I am excited to share our manuscript "Therapeutic Implications of Detecting MAPK-Activating Alterations in Cutaneous and Unknown Primary #Melanomas" published at @CCR_AACR. I think it offers important clinical and translational insights into melanoma. 1/x

clincancerres.aacrjournals.org/content/early/… All of the genomic and clinical data are available on @cbioportal at cbioportal.org/study/summary?… – thank you to @nikolausschultz Lab, esp @chatila_w + @fjsanchezrivera (bioinformatics/data viz), Arshi Arora (stats), and @sloan_kettering molecular path (all the sequencing) 2/x

Hey everyone, the first-in-human clinical trial of tebentafusp, the HLA-specific fusion protein targeting gp100, is now online @CCR_AACR! Cool mechanistic proof of concept that you can get CD3+ cells into a poorly infiltrated tumor like #uveal #melanoma.

clincancerres.aacrjournals.org/cgi/content/ab… A prelim efficacy signal for uveal melanoma in this trial with a dose (50mcg weekly) that is lower than the 68mcg weekly dose later expanded upon and presented at ASCO last year. Fingers crossed for our patients with this rare disease!

(note: I have fCOI with @Immunocore)

Hi #medtwitter + new onc fellows! I treat patients with advanced #melanoma, especially rare ones like #uvealmelanoma (UM). This #tweetorial will discuss:

1) Why UM is unique
2) When does(n’t) immunotherapy work for UM
3) Why we prefer clinical trials for advanced UM

1/x UM affects about 5/million, and about 3-5% of advanced melanomas in the US arise from the uveal tract (iris, ciliary body, choroid). Of these, iris is rarest + least aggressive, so we often call it “choroidal” melanoma.

Get your dilated eye exams, folks!

2/x

Throughout our medical training, many of us were taught it was "unprofessional" to voice our beliefs or broadcast political opinions. But we must acknowledge most of the (well-meaning) people counseling us to stay silent stood to gain by maintaining the status quo. #medtwitter Those who maintain political activism harms the soul of medicine suggest it cripples the patient-doctor relationship. But I find this simplistic, even disingenuous. Surely most people can divorce political stance from compassionate care? Can't we trust them to make that decision?

A few thoughts on outpatient oncology care here in #NYC.

10 days ago, we melanoma med onc @sloan_kettering agreed to cut back in person clinic from 1-2x / week to once / 1-2 weeks. My clinic frequency was quartered. I was excited to leave the apt (I'm allergic to combs). My commute to work is entirely by foot, and I'm privileged to be able to do so. Ordinarily I walk by hundreds of people in 15 min.

Today, I counted about 30 people. We are successfully distancing! Yay!

Beautiful retrospective work suggesting the clone of melanoma that recurs after an initial complete response to checkpoint inhibitors is often different than the one that presented initially.

https://twitter.com/DrBetofMDPhD/status/1228072232641060865

Our group has taken these data to heart. I've changed a few things about my approach in clinic as a result:

1) When patients ask if we can just retry the same medicine if the disease comes back, I try to take time to say "yes, but it may not work the same way as before."

GITR + nivo efficacy ~ nivo efficacy.

Paper says, "...a clear signal has not emerged demonstrating that GITR agonism may be an effective therapeutic strategy in a broad patient population."

...yeah... OR maybe it doesn't add anything to PD-1.
jamanetwork.com/journals/jamao… Some of my best friends work on GITR!!! But that kind of language should have been edited out as Pollyanna nonsense. Don't make me sic Vinay Prasad on all y'all...

A huge THANK YOU to @CureMelanoma @MRFCureOM for giving me the Vision of Hope award this week. It's for, and from, patients with uveal melanoma and it means the world to me and my family. I have major imposter syndrome and feel like the only reason I was recognized is because I'm from a powerhouse place, @sloan_kettering. But I got the opportunity to thank lots of people and I'd like to shout them out again.

Vignette: young patient, Stage 4 #melanoma, complete response to nivo+ipi 2+ years. Pt is pumped, thankful. We hug it out.

