www.broadcastmed.com Open in urlscan Pro
2600:9000:223c:3200:10:acf6:d680:93a1  Public Scan

Form analysis
1 forms found in the DOM

/search

<form class="bcm-site-header-search margin-top-no margin-bottom" action="/search">
  <label class="access-hide" for="bcm-site-header-search-keyword"><span class="icon icon-lg">search</span></label>
  <input class="form-control" id="bcm-site-header-search-keyword" name="q" placeholder="Search" type="search">
  <button class="btn btn-transparent" type="submit"><span class="icon icon-lg">search</span></button>
  <input type="hidden" name="syndicationCategoryId" value="3C67C700-FE02-11E2-B2B1005056890D87">
</form>

Text Content

 * Virtual Production & Broadcasting
 * Provider-Focused Site Development
 * Direct-to-Provider Marketing
 * Work with Us

 * menu
 * 
 * Gastroenterology
 * Heart/Vascular
 * Neurology
 * OB/GYN
 * Oncology
 * Surgery
 * Orthopedics
 * MORE keyboard_arrow_down
   
   Dermatology
   
   Diabetes & Endocrinology
   
   Infectious Diseases
   
   Otolaryngology
   
   Pediatrics
   
   Pulmonology
   
   Urology

 * menu
 * person

 * Procedures
   
   Anterior Pelvic Floor Repair
   
   Cancer Care
   
   Durasphere transurethral
   
   Enterocele and rectocele repair
   
   Partial Nephrectomy
   
   Pelvic Floor Repair
   
   Penile Implant Surgery
   
   Penile Transplant
   
   Prostatectomy
   
   Robot-Assisted Partial Nephrectomy
   
   Robot-Assisted Prostatectomy
   
   Robot-Assisted Ureteral Reimplantation
   
   Titan OTR
   
   Treatment for Nocturnal Enuresis
   
   Ureteral Reimplantation
   
   Urinary Incontinence Surgery
   
   Varicocele Surgery
   
   Vasectomy Reversal
   
   Virtue Male Sling

 * Conditions
   
   Bladder Cancer
   
   Kidney Cancer
   
   Kidney Disease
   
   Kidney Stones
   
   Male Urinary Incontinence
   
   Nocturnal Enuresis
   
   Overactive Bladder
   
   Pelvic Mass
   
   Prostate Cancer
   
   Prosthetic Urology
   
   Stress Urinary Incontinence
   
   Testicular Cancer
   
   Trauma (Urology)
   
   Urinary Tract Disorders
   
   Vesicoureteral Reflux (VUR)

 * Courses


UROLOGY

search search
Volume 90%

Press shift question mark to access a list of keyboard shortcuts
Keyboard ShortcutsEnabledDisabled
Play/PauseSPACE
Increase Volume↑
Decrease Volume↓
Seek Forward→
Seek Backward←
Captions On/Offc
Fullscreen/Exit Fullscreenf
Mute/Unmutem
Seek %0-9
1x1.25x1.5x
Live
00:00
00:00
08:41






 


Chapters

Transcript

Video


USE OF MELPHALAN FLUFENAMIDE PLUS DEXAMETHASONE FOR MULTIPLE MYELOMA



Paul Richardson, MD, Dana-Farber Cancer Institute, discusses the background and
findings of his study on the use of melphalan flufenamide in combination with
dexamethasone for the treatment of patients with multiple myeloma (MM) who have
received at least 4 lines of therapy and whose disease is refractory to at least
1 proteasome inhibitor, 1 immunomodulatory agent, and 1 CD38-directed monoclonal
antibody.



