care
• 24:29to enhance our Smiler signature of
• 24:32care in the network and to build
• 24:34on our current Med.
• 24:35Onken Hemang Craddock networks to
• 24:37support and our surgical oncology
• 24:39representation.
• 24:40We are developing formalized multi
• 24:42D clinics and that some of the work
• 24:45that I'm going to carry on in my
• 24:47integration role and strengthen
• 24:49our alignment with disease teams.
• 24:52And certainly our disease centers
• 24:54to provide service excellence
• 24:56and positive patient outcomes.
• 24:58This is my favorite slide.
• 25:00This is what I think is the most
• 25:03exciting piece of all of this
• 25:05is not not numbers of patients,
• 25:08but really I think the faculty that have
• 25:11joined his care center is one of them.
• 25:14Francesca is going to give a
• 25:16grand rounds right after me.
• 25:18They all master clinicians.
• 25:20They have devoted their really the
• 25:23clinical arm of a female cancer and
• 25:26smilow cancer hospital within the
• 25:28within the community and all have
• 25:31joined with the disease teams to
• 25:33do you know any number of really
• 25:37exciting things.
• 25:38BPI on trials do collaborative
• 25:40research projects, develop Qi projects,
• 25:42help teaching our house staff and
• 25:45anymore so it has really been my
• 25:48honor to represent these folks and
• 25:50to work with them. And I I can't.
• 25:55I can't emphasize enough that it's
• 25:58really been a work collaborative
• 26:00work of many, many,
• 26:02many hands to to build the network,
• 26:05including Charlie and Lori.
• 26:07Kevin Billingsley,
• 26:08Kim's lesser art flim, Aleesa Chomsky,
• 26:11Monica Fradkin, Connie Engelking,
• 26:12Roy Herbst,
• 26:13Stephanie Pauline, have invested so forth.
• 26:16Jeremy Court Manske will take over as the
• 26:20Chief Network Officer for Medical Services
• 26:23and head up the medication he Monk.
• 26:26And I will be focused on really developing
• 26:29the service lines and integration
• 26:31with our delivery care networks.
• 26:33So thank you for the time and.
• 26:37Think I. I'm done so I'd love to
• 26:40answer any questions if if there
• 26:42were any. Thanks and that was wonderful.
• 26:44And congratulations on a very well
• 26:46deserved promotion and we see why.
• 26:48So we have a few questions.
• 26:50Please put them in the chat.
• 26:52Melinda Erling comments were lucky to have
• 26:54this infrastructure with the care centers.
• 26:56I know a lot of non therapeutic
• 26:58interventional research being done in the
• 27:00care centers related to tobacco control,
• 27:01nutrition, exercise and obesity,
• 27:03so I will just follow up and say no.
• 27:07Make it secure.
• 27:08Diverse state as you go up
• 27:09and down the 95 corridor.
• 27:11How are we trying to help increase the
• 27:13diversity of our patient population at
• 27:14our care centers to get more patients
• 27:16from diverse backgrounds on trials?
• 27:18That's certainly something that
• 27:19we can now do that we have so
• 27:21much integration within the state.
• 27:25Great great great question.
• 27:26I'm just going to go back and share
• 27:29my screen again so you can see
• 27:31who's doing a lot of this work.
• 27:33You know, Melinda, that's a that's a
• 27:36planted question because we just put
• 27:39together a narrow one to study the
• 27:41lean interventions in the care centers,
• 27:44and I think that's going to be really
• 27:48exciting groups if you look here.
• 27:51This is Andrea Silver and she's
• 27:53done a lot of work actually devoted,
• 27:56you know, one of her passions is
• 27:59in in increasing under increasing
• 28:02representation of of of.
• 28:04In clinical trials and and
• 28:06addressing disparities of care,
• 28:08and she's done a number of things,
• 28:11including that grant the
• 28:13initial grant called own it,
• 28:15which was oncology works
• 28:17with New Haven getting.
• 28:20Community representatives to
• 28:21weigh in on what kind of research
• 28:24is done in the in at smilow and
• 28:27building those relationships.
• 28:28I think that you know our our latest
• 28:31cancer Grant has been incredibly.
• 28:35You know there's been a big focus on
• 28:38trying to increase representation of of
• 28:39of of folks in our in our clinical trials,
• 28:43and that certainly is a focus for us.
