Very excited to share our new study on determinants of resistance to anti-CD19 CAR T-cells (CART19) in large B-cell lymphomas (LBCLs)! Out today in
@Cancer_Cell
/1
I'm brokenhearted by the loss of my friend & colleague, Steve Coutre, a giant in
#hematology
. Steve trained & mentored me & inspired many to love & pursue
#hematology
. He touched the lives of many patients & peers as a clinician, scientist, & leader. My thoughts are w/ his family
Very excited to share our new study out today in
@JCO_ASCO
, deciphering the biological basis for the Diagnosis to Treatment Interval (DTI) in lymphoma and relationship to
#ctDNA
tumor burden.
#lymsm
Iโm broken-hearted and at a loss for words for our tragic loss of Sam Gambhir. He was not only a giant in the field, but also my friend, teacher, and role model. My deepest condolences to Aruna and Samโs family.
@StanfordMed
@StanfordCancer
@StanfordRad
@StanfordDeptMed
CONGRESS |
#PPLC21
| Jeremy S. Abramson
@MGHMedicine
discusses the future of ctDNA in NHL and how this tumor-derived genetic material has the potential (emphasis on potential) to aid in diagnosis, prognosis, MRD detection, and identification of targetable mutations
#lymsm
So excited to have my trainees presenting their work at
#ASH2019
in 7 orals and 2 posters. So proud of them for their unwavering energy, commitment, and passion for
#lymphoma
research!
@DrAEvens
Acknowledged indeed, esp given thousands of brave DLBCL pts & investigators who endured >20 yrs in more than a dozen trials, $billions spent, & famous Rx casualties along this path including Imbruvica, Revlimid, Velcade, Gazyva, Avastin, etc. Illustrated below (Kurtz/Alizadeh)
Dr. Max Diehn (
@max_diehn
) elected to the National Academy of Medicine for his work on liquid biopsies and precision medicine. This is one of the highest honors in the field of medicine. Diehn is the 4th current
@StanfordRadOnc
faculty in
@theNAMedicine
.
Now for
#LeonardList
key
#ASH21
#Lymphoma
abstract number 8 โ 709 โ Schroers-Martin โ Tumor-confirmed Follicular Lymphoma mutations detectable in blood years prior to clinical diagnosis
What an auspicious moment toward equity in science for a magnificent discovery that has shifted our paradigms. Congrats Dr Charpentier and Dr Doudna for this most well deserved recognition.
BREAKING NEWS:
The 2020
#NobelPrize
in Chemistry has been awarded to Emmanuelle Charpentier and Jennifer A. Doudna โfor the development of a method for genome editing.โ
Wasn't expecting primary CNS lymphoma in plenary
#ASH21
! Mutter et al.
PCNSL mutn in ctDNA in 78% cases (plasma) & 100% (CSF)
Could be developed into non-invasive diagnostic
Changes assoc with prognosis (PFS & OS) - could guide treatment decisions during Rx.
Impressive.
#lymsm
Yes, you can make immune organoids from primary follicular lymphomas AND test immunotherapies on them! Congrats to co-first authors
@Jkastens_phd
@schroersmartin
and couldn't have done this work without the incredible FL expertise of
@AshAlizadeh
New paper:
Most approved drug combinations for advanced cancer (1995-2020) have predictable clinical efficacy, because they have additive effect on Progression-Free Survival times.
In
@NatureCancer
at
by
@HaeunHwangbo
@SC_Patterson
@PlanaDeborah
1/6
Is it just me, or does it seem surreal to have an NIH Director (to rightly) advise ignoring CDC advice on testing? Doesnโt it seem a very slippery slope when public health guidelines are driven by politics instead of data and common sense?
1/13 โ Iโm excited to share that our study, โIntegrating genomic features for non-invasive early
#lungcancer
detectionโ was published today in
@Nature
. This has been my main project for ~4 years, and I am thrilled to finally share the fruits of my labor!
Scherer - ctDNA and PCNSL
- 67 pts 1ry or isolated 2ry CNSL
- CSF ctDNA PhaseSEQ nearly all pts, plasma in many
- preRx plasma ctDNA & tumour burden corr with outcome
- Pl ctDNA during Rx also prognostic
- CSF ctDNA v spec for diag
Really important work
#ASH21
#lymsm
Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM):
Wow. Honored to have two lightning bolts& elegance ascribed to
#PhasEDSeq
!! Excited to further demonstrate *impact* from key studies by
@ForesightDx
that will be presented soon!