pleasure to join you. And it's actually my privilege to present on behalf of my
colleagues are work with mel fluff in as we call it in combination with
dexamethasone and the treatment of relapse refractory myeloma. I think just by
way of introduction I want to share with you some slides if I may that I think
would help frame our conversation this morning. This first slide is simply a
description of how malfunction works. I think it's a way to think of it as as a
peptide drug. Contradict that leverage is what we call um you know pet today's
is and actually borrowed from a very dear friend of mine dr Peter Vorhees who's
a co investigator actually in our work here is that it's something of a trojan
horse. It basically dives into the myeloma cell and allows the calculator
payload to be released in a highly targeted fashion within the cell. And what's
really interesting is the fact that this hydrophobic Libya filic platform allows
the delivery of a hydra filic lipa phobic calculator warhead into the cell. And
this is an important piece of medicinal chemistry because obviously the bone
marrow in which myeloma loves to live is a highly fat filled environment and
that's a micro environment in which the delivery of a drug that slip a phobic is
challenging. That's why traditional male fill in has to be rapidly dose
escalated in order for it to do its work. This is very different and it has a
novel mechanism action where the calculator warhead is selectively delivered to
the do muscle rather like a trojan horse. But most importantly because of this
rapid hydrologists driving a concentration gradient and allowing the increased
diffusion of Balfe aloof and into the cell. It's almost like the trojan horse in
that the Greeks not only get in and start to make mayhem in the city as it were,
but they also open the gates and allow more Greeks in. So the analogy to the
trojan horse is really a lot more powerful than one might think. Now. Based on
that we have pre clinical data led my colleague, Dharmindo chau han, which
really shows both in animal models and in bench in vitro model systems, dramatic
activity for malfunction even in highly mouthful and resistance cell systems and
most importantly, it's able to overcome Melville and resistance very much
significantly lower concentrations than we see. For example, in the experiments
illustrated in the right of this slide, What's also not shown in this is that
we're able to overcome resistance to other drugs as well in similar systems such
as partisan MIB and that's an important point because the deployment of
malfunction first and foremost has been in the setting of novel agent treatment
failure and that's where we've seen some very encouraging results. Now, the
first study to share with is the Lance of hematology paper that we published, yo
12 M one, which we published actually just last year. And in this trial we were
able to establish a dose and schedule formal fluff in at 40 mg once a month. Now
the important thing is that we combined malfunction in this study with
dexamethasone. This was a large trial and it was in over 70 patients all told
and we established an important cholera bility profile but also showed
convincingly that the combination of malfunction index method zone was the
direction in which to go recognizing that all our patients were steroid
refractory. So the decks methadone wasn't quote unquote making the difference in
the absolute sense. But clearly the two drugs together were better than just the
one. Now in that context, the 28 day cycle was established. Side opinions were
the major issue. We saw a solid response rate, particularly the combination
group of 31 and progression free survival was encouraging in the combination
group as well. Safety summaries here. I think it's important to emphasize is the
side opinions dominated but other side effects were very uncommon. However, in
this trial we had a very sick patient population and the number of patients who
entered the trial, we had rapidly progressive disease. And in a number of these
we saw septic events and in that context two deaths were considered possibly
malfunction related. So after this trial we were very alert to the possibility
of infection as a problem with malfunction indexing methods own bring into the
horizon trial. Now before I get to that I did want to share an important and
reassuring signal from the one to um study which was long-term survival. This
was 21 months. So whilst we obviously were on the lookout for this infectious
signal, we at the same time recognized that for this large cohort of patients,
the median overall survival approached 21 months and then a relapse refractory
population. That's not only impressive, but it also if you have a major safety
issue, you wouldn't necessarily expect that. So based on that the male fluff
index methadone combination was taken forward in our relapse refractory trial
and this was recently published in the journal of clinical oncology. This was a
very large trial of 157 patients in multiple centers across both Europe and the
United States. And in that setting were able to demonstrate solid response rate.
The investigative based assessment was 29%. The Independent review committee
actually confirmed it at 30% and this was in the intent to treat population. If
we look at the triple class refractory patients were able to see their very
similar response rate and here is summarized the progression free and overall
survival data which were again in such a sick, vulnerable population,
encouraging with the median overall survival approaching a year and a median
progression free survival in excess of four months. What's important to note the
side effect profile was reassuring in this regard. We saw side opinions as the
dominant issue, but we did not see fatal treatment emergent adverse events that
were attributable to malfunction in any case. This I think was important being
that the case, the important other side effect we were on the lookout for was
myelodysplasia. At the time of this analysis, there was clearly one case
documented with underlying by the display stick genetic change. Prior to study
entry. When we looked back and interrogated the genetics of the bone marrow
sample from. Prior to study entry, Having said that this is a particular side
effect. We're on the lookout for which is Dzemal fortunately today, that seems
extremely uncommon and rare. But again, because this is a delivery of a very
potent calculator warhead, it's something we'll be keeping a very close eye on
going forward. What was very good in this trial was that we saw that those
patients with extra medullary disease after monoclonal antibody treatment
failure in the main actually did remarkably well. We saw a response rate and
bone related extra medullary disease of 25 and then the true softest you plasma
system as we saw a response rate of 22 and you may say, well how does that
compare While other treatment approaches do not achieve that kind of degree of
response. Generally speaking, for example, dara to mob given in the dark. Um
Ahmad naive population as a monotherapy has been recorded to demonstrate
response rates in E. M. D. Of 17%. So to see a response rate of between 22 25%
In patients with extra medullary disease that reflects dara to mob or other
monoclonal antibody failure is a very important signal in our view and worthy of
further study. Further studies are summarized here and the ocean study led by my
colleague Peter Sonefeld is comparing ralph lupin and dexter methadone to pommel
intermittent. Next method zone similarly, Enrico Ceo, my colleague is leading
the fabulous study combining male flew for not only with direct um Ahmad but
also with autism IB. This is the direct human map data and the results are very
encouraging. Similar. The bore testament. It will also look favorable with
enrollment. Ongoing future studies are now including all fluff and dara. Touma
mob indexing methods own compared to dara um Ahmad dexamethasone as a backbone
with crossover permitted to ensure equal poise. My colleague Marie v. Matias is
leading this trial. We're looking forward to results from that. So in conclusion
malfunction is the first and only peptide drug. Conjugate leveraging, amina pep.
Today's is to date and represents a truly novel mechanism action for patients
with relapsed refractory myeloma. Importantly in combination, we've seen
meaningful clinical efficacy and manageable safety in patients with heavily pre
treated advanced relapse refractory disease And in horizon the overall response
rate was approximately 30%. And in that context, the manageable safety profile,
we found reassuring ongoing trials include ocean, lighthouse and anchor. And
we're very hopeful that this then constitutes an important new treatment option
for our patients.