• 28:47Right, that's that wonderful one.
• 28:48More question.
• 28:49And then we'll move on.
• 28:50Someone comments. It's amazing
• 28:51how you built these tumor boards,
• 28:53even before anyone knew what zoom was.
• 28:55So now that we have zoom in,
• 28:58everyone can zoom from their
• 28:59phone from their walk.
• 29:00Can we use this technology to
• 29:02further integrate?
• 29:03You know multi modality,
• 29:04care subspecialty care with you
• 29:06showed us 55 or so doctors around the state.
• 29:08Are we using these tools of
• 29:10Tele Health to do even better
• 29:12now to integrate our care?
• 29:15Yeah, I mean, I think that with
• 29:18covid we've really we toggled up
• 29:20to over 50% of usage and adoption
• 29:23of telehealth during last spring.
• 29:25And and I think that we have.
• 29:28You know initiatives on next day
• 29:30access and improving access that
• 29:32we can utilize Tele health for,
• 29:35and certainly within our multi D clinics
• 29:37were thinking about doing that as well.
• 29:40I think there's a lot of innovation and
• 29:43you know I'll I'll mention you know again,
• 29:46Melinda's talked.
• 29:47I didn't talk about the non therapeutics,
• 29:50but we certainly have used the care
• 29:52centers as places to participate
• 29:54with the smoking cessation.
• 29:56Joe Biden Moon shot initiative.
• 29:58As well as.
• 30:00You know collect samples for Stephanie,
• 30:02Aliens, NDS,
• 30:03registry and and and and you know attempts
• 30:06to understand the science behind that.
• 30:08So I think there's just you know no
• 30:11end to what you can do with with the
• 30:14resources and the team that we have.
• 30:17Great well thanks Anne.
• 30:19Wonderful talking again,
• 30:20congratulations.
• 30:20So we have a second speaker,
• 30:23it's Doctor Francisca Montinari,
• 30:25Doctor Martner.
• 30:26Doctor Martin Ari is an assistant
• 30:28professor of clinical medicine in the
• 30:30hematology section and cares for patients
• 30:32with hematologic malignancies at our
• 30:34southernmost care center in Greenwich.
• 30:36Documentary recently joined Yell from
• 30:38the New York Presbyterian Hospital,
• 30:40Columbia University Medical Center,
• 30:42College of Physicians and Surgeons,
• 30:43which she was assistant Professor
• 30:45of medicine and Experimental
• 30:47Therapies Therapeutics in the
• 30:49Center for Lymphoid Malignancies.
• 30:51Doctor Montanari received her medical degree
• 30:53from the University of Pavia in Italy,
• 30:55which she graduated Magna ***
• 30:56laude and completed both residency
• 30:58and Fellowship and New York
• 30:59University School of Medicine,
• 31:00but she was awarded the Fellow
• 31:02of the Year Teaching Award.
• 31:04She served on the Institutional Review
• 31:06Board Committee and as director of
• 31:07the Institutional Lymphoma Tumor
• 31:09Board at Columbia University,
• 31:10and he is part of the steering committee
• 31:12of the Lymphoma Research Foundation,
• 31:14New York.
• 31:15Lymphoma rounds were so lucky to have
• 31:16been able to recruit Francisca recently,
• 31:19and she's going to talk to us now.
• 31:21About post transplant
• 31:23lymphoproliferative disorders franceska.
• 31:28Thank you for the introduction,
• 31:30so I'll share my screen.
• 31:38OK, so good afternoon everybody.
• 31:41I will review today was transparently
• 31:44proliferative disorders.
• 31:46So here's my disclosures. So we are.
• 31:50We will review together and how PLD
• 31:53are classified according to the
• 31:56most recent WHL classification,
• 31:59the Epidemiology, the risk factors
• 32:01at timing of onset prognosis,
• 32:04and therapeutic options including
• 32:06a current treatment paradigms,
• 32:08ongoing clinical trials and
• 32:11future directions.
• 32:13So let's start with the classification under
• 32:17the revised 2016 W 2 classification post.
• 32:21Transplant lymphoproliferative disorder
• 32:22are classified under the immune deficiency.
• 32:26Associated lymphoproliferative disorders,
• 32:28along with lymphoproliferative diseases
• 32:30associated with primary immune disorder,
• 32:33HIV infection and other
• 32:36iatrogenic immunodeficiency.