Awesome work from Stefanie Meyer, Laura Pasqualucci, and team! targeting.
Unique and Shared Epigenetic Programs of the CREBBP and EP300 Acetyltransferases in Germinal Center B Cells Reveal Targetable Dependencies in Lymphoma
It's always a pleasure to sit on thesis committees of brilliant students who can invent, hack, and discover, doing so in applying engineering principles to biology and medicine. Congrats Dr Still &
@stanleyqilab
!
I learned the horrifying Sabatini news from a colleague, deeply concerned for their child's academic future, as a PhD student among the 39. We should stand united in providing ample support & refuge for such surviving trainees, to avoid their further trauma, & to learn from them.
Excited to share
#CIRI
, extending in-game win likelihood models to
#cancer
outcomes, using precision genomics & dynamic measures including
#ctDNA
#MRD
for diverse cancers! Looking forward to the possibilities for our patients.
In absence of prospective RCTs targeting CNS risk w agents like MTX, could we do better than murky retrospective data alone? Eg, what if baseline CSF
#ctDNA
predicts CNS relapse risk (in the absence of cytological evidence) & prospectively show that rx like MTX can eradicate it?
This is very nice and well-balanced summary by
@graham74GC
on role of CNS prophylaxis in DLBCL.
Iโll say that we wonโt ever have pros def data, so decisions (including changing practice) will be based on current best available โretroโ evidence.
@mattwilson2287
@AaronGoodman33
In recognition of his contributions to genome science, Howard Y. Chang of
@Stanford
is being inducted into the National Academy of Sciences. Watch the
#NAS159
livestream:
Congrats
@JakeChabon
&
@ForesightDx
team on this exciting effort to improve the lives of our patients using
#liquidbiopsy
. Excited to see what we can accomplish with sharper, more efficient, and more precise tools for
#MRD
.
@JohnPLeonardMD
Why replace imaging when the results complement? We learned how to fuse CT with PET, and we are now learning how to combine ctDNA with imaging. FWIW, there are now a lot more ctDNA data today than there were for metabolic imaging in lymphoma.
Fascinating that response to and benefit from Acala in 1L seems agnostic to COO and so rapidly discernible with
#ctDNA
. Excited to consider opportunities to personalize Rx based on such results!
Our PhasED-Seq
#ctDNA
liquid biopsy strongly correlates with standard of care CT imaging in
#DLBCL
patients and remarkably identifies treatment response to acalabrutinib in only 7 days.
Read the
#ASH21
abstract (524) here:
@AshAlizadeh
Thanks
@everettmoding
for this terrific synthesis! Hoping this review of
#liquidbiopsy
#ctdna
#MRD
& analysis of prior studies helps us pave a clearer path ahead toward better outcomes for our patients!
So wonderful to welcome
@NCIDirector
back to Stanford and join
@stanfordcbio
students for lunch! We really appreciate the wisdom you imparted, both at the talk and
@StanfordCancer
round table
#16ICML
David Kurtz and
@AshAlizadeh
group, PhasED Seq more sensitive and specific for MRD testing in DLBCL. Potential for MRD adapted and personalized approach to lymphoma therapy.
Together, our findings suggest a model of FL where BCL2 lesions are 1st, followed by accumulation of other mutations including CREBBP leading to clinical
#lymphoma
. Identifying the founding events of this cancer helps us identify important targets for
#FL
treatment. 10/12
Proud to share this labor of love by โฆ
@mohamshah
โฉ and team at โฆ
@StanfordMed
โฉ โฆ
@StanfordCancer
โฉ Functional significance of U2AF1 S34F mutations in lung adenocarcinomas | Nature Communications
@aadel_chaudhuri
What โivory towerโ are we really talking about? Academic physician scientists must sacrifice so much for the love of each part of the trifecta, that it seems slanderous to conflate the requisite probity of this calling with a privileged seclusion from โthe real worldโ.
#ctDNA
has great potential across cancers, yet its assessment in CNS lymphomas (CNSL) is more challenging because of low allelic levels, due to 1) lower tumor volumes and 2) decreased ctDNA shedding related to the blood-brain barrier. Does ctDNA still have value in CNSL?
