Wednesday, November 22, 2017

Sew Chaotically!! - African Wax Print top for a beautiful friend!!!

I had so much fun with my first foray into the use of African Wax Prints!!!

Here's the whole story:  Sew Chaotically! - African Wax Print Butterfly dress!!!
My dear friend, Ashia, has always been hugely and sweetly supportive of my sewing efforts!  But you should have seen her face light up in admiration of this fabric in particular!!  Despite my wild abandon in cutting out the pieces of my dress with zero focus on conservation of fabric....thinking only of which swath of color I wanted to place where...and the fullness of the dress itself..... I STILL had loads of fabric left.  6 yards is a lot, y'all!!!  So, I took it into my head to make a top for her.  I had her loan me a simple sleeveless, tunic top that she liked and fit her well.  I started with a basic paper tracing of front and back, with a line for the bust dart.  I don't know what I was thinking...something along the lines of:  just cut that line and slip in extra space....but quickly discovered what those with a brain more spatially related than mine would have intuitively grasped!  That WON'T work!!! was onto the internet to learn how to do a full bust adjustment!!!  (If you have looked at this blog for half a minute, you KNOW that is something for which I have had no prior need!!!!)  If you ARE in need, these two links were really helpful:

Workroom Social: Full bust adjustment tutorial

Craftsy: Full bust adjustment

It seems pretty clear and straightforward...NOW....but it pinched my brain for a minute there!!!

And there she is!!!  The top and my beautiful friend!!!  Love you, Ashia!!! - les

Monday, November 20, 2017

IMO-2125, a TLR agnoist combined with Yervoy (ipi) for folks with melanoma refractory to anti-PD-1

So, one of the MRF peeps put up a bit of an ad for this treatment...not entirely sure why, as that is not usually their role.  Perhaps they were just letting folks looking for a treatment option after failing anti-PD-1 know this trial was enrolling.  But, with so little intel out about this study and so many other options available - it piqued my interest.  It was quickly apparent that it is hard to find much info on it other than the super slick "presentations" made by the company who makes it, Idera, and the company who wants you to join their trial, MD Anderson, like these:

A Phase 1/2 trial of intratumoral (i.t.) IMO-2125 (IMO) in combination with checkpoint inhibitors (CPI) in PD-(L)1-refractory melanoma - out of MD Anderson

Idera Press Release for investors

But, when my intrepid medical researcher, partner in crime and all things got on the case, he found this:  Melanoma News Today - report from April 2017

It reads as follows:

Combining IMO-2125 and Yervoy Shows Promise in Certain Metastatic Melanoma Patients   By:  Daniela Semedo, Melanoma News Today, April 2017.

Combining {Idera's] intratumoral IMO-2125 treatment with Yervoy (ipilimumab) may be a promising treatment approach for