• 32:37Um, by definition they are any lymphoid
• 32:40or plasmacytic proliferation that develop
• 32:43as a consequence of immuno suppression.
• 32:45In order sequence of a solid
• 32:48organ or stem cell allograft,
• 32:50it is considered officiality.
• 32:52And based on the new classification,
• 32:55the device classification detailed
• 32:57include nondestructive PTL.
• 32:59These further subclassified
• 33:00into plasmacytic hyperplasia.
• 33:02Infectious modern closes like and
• 33:04Florida follicular pleasure which is
• 33:07a new entity under the new revision,
• 33:10polymorphic deity monomorphic TLD
• 33:12that comes into the B cell neoplasm
• 33:15and T cell nail Plaza and the
• 33:18classical Hodgkin lymphoma.
• 33:20So purely nondestructive,
• 33:22these diseases are classified based
• 33:24on the is the is the pathology major
• 33:28findings and undersell prevalence.
• 33:29There is usually preservation
• 33:31of the architecture,
• 33:33and these are polyclonal B cell
• 33:35proliferation by immunophenotyping
• 33:37genetic studies.
• 33:38There typically be positive the
• 33:40responsive to MENA suppression
• 33:43reduction in most of the cases and
• 33:45they are usually seen in kids.
• 33:48So in the pediatric population.
• 33:50So we do see on the bottom an example
• 33:53of plasmacytic hyperplasia with the
• 33:56preservation of the architecture
• 33:58of the lymph node and infiltrates
• 34:01of abundant plasma cells. Peter D.
• 34:04Polymorphic this is an entity that
• 34:07is characterized by either a genius
• 34:10mix of immunoblastic plasma cell
• 34:12and different size. The lymphocytes.
• 34:14The architectural is the architecture
• 34:17is usually faced.
• 34:18These are mostly polyclonal but
• 34:20presence of monoclonal B cell have
• 34:23been described and detected by
• 34:25immuno phenotype and genetic tool.
• 34:28There mostly EBV positive and
• 34:30some of them have been sealed.
• 34:33Six somatic hypermutation.
• 34:34So here's an example of
• 34:37architectural effacement on the left,
• 34:39with the associated to a large area
• 34:41of necrosis and on the right variable
• 34:44size and shape lymphoid infiltrate.
• 34:49Monomorphic PTSD, those are the one
• 34:51that do fulfill the criteria for non
• 34:54Hodgkin lymphoma or plasma cell neoplasm,
• 34:56small B cell lymphoma are not considered
• 34:59at not the designated as PTLT,
• 35:02with the exception of the beaded positive
• 35:05extranodal marginal zone lymphoma that
• 35:07usually arise in the cutaneous or
• 35:09subcutaneous tissue and this is because
• 35:12their standardized incidence ratio
• 35:13is not different than in the regular
• 35:16population and they're not started to happen.
• 35:19As a consequence of the immune suppression,
• 35:22besides those any other kind of non Hodgkin
• 35:25lymphoma is considered uppity ality.
• 35:27So the architecture defacement
• 35:29is usually present.
• 35:30Immuno, phenotypic and genetic features
• 35:32are typically recapitulating what we do
• 35:34see individual competent counterpart.
• 35:36And here I included an example
• 35:39on the left of.
• 35:42You should be selling for infiltrating.
• 35:45Lymph node and underwrite dereza.
• 35:47An example.
• 35:48This is a renal allograft biopsy with the
• 35:52showing about this planning T cell gamma,
• 35:56Delta,
• 35:56T cell lymphoma with the characteristic
• 36:00infiltration of the small blood vessels.
• 36:03Finally,
• 36:04classical Hodgkin lymphoma has
• 36:06also been associated and described
• 36:09in the setting of post transplant
• 36:11and is considered to be APTLD.
• 36:13It fulfills the criteria for the
• 36:15high school informing that we do
• 36:18see and immunocompetent population,
• 36:20but is typically mixed cellularity.
• 36:22It's always EBV positive and we
• 36:24do see that predominantly in the
• 36:27renal transplant recipients.
• 36:29Therapies treated like the Hodgkin
• 36:31lymphoma and immuno competent counterpart
• 36:34and here an example of a release time.
• 36:37Excel on the bottom surrounded
• 36:39by an inflammatory background of
• 36:41lymphocytes and using a fields.