Wow. Honored by the kind comments of
@KenLauLab
. Instead of continuing to think of cancers as isolated "islands", we look forward to connecting many more tumor biomes as "continents" linked to relevant clinical context using
#EcoTyper
@jeff_sharman
The genuine pursuit of the academic mission to advance knowledge, doing so as a core part of the job description, not as a bystander luxury or perk of the job.
When you mix complex immunology with Fox News politics, sadly you get Fox News politics. Glad to have
@SetteLab
@profshanecrotty
to the rescue, and to interpret their own data.
1/ There are various tweets misinterpreting COVID-19 โpre-existing immunityโ and making dangerous claims about herd immunity. Since many of those claims refer to our scientific papers, we will reiterate the facts.
@SetteLab
@ljiresearch
@ScienceMagazine
@CellCellPress
A beautiful synthesis of the state of FL risk & risk directed strategies by
@DrCarlaCasulo
. Would love opportunities to collaborate on ctDNA in FL as informing m7, POD24, tFL risk, and beyond.
Weโre pleased to announce the addition of Sandra Horning, MD to the Foresight Diagnostics Scientific Advisory Board. A seasoned clinician and biopharmaceutical executive, Dr Horning brings a keen interest in clinical MRD utilization.
#lymphoma
For example, this patient of mine discontinued therapy against medical advice for Stage IV DLBCL after only 1 rx cycle. This patient is nevertheless now alive without disease >6 years later, and was MRD-negative by PhasED-Seq just 25 days after start of therapy...
We set out to tackle this challenge by developing
#EcoTyper
(), a novel algorithmic framework for cell state & ecosystem discovery & validation from bulk, single-cell, and spatially resolved expression data. 4/
Welcome home! With the Soyuz hatch opened at 7:07am ET, the
@Space_Station
crew has doubled. Astronaut Kate Rubins and cosmonauts Sergey Ryzhikov and Sergey Kud-Sverchkov are now residents of our orbiting laboratory:
Interesting result. Beyond BL and T-ALL, I wonder if such MYC-driven NK deficits extend to MYC+ DLBCL and DHL, and if so, whether this could inform therapeutic strategies w CAR NK.
SCI member Dean Felsher and colleagues demonstrate a systemic reduction in natural killer (NK) cell numbers in mice bearing MYC-driven T-lymphomas. Targeting NK cells in future therapies may lead to effective treatment of these cancers.
@LabDfelsher
Thrilled and humbled to be the recipient of a 2021 ASCO YIA! Thanks to outstanding mentorship from
@AshAlizadeh
,
@max_diehn
,
@KiranKhush1
. Looking forward to digging deeper in early detection and lymphomagenesis!
@StanfordCancer
In
#DLBCL
, integrated profiling of >2.5k bulk tumors and >170k single cells by scRNA-Seq allowed us to discover & validate 44 cell states for 13 cell types, which together define 9 Lymphoma Ecotypes. 6/
How to accelerate
#SARSCoV2
evolution, a fairly slowly evolving virus, for the potential of functional mutations
1. Infection of immunocompromised hosts
2. Give convalescent plasma (without evidence) to hundreds of thousands of people w/ covid
3. Use ? effective vaccine regimens
Alterations in multiple classes of genes were associated with resistance, including B-cell identity (PAX5 and IRF8), immune checkpoints (CD274/PD-L1) and those impacting the microenvironment (TMEM30A). /7
@deniswirtz
visualizing heterogeneity within an individual tumor seems most valuable when that insight is generalized to other pts and many more tumors over space (and time). TMAs are a powerful tool for this, as is
#cfdna
#ctdna
. Can 3D TME methods be applied to thousands of tumors today?
@DrAEvens
@AaronGoodman33
@graham74GC
@Lymphoma_Doc
1st: begin by avoiding contaminating the literature w underpowered studies that claim RCHOP is sufficient for MYC+ and DHL/THL, when large studies have reproducibly shown otherwise.
@JohnPLeonardMD
Remarkably potent and an important advance for our patients. Yet these seemingly high CRS and ORR rates across Ph2 trials beg for some direct comparisons in future trials (when?) to give us a real sense of our choices in rrNHL
#lymsm
A fantastic collaboration from
@StanfordMed
and
@StanfordCancer
led by Brian Sworder, David Kurtz,
@StefanAlig
, and Matthew Frank with David Miklos &
@Max_Diehn
to help improve outcomes following CAR T-cell therapy in lymphomas & beyond /2