@dgermain21 Yeah more confused about the biological rationale for Len in GCB than advocating for Ven in next gen trials
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Sean Corcoran, MD PhD
819 posts
Sean Corcoran, MD PhD
@S_Corcoran
PSTP Medicine Intern at Cedars-Sinai. MD @bumedicine. PhD @Cambridge_Uni and @theNCI via @NIHOxCam. Cancer Biologist. This is not my LinkedIn.
Los Angeles شامل ہوئے Nisan 2010
5.3K فالونگ847 فالوورز
I’d say a few things about GCB DLBCL.
(1) It’s a mix of very favorable and very adverse risk disease. We have some emerging data further deciphering DZsig biology on a granular level. Keep an eye out! But if a trial of R-CHOP + X is enriched for bona fide favorable (true) GCB DLBCL, it’ll be next to impossible to improve on SOC.
(2) Even if BCL2 plays a major role in some (or even a lot of) GCB DLBCL pathogenesis, many things can also be true, including but not limited to:
(a) All tumor cells sensitive to BCL2i are already adequately (or maximally) treated by R-CHOP. In essence, no “additional tumor kill” might be accomplished by also inhibiting BCL2 in the setting of a given backbone regimen. The calculus might be different in different scenarios, such as VIPOR.
(b) BCL2i on-target/off-tumor effects are likely profound enough that TRAEs wipe out any additional anti-lymphoma activity Ven+R-CHOP brings over R-CHOP alone. That’s what played out in the Alliance trials in DHL and DEL. Toxicity trumped anti-tumor effects.
Sean Corcoran, MD PhD@S_Corcoran
Im also not sure why the rationale would be that GCB patients would benefit from lenalidomide rather than maybe BCL2 inhibition etc. There aren’t many IRF4 positive GCBs!
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Im also not sure why the rationale would be that GCB patients would benefit from lenalidomide rather than maybe BCL2 inhibition etc. There aren’t many IRF4 positive GCBs!
John P. Leonard, MD@JohnPLeonardMD
For frontMIND results DLBCL #lymphoma there seems to be a lot hanging on idea that Tafa Len has positive impact in GCB subtype & might be prioritized there - despite non-significant difference there in comparison to ABC where there was clear difference evident w/fewer pts #ASCO26
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Sean Corcoran, MD PhD ری ٹویٹ کیا
Revolution Medicines $RVMD starts shipping experimental pancreatic cancer drug, daraxonrasib.
“We don’t have a set number where we are going to cap it. We want to make sure everybody who needs daraxonrasib for pancreatic cancer will receive it. That’s just very, very important for us to do,” CEO Mark Goldsmith told me last night at our #ASCO26 event.
Story in post below.
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Maybe it’s because I have pretty much 0 outpatient experience, but why do we do Phase III trials in DLBCL where the first cycle isn’t R-CHOP? Every ABC DLBCL patient I’ve seen does R-CHOP inpatient cycle 1 and Pola-R-CHP for the remaining cycles outpatient due to reimbursement
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@GuiperiniMD Is there evidence for DA-EPOCH-R in EZB-MYC?
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Another target-option for non-GCB DLBCL.
If ESCALADE is positive, we will have 3 great options for this population.
I would favor ibtk or Pola, though.
We need options now for GCB DLBCL. For now, R-DA-EPOCH for IPI >2 and MYC-R?
Let the controversy begins!🔥🔥🔥
Ash Alizadeh, MD/PhD 🇺🇸@AshAlizadeh
@lymphomahub ABC dominated responses with higher Gr3/4 neutropenia and thrombocytopenia
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Sean Corcoran, MD PhD ری ٹویٹ کیا
The following might seem a bit pedantic but I think the semantic distinctions matter.
In regards to #ASCO2026 podium questions regarding FrontMIND vs POLARIX and the conundrum of choices these 2 regimens now put before, two curious observations are worth considering:
1. Discussants still seem to misuse the term “underpowered” when I think they might mean “alpha not allocated”. Several prominent statisticians have each confirmed that POLARIX indeed had plenty of power to assess a COO:therapy interaction, even if this assessment was not a primary or key 2ndary EP of the trial. This association has been reproduced in more than a dozen other studies including 3 other RCTs.
2. Discussants still seem to misuse the term “retrospective” when I think they might mean “integral” biomarker. POLARIX indeed intended to analyze COO by Rx interactions per protocol as an exploratory correlative endpoint. Receipts below:
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I assume Spencer Pratt will lose. But whoever is making his videos is clearly the winner of this campaign.
Clay Travis@ClayTravis
These Spencer Pratt videos by @dsonoiki are better than 99.9% of political consultant ads. He does it again.