• 36:44And this is our typical greatest number
• 36:47Excel with the city 20 CD 30 positive ITI.
• 36:50So very very Inter genius group of diseases.
• 36:53And so how?
• 36:55How frequently are our diesel informers?
• 36:58So we do about 40,000 transplant
• 37:00every year in the United States and
• 37:03period is the second most common
• 37:05malignancy in this patient population
• 37:08behind non Melanoma skin cancer.
• 37:10So it accounts for 21% of all the
• 37:13cancers in recipients of solid organ
• 37:16transplant as compared to only four
• 37:18to 5% of the cancers and immuno
• 37:21competent population.
• 37:22The incidence has increased over
• 37:24the past two decades and this is
• 37:27for a variety of reasons.
• 37:29The increased age at the older age
• 37:31of the Gilded Age of and owner and
• 37:35recipients new immunosuppressive treatment.
• 37:38The introduction of the haploidentical stem
• 37:41cell transplant and improved awareness
• 37:43of the disease and diagnostic schools.
• 37:46So after a solid organ transplant,
• 37:49the risk of developing a PLD
• 37:52varies for over 20% two point,
• 37:558% depending on the organ transplanted
• 37:57multi visceral intestinal being associated
• 38:00with a higher risk followed by lung,
• 38:03heart,
• 38:04liver,
• 38:04pancreas and with kidney being
• 38:06the carrying the lower risk for
• 38:09multiple attic stem cell transplant.
• 38:12The risks varies based on the
• 38:14HLA degree of the HLA matching.
• 38:17And the and the need for T cell depletion.
• 38:21So it is a highest for upload denticle
• 38:25without this addition 20% and it goes
• 38:28down to 3% in recipients of matched
• 38:31related dollar hematopoetic stem
• 38:32cell transplant. So what do we know
• 38:36in terms of risk factors besides
• 38:38the type of the transplant of the
• 38:41transplanted organ or the type of
• 38:44allogeneic stem cell transplant?
• 38:46For recipients of solid organ transplant,
• 38:48it is an established risk factor.
• 38:51The degree of Mr.
• 38:52EBV mismatch at the time of transplantation
• 38:54with the recipients being a big
• 38:57negative and the donor EBV positive.
• 39:00Also, the intensity of the induction,
• 39:03immunosuppression,
• 39:03treatment and duration of
• 39:05maintenance therapy,
• 39:05including increased the need of
• 39:07treatment due to graft rejection episodes.
• 39:10There is a strong evidence
• 39:12associated with the use of
• 39:13certain immunosuppressive drug.
• 39:18And in contact with others that
• 39:21are less associated and weak,
• 39:23evidence of risk is associated
• 39:26with infectious diseases and
• 39:28non EBV infection for instance,
• 39:31and other characteristics,
• 39:32genetic characteristics or
• 39:34underlying comorbidities of the host.
• 39:37For hematopoietic stem
• 39:38cell transplant recipient,
• 39:40age seems to be the biggest risk
• 39:43factor for development of these
• 39:46diseases and the conditioning.
• 39:48Regiment. Um also, um.
• 39:54So in terms of timing,
• 39:56typically PTSD arrives early in
• 39:58the setting of hematopoetic stem.
• 40:00The transplant and leader in the
• 40:03setting of a solid organ transplant,
• 40:06but it's not really that predictable.
• 40:08We considered an early onset if the
• 40:11PTSD arise in the first year after
• 40:14the transplant and the late onset,
• 40:17if it arises a year later.
• 40:19Starting one year after the transplant and.
• 40:24And the reason the battle,
• 40:26the pathogenesis is associated in the
• 40:29early onset to an acute EBV infection
• 40:32or a reactivation of the virus in
• 40:35the setting of a reduction of the
• 40:38MTV cytotoxic T cell lymphocytes,
• 40:40usually early PTLDREB positive,
• 40:41and frequently there is the
• 40:44allograft is involved.
• 40:45In the late onset there have been
• 40:49many hypothesis so hidden around
• 40:51the infection with the baby,
• 40:54then resolved and lymphoma keeps
• 40:57developing other viruses besides
• 40:59BV has been hypothesized as
• 41:01playing a role such as CMV,
• 41:04a persistent antigenic stimulation
• 41:06done by the allograft and lymphocyte
• 41:09deregulation in the setting of a
• 41:12chronic immuno suppressed state.