Related Presenters

Paul G. Richardson, MD

Medical Oncology



View Profile

Published By



Published

May 19, 2021

Share

AddThis Sharing Buttons
Share to FacebookFacebookShare to TwitterTwitterShare to LinkedInLinkedInShare
to EmailEmailShare to MoreAddThis


For more than 20 years, BroadcastMed has been innovating digital strategies for
healthcare organizations. The company was first in the world to broadcast live
surgeries on the internet using its ORLive solution which provides an intimate
look inside the operating room.

--------------------------------------------------------------------------------

Topics by Specialty

 * Cardiology
 * Dermatology
 * Diabetes & Endocrinology
 * Gastroenterology & GI Surgery
 * Infectious Diseases
 * Neurology & Neurosurgery
 * Obstetrics & Gynecology

 * Oncology
 * Orthopedics
 * Otolaryngology
 * Pediatrics
 * Pulmonology
 * Surgery
 * Urology

--------------------------------------------------------------------------------

Additional Links

 * Privacy Policy
 * Virtual Meeting & Procedural Broadcasting Solutions
 * Provider-Focused Site Development
 * Direct-to-Provider Marketing
 * About Us

© 2021 BroadcastMed All Rights Reserved.

 * 

 * close

 * Cancer
 * Cardiology
 * Gastroenterology
 * Neurology
 * OBGYN
 * Orthopedics
 * Pediatrics
 * Morechevron_right
   * chevron_leftBack
   * Dermatology
   * Diabetes & Endocrinology
   * Infectious Diseases
   * Otolaryngology
   * Pulmonology
   * Surgery
   * Urology
 * person
 * Privacy Policy
 * Virtual Meeting & Procedural Broadcasting Solutions
 * Provider-Focused Site Development
 * Direct-to-Provider Marketing
 * About Us

 * close
 * 

Cancer

Cardiology

Gastroenterology

Neurology

OBGYN

Orthopedics

Pediatrics

Dermatology

Diabetes & Endocrinology

Infectious Diseases

Otolaryngology

Pulmonology

Surgery

Urology

--------------------------------------------------------------------------------

person

--------------------------------------------------------------------------------

Privacy Policy

Virtual Meeting & Procedural Broadcasting Solutions

Provider-Focused Site Development

Direct-to-Provider Marketing

About Us

close


This site uses cookies
We use cookies to ensure you get the best experience we can offer. By using our
website you agree to our use of cookies