We chat about good stuff. Marriage, kids, life plans. Big smiles. But there's a barely perceptible veneer underlying fragility. I know him well enough. I ask one of those classic M3-era open-ended questions. "How's life?" This sparks a longer, more ambivalent conversation. Grateful; yet scars persist:

- Pituitary issues
- weight gain despite replacement
- seeing therapist for PTSD from ICU stay
- forced into lesser paying job

Hey #tipsfornewdocs #medtwitter folks! I wanted to review side effects of immune checkpoint inhibitors (ICIs) for a non-#oncology audience. Immune-related adverse events (irAEs) present across all medicine specialties so we are all in this together. 1/x The most common ICIs are against PD-1 (e.g. nivolumab, pembrolizumab) and PD-L1 (e.g. atezolizumab, durvalumab). I use a blanket term “PD-1” throughout. Anti-CTLA-4 (ipilimumab) is a distant second; often in combo or directly after PD-1 in #melanoma #lung #kidney cancers. 2/x

Our retrospective look at tolerance and efficacy of BRAF-MEK inhibition post-progression on PD-1 for #melanoma is out! Mini-tweetorial to follow; some important questions raised. Thanks to collaborators like @amenzies9 @MGHCancerCenter @VUMChealth @MelanomaAus

https://twitter.com/JournalCancer/status/1070758581853675521

Phase 3 trials of BRAF-MEK inhibition:
Dabrafenib + Trametinib: COMBI-V (vs vem); BREAK-3 (vs dab mono)
thelancet.com/journals/lance…
nejm.org/doi/10.1056/NE…
Vemurafenib + Cobimetinib (coBRIM) thelancet.com/journals/lanon…
Encorafenib + Binimetinib: thelancet.com/journals/lanon…

I believe #DrChristineBlaseyFord and after catching up on today's #KavanaughHearing I realize I should have expected even less from a man nominated by our current administration. Of course he's going to have rage issues and get oddly vague and defensive about his drinking. And of course they won't pause for an investigation into serious allegations because the whole point is to "ram through" someone who mysteriously had up to $200k of personal debt mysteriously wiped away last year, not to hear and believe victim(s) of sexual assault.

My favorite patient benefit of this and ABC trials is simplifying the terrifying initial process for them.

Before: see Rad Onc. Get thin cut simulation MRI. 1-3 fractions. Start tx in between.

Now: see you in a week. Treatment can work everywhere. We'll keep a close eye on it.

https://twitter.com/NEJM/status/1032375659786465281

It bears repeating that patients were highly selected, couldn't be on steroids within ~7 days of start of screening, and had median largest met size of about 1.5cm. Most had only 1-2 target lesions (ie greater than 5mm). So please don't quote these ORRs to symptomatic pts.

1/ Some #melanoma posters and talks I'm excited to learn more about at @ASCO 2018:

#uveal 1 year OS 74% in @Immunocore Ph1b expansion of IMCgp100 (disclosure: I'm on ad board) meetinglibrary.asco.org/record/162309/… 2/ #uveal modest activity with BET inhibition as monotherapy

meetinglibrary.asco.org/record/158612/…
and
meetinglibrary.asco.org/record/160188/…

**100 emoji** Put another way, our job is to use what we know about that patient's health/personality/life circumstances, express the data in a relatable way, and give them room to express preferences that distinguish the choice.

https://twitter.com/medicalaxioms/status/994550420864319490

You can't ask a patient with advanced melanoma, "do you want nivo alone or nivo+ipi." Saying "using two drugs is more aggressive but has more side effects" is only marginally better. Doesn't give them the tools to choose wisely.

Reviewing records for clinic prep; for umpteenth time, outside CT printout (from pt's "mychart") doesn't include date of scan. #EMR design flaws abound; help me confess other #EMRsins @LeahJWitt @FutureDocs @RielyMD @adamcifu @DrMiguelPerales @jasonlukemd @OmidHamidMD #EMRsins when outside practitioners refuse to use dates and repeatedly copy forward references to "recently," "yesterday," and "soon."

Our @sloan_kettering #melanoma combo PD1+CTLA4 toxicity article now in print in @JAMAOnc - small N, but novel findings = delayed tox in ~10% of pts >16 weeks after stopping tx. Invisible to Ph3 trial reports. jamanetwork.com/journals/jamao… Changed my practice to check BMP, TSH, etc q3 months, even in NED patients, for first 12 months.

Important work in @JCO_ASCO by Keynote-001 investigators: complete responses maintained for 2yrs in most (but not all!) pts w/ #melanoma after elective d/c of pembro. ascopubs.org/doi/pdf/10.120… @JCO_ASCO Important clin features to remember as we extrapolate to routine practice: (1) these pts got CR without any local tx to residual dz; (2) among 67 pts who elected to stop, median CR seen at ~1yr; tx for median 7mo after first CR.