• 41:14These are usually.
• 41:16More likely,
• 41:17extra node with Extranodal involvement,
• 41:19not necessarily involving
• 41:21the graft and the monomorphic
• 41:24subtype is the most common.
• 41:27So what do we know about the prognosis
• 41:29of this disease that are regarding
• 41:32prognosis are mostly from single
• 41:34institution retrospective analysis and
• 41:36during my time at Columbia University
• 41:38I work on setting up a tumor bank
• 41:41for this disease with pathological
• 41:43specimen link to clinical information,
• 41:45and this is what we have learned
• 41:48from the analysis of 120 patients.
• 41:50This is the largest series published
• 41:52so far on this specific disease.
• 41:55Interestingly,
• 41:55most of the clinical.
• 41:57Features that we think might
• 41:59predict an outcome might have an
• 42:02impact on the overall survival.
• 42:04Did not correlate with overall
• 42:06survival in our patient population,
• 42:08including the subtype of the PTSD,
• 42:11the decade of diagnosis prior or after
• 42:14the introduction of their attack.
• 42:16Some organ do kind of organ transplanted
• 42:19DV status, graft involvement,
• 42:20and extranodal involvement
• 42:22or stage of diagnosis.
• 42:23So using a recursive partitioning model,
• 42:26we separated patient.
• 42:28Recursively,
• 42:29at each step into two distinct
• 42:31groups based on the variables that
• 42:33provided the maximal separation based
• 42:35on survival and using this model,
• 42:37we were able to identify based on
• 42:39age CD 20 expression and equal status
• 42:42for groups that were well separated
• 42:45in terms of roll survival and with
• 42:47an even number of patient and in the
• 42:50lowest group we can see that the
• 42:53medium overall survival was not reached.
• 42:55Those were essentially mostly pediatric
• 42:57patients with a good performance status.
• 42:59What is in the very high risk group
• 43:02elderly with a foot Burma status and
• 43:04essentially all patients with the
• 43:06CD? Twenty negative disease,
• 43:07the median overall survival was
• 43:09as short as one point 3 months.
• 43:11So what else we have learned,
• 43:14we know very well that T cell lymphoma
• 43:17have a much worse prognosis than Bissell
• 43:20informal immunocompetent population.
• 43:22But what are?
• 43:25What is the behavior of this LPT?
• 43:27LD is not well, no,
• 43:29not due to the rarity of these diseases.
• 43:32So we did analyze in our series of
• 43:34pulling over monomorphic PTSD and the
• 43:37differences between B cells and T cell TLD.
• 43:40And we do see that they sort of
• 43:42recapitulate what we do see and
• 43:44immuno competent counterpart in
• 43:46terms of prognosis with the median
• 43:48overall survival being very low
• 43:50for the T cell and compared to
• 43:53the diesel in monomorphic PLD.
• 43:55Also, we did observe that the time
• 43:57of the median time to answer it was
• 44:00much longer for T cell nine years
• 44:02compared to three years for the B
• 44:05cell type and all T cell period in
• 44:08our series were leaving negative.
• 44:11Another thing that that we we have
• 44:14also learned is that importance of more
• 44:17marrow of staging and the incidents
• 44:20of more involvement in the in PLD.
• 44:23It is very common in our series of
• 44:26patients at 23% of monomorphic PLD
• 44:29had bone marrow involvement compared
• 44:32in the in the T cell subtypes 50%.
• 44:35Also,
• 44:36polymorphic exhibited our very
• 44:37high bone marrow involvement.
• 44:3915.7 All the cases of polymorphic with
• 44:42where bone marrow involvement was detected.
• 44:46This resulted in up stage of the disease.
• 44:51And ever involvement was
• 44:52associated with poorer outcome.
• 44:54So we did compare the incidence of
• 44:57the involvement of Lombardy Boomer
• 44:59involvement in monomorphic PTSD compared
• 45:01to the normal diffuse large B cell
• 45:04lymphoma and HIV diffuse large B cell
• 45:06lymphoma patients diagnosed during
• 45:08the same time frame at our institution
• 45:11and we do see here that monomorphic,
• 45:14detailed involvement compared to
• 45:15the HIV positive diffuse large B
• 45:18cell involvement and this is suggest
• 45:20that that immuno compromised.