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Sean Corcoran, MD PhD ری ٹویٹ کیا
Shrey spelling 32 words in 90 seconds to win the Spelling Bee is the new greatest athletic accomplishment of 2026. I don’t even know how he said the letters that fast. Got a “Holy Mackerel” out of
@minakimes
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Gonna have to update my BMT wards talk if I can’t complain about IHC anymore…
Ash Alizadeh, MD/PhD 🇺🇸@AshAlizadeh
I used to be a vocal skeptic of Hans and a key GEP fan, some say as an OG for GEP. I used to lament Hans IHC as the only tool available for my patients, when many trials used GEP instead. But I have been surprised by learning how IHC has dramatically improved over the last decade or so with availability of standardized antibody clones, use of auto strainers, and interpretation consistency. How was I convinced? We did a systematic meta-analysis of >2200 patients from 19 studies. We used the PRISMA diagnostic test accuracy framework for comparing Hans to GEP. library.ehaweb.org/eha/2026/eha-2… Remarkably, this analysis now clearly shows that Hans is consistently non-inferior to GEP across current modern studies at a 10% NI margin for Accuracy, Precision, and Specificity. This solid performance of Hans IHC is very much in line with current CAP benchmarks for diagnostic tests, and within the margins of NanoString GEP using FFPE vs original frozen GEP as the original elusive gold standard. Long live Hans as the best currently available SOC for COO across the globe.
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Sean Corcoran, MD PhD ری ٹویٹ کیا
A warning from the president of MIT:
“the nation’s research enterprise is shrinking. Scientific funding is drying up. And the funds Congress recently allocated for science are not actually flowing”
“At public and private universities across the country, high-impact science is being damaged and derailed. Speaking for my own institution, compared to this time last year, MIT has experienced a decline in campus research activity funded by federal awards of more than 20%.”
Matthew Herper@matthewherper
MIT president: Why so many optimistic scientists are losing heart statnews.com/2026/05/27/sci… via @statnews
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Makes you wonder if it’s a transcriptional effect (which I think was seen in Art’s paper - cell upregulates BCR when signaling is extinguished to try to save itself?) or if it’s related to changing physical interactions by BTK dependent on conformation/phosphorylation status
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link.springer.com/article/10.100…
In the first year of my PhD I did a few experiments that showed overnight treatment with BTKi increased cell surface BCR, but interestingly nothing ever came out in the CRISPR screens.
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POLA-R-ICE vs R-ICE in r/r LBCL
Adding pola to R-ICE missed its 1ary endpoint overall.
Subgroup winners: DLBCL, relapsed, bulky disease & ⬆️ LDH all showed meaningful OS benefit.
1ary refractory disease? Pola won't save it. Perhaps BsAb-chemo combos are the answer there? #EHA2026
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Sean Corcoran, MD PhD ری ٹویٹ کیا
In fair warning I usually wait for information a little harder than the thing that triggered today's concerns. see if you can spot that.
but it led me to some funding data based pondering, in my partial excuse.
NIH funding skips drugmonkey.wordpress.com/2026/05/26/nih…
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Sean Corcoran, MD PhD ری ٹویٹ کیا
This one is hard to see.
The NIH Early Independence Award, one of the most competitive grants in the country for young scientists, will not go forward in FY2026. NIH says this is due to “administrative changes to funding opportunity processing and delays in approvals.”
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@AbdulElSayed That's interesting. Because under Medicare people pay premiums, co-pays, and deductibles. A real medical doctor might know that.
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Medicare for All means no premium, no co-pay, no deductible. Doesn't matter if you get a job, lose a job, turn 26, turn 65, get married, get divorce — it is there for you.
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Sean Corcoran, MD PhD ری ٹویٹ کیا
Useful @MattBruenig chart which reminds that “bottom 10% of income” does not line up that well with intuitive concepts of “the poor” since there’s a ton of retirees in there.
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Sean Corcoran, MD PhD ری ٹویٹ کیا
The fact that our current HHS Secretary felt the need to send out a tweet strongly clarifying he does NOT support rapid & innovative vaccine development as a response to a global public health crisis says a lot about where we are as a society right now, and who is determining US health policy… 😩
Secretary Kennedy@SecKennedy
Don’t believe Internet fearmongers. @HHSGov defends public health AND supports medical freedom — period. HHS action … ❌ Does NOT pave the way for a new mRNA vaccine ❌ Does NOT provide Big Pharma with new, limitless protections from liability ❌ Does NOT allow for mandates of ANY kind ❌ Does NOT apply to any other medical products ❌ Does NOT apply to vaccines HHS action … ✅ Facilitates expanded access of favipiravir — and favipiravir ONLY — to treat hantavirus ✅ Allows individuals possibly exposed to Andes virus to access this drug ✅ Only covers VOLUNTARY administration and use — NO mandates ✅ Provides protection for a VERY LIMITED TIME, through July 18, 2026
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🫨🫨
OpenEvidence@EvidenceOpen
Until now, physicians using AI in clinic had to assemble the patient’s context themselves. Allergies, comorbidities, medications, prior procedures, copy-pasted in from the chart. Today we’re announcing a partnership with @CedarsSinai. OpenEvidence now works directly inside Epic, drawing on the patient’s full record and interpreting the medical literature through the lens of that specific patient. Cedars-Sinai is the first academic health system to deploy patient-aware clinical intelligence at enterprise scale. The clinician asks a complex question in natural language. The answer reflects both the best available evidence and the patient in front of them. Patient data is never stored after the clinical session or used for any other purpose.
ART