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

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

February 03, 2021

Yale Cancer Center Grand Rounds | February 2, 2021

Anne Chiang, MD, PhD, and Francesca Montanari, MD

ID
6157

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.