• 45:22State regardless of videology
• 45:24vial associated or higher trajanic
• 45:27maybe is a major risk factor for
• 45:31dissemination to the marrow.
• 45:32Finally,
• 45:33this is a loser.
• 45:36Analyze last year actually two years ago
• 45:38and this was presented at ASH in 2019.
• 45:40We did analyze the data regarding
• 45:42the cell of origin and the impact
• 45:45of treatment on the outcome of
• 45:47diffuse large B cell lymphoma.
• 45:49So these type and in our series
• 45:51non germinal center was more
• 45:53common than germinal center.
• 45:55I just want to highlight here that as
• 45:58previously reported and non germinal
• 46:00center PTSD is usually be positive
• 46:02versus germinal center is usually it will
• 46:05be negative clinical characteristic,
• 46:07organ transplant,
• 46:08immunosuppressive,
• 46:08treatment time of onset was not different
• 46:12in these two subtypes and there is a
• 46:14trend suggesting a better outcome,
• 46:16a better PFS and OS in patients with.
• 46:19Germinal standard compared to non
• 46:21germinal center mirroring the outcome
• 46:23in Indiana competent population
• 46:25and RE broker did not improve
• 46:27overall survival or progression.
• 46:28Free survival were compared
• 46:30to R chop but in not
• 46:32resulted also either in an increase
• 46:35toxicity in our series was
• 46:37extremely low and only one patient
• 46:39died in each treatment group.
• 46:43So the current challenges for PT LDR
• 46:45that this is an uncommon disease,
• 46:47as we saw there is a bigot originality
• 46:50in in the type of PTSD that is it
• 46:53originality in the patient population,
• 46:56in the allograft or multiply
• 46:58attic stem cell transplant,
• 46:59and immunosuppressive treatment they
• 47:01receive that is a high mortality rate
• 47:04that is associated with the chemotherapy
• 47:06and this is usually in length to
• 47:08the increased risk of infection
• 47:10that we do see in these patients.
• 47:13Population and unique to this patient
• 47:15population is the risk of graft failure.
• 47:18So currently general principle of treatment
• 47:23include immunosuppression reduction.
• 47:26I just want to mention that the
• 47:29only perspective trial that utilize
• 47:31immuno suppression reduction as part
• 47:33of a sequential treatment for this
• 47:36disease on a very large sample of
• 47:39you know on a very large number of
• 47:42patients 160 patient showed a 40%
• 47:45incidence of acute graft reaction.
• 47:47So typical in the adult population
• 47:50immunosuppression reduction
• 47:51is utilized at the same time.
• 47:53Other interventions such as
• 47:55rituximab are or combination.
• 47:56Chemotherapy surgery, radiation therapy.
• 47:58Unlikely.
• 47:59What we do see in Hodgkin and an
• 48:02article in former is a well established
• 48:06the treatment for stage one disease,
• 48:09PTSD and in the relapsed and
• 48:12refractory setting.
• 48:13There are adoptive immunotherapy
• 48:16utilizing EBV specific cytotoxic
• 48:18T cells and high dose chemotherapy
• 48:22with a toddler stem cell transplant
• 48:25or both being explored.
• 48:27So there are only few prospective trials,
• 48:31primarily on polymorphic and
• 48:33monomorphic beissel. PTSD and hold the.
• 48:37Stop for trials here.
• 48:39Um,
• 48:39use their attack some as a single
• 48:42agent with a very high with a good
• 48:45overall response rate under an CR rate,
• 48:48but not exciting overall survival
• 48:49due to early relapse is the best
• 48:52results that have been achieved
• 48:54that utilizing either a sequential
• 48:56treatment or a risk stratifies
• 48:58sequential treatment and this is the
• 49:00PTL D1 trials that is the largest
• 49:02phase two trial ever conducted
• 49:04in this patient population and
• 49:07reported by the German.
• 49:08Study group so will review
• 49:11the results of the PD L D1.
• 49:14The risk stratified sequential treatment.
• 49:17This was published in JCO in 2017.
• 49:21Patients were with that newly diagnosis
• 49:24of PTSD received an induction treatment
• 49:26with rituximab and then based on
• 49:28their response they received the
• 49:30consolidation with rituximab alone
• 49:32or they were escalated to our CHOP
• 49:35and 152 patients were enrolled again.
• 49:37This is the largest study in this
• 49:39disease that has ever been conducted
• 49:42and we do still at 1/4 of them
• 49:45after the initial induction with
• 49:47maximum achieved a CR and these were
• 49:50the patient that did not receive.
• 49:52Um,
• 49:53instead of toxic treatment,
• 49:55the overall response rate was a
• 49:58dieta CR rate 70%.
• 50:00Army generation of response was
• 50:02not reached and let me down.
• 50:04Overall survival was 6.6 years
• 50:06treatment related mortality in this
• 50:08study was 8% which is the lowest
• 50:11reported in this patient population and
• 50:13this is a attribute.
• 50:14This has been attributed to the
• 50:16fact that a quarter of the patients
• 50:19were spared cytotoxic chemotherapy.
• 50:21So. What's new in PID.
• 50:24Recently over the past five
• 50:26years it has been more and more
• 50:29recognized than PTSD tend to be.
• 50:32CD 30 positive So this is a study by vision.
• 50:36Others that showed that out of
• 50:38108 patients with PTSD diagnosed
• 50:40between 1994 and 2011, it was 85%.
• 50:43Of this patient expresses CD 30 including
• 50:4681% of the diffuse large B cell lymphoma.
• 50:50This is very particular to
• 50:52the query after the PTLD.
• 50:54Because in the immunocompetent,
• 50:56if you started selling for my
• 50:58usually city third expression is
• 51:00probably less than 20% and not only
• 51:03demonstrated a high CD 30 expression.
• 51:05They also demonstrated that it was
• 51:08associated with a better outcome. So.
• 51:11Twice this interesting or important,
• 51:14we now have a drug that targets
• 51:17specifically city 30 brentuximab windowed
• 51:19and is an antibody drug conjugate
• 51:22that binds to the city 30 and one.
• 51:26Since the internalised release,
• 51:27monumental restarting E which is
• 51:30microtubule disrupting agent which
• 51:32end up like causing apoptosis.
• 51:34As we all know,
• 51:35grant access method Odin is now
• 51:37approved with various indication in
• 51:40Hodgkin lymphoma anaplastic large.
• 51:42Calling from.
• 51:45So in 2019,
• 51:46at the ASH meeting,
• 51:48the results of these Phase 1 two
• 51:51trial of Brentuximab in Jordan plus
• 51:53rituximab as frontline treatment for
• 51:56patients with immuno suppression
• 51:58associated lymphoma were presented and
• 52:00in the this was a very small study.
• 52:0422 patients with previously untreated
• 52:07immunosuppression associated.
• 52:09Little pretty effective disorder,
• 52:10including 1516 patients were PTSD
• 52:12post transplant clipart affective
• 52:13disorder patients who receive
• 52:15an induction were attacks.
• 52:17In other words,
• 52:18given in combination with Brent
• 52:19accidents and Odin and patient worry
• 52:22stage and according to their response,
• 52:24they either received more out
• 52:26attacks immigrant tax map in loading
• 52:28as consolidation and maintenance,
• 52:29or if they had progression of
• 52:32disease were removed from the study.
• 52:35Again, small study,
• 52:36very short follow-up about
• 52:38encouraging result with a very
• 52:40high overall response rate,
• 52:41and see a rate of 60% so.
• 52:45I'm I'm very excited to announce
• 52:47that I that we're about to open a
• 52:50phase two trial for this patient
• 52:53population here in the Yale network,
• 52:55and this is going to be a trial
• 52:58in collaboration with them.
• 53:00Are you clinic and with UVI so is
• 53:021/2 is just trial where patients with
• 53:05post transplant lymphoproliferative
• 53:07disorder CD 20 and CD 30 positive
• 53:10which essentially is the vast
• 53:12majority of PTSD will receive
• 53:14an induction treatment with.
• 53:15Maximum burn toxin overload and
• 53:17and then based on the response
• 53:20at a pet city after induction,
• 53:22they will receive more of the same
• 53:24treatment so and there will be spared
• 53:27of cytotoxic treatment or will be
• 53:29escalated to rituximab, Pentax,
• 53:31Melvin Gordon, and Bendamustine,
• 53:33for a total of 6 cycles.
• 53:35Primary objective of the study.
• 53:37Our overall response rate complete
• 53:39and partial at the end of the
• 53:42treatment and PFS secondary objective.
• 53:44Intend to explore.
• 53:45Additional responsibilities at
• 53:47the end of the
• 53:48induction phase,
• 53:50which include the grant axiom of
• 53:52windowed in on top of rituximab,
• 53:55duration of response and overall survival,
• 53:57and we're planning to also deep dive
• 54:00into the frequency of infection.
• 54:02Peripheral sensory neuropathy,
• 54:04then rate doesn't craft of interaction
• 54:06and treatment related mortality.
• 54:08Exploratory studies.
• 54:10Are at the end to identify new biological
• 54:13and genetic markers that might be
• 54:15productive to response resistance
• 54:17to this therapeutic combination.
• 54:19So. Um?
• 54:23I'm going to leave you with this last slide,
• 54:26future strategies and these are.
• 54:28This is a list of the clinical trials
• 54:30that are currently about to recruit
• 54:32or recruiting for this for post
• 54:35transplant lymphoproliferative disorder.
• 54:37This top line is the study is our
• 54:40study that I just mentioned and
• 54:42we're about to open here at Yale
• 54:45and then the reason I just want to
• 54:48highlight the days a second study is.
• 54:53Study that follows up the PLD
• 54:56one trial from the German group,
• 54:58whether increasing where they're
• 55:00integrating the IPI score and the organ
• 55:03transplanted to further risk stratify
• 55:06patients after induction with rituximab
• 55:08and I have substituted rituximab
• 55:10subcu to the regular attacks enough
• 55:13that they used in the PTL D1 trial.
• 55:17Another trial that I would keep an
• 55:19eye on is there tax amount plus
• 55:22a club routine atrial that is not
• 55:24yet recruiting and is going to be
• 55:27done in Cleveland and besides this
• 55:29retrial which address the untreated
• 55:31population in the refractory setting,
• 55:32there are a lot of trials with
• 55:34the adoptive T cell treatment.
• 55:38And with this and this,
• 55:40is it? So thank you for your attention.
• 55:46Thank you, that was a wonderful
• 55:49talk and it's great to see that
• 55:51you have a trial and I guess
• 55:53it's opening Greninger will be.
• 55:55So very very well linked to the
• 55:57first talk we heard from Ann.
• 55:58Do you have any questions or comments
• 56:00where we're just about a time,
• 56:02but we might have time for one or two?
• 56:04If there are any.
• 56:09Are you seeing a lot of this
• 56:11in your practice right now?
• 56:13Princeska in Greenwich?
• 56:15Currently have one patient which is,
• 56:17which is a lot considering that
• 56:19I've just started two months ago.
• 56:21So we have we typically used to have.
• 56:25Colombia is a big transplant
• 56:27center and we we tend to.
• 56:29We were we were seeing a lot of
• 56:32these patients, but to say a lot
• 56:36was about 20-30 cases per year.
• 56:38Just to put this in context, so this is
• 56:41a rare disease weapon.
• 56:43As we grow Greenwich as a expert site,
• 56:45you know for these types of
• 56:47diseases you'll get you'll draw
• 56:49more and more from Manhattan,
• 56:50and where I'm sure there are
• 56:52many post transplant patients,
• 56:53Francine Flash has a question.
• 56:55She asks any role for checkpoint
• 56:57inhibitors in these EBV driven tumors.
• 57:00This is a very good good question and
• 57:03I think that due to the peculiarity
• 57:06of these patients population,
• 57:08which are recipients of hematopoietic
• 57:09stem cell transplant or solid organ
• 57:12transplant, there is a lot of.
• 57:16We're very worried about causing
• 57:18it'd have to be action or graft
• 57:21versus host disease, and so I don't.
• 57:24I'm not aware of any study
• 57:26utilizing checkpoint inhibitors in
• 57:29this specific patient population.
• 57:33OK, maybe I see a study in the making,
• 57:35maybe an investigator initiated trial.
• 57:38Well, our Francisco that was great.
• 57:40Thank you so much.
• 57:41Welcome to the group you've.
• 57:42It's great to have you and this
• 57:44will end grand rounds for today.
• 57:46I want to thank Renee and her team
• 57:48for helping get this set up and I hope
• 57:50everyone has a good rest of the day.
• 57:53Will see you see you soon.
• 57:56Thank you, thanks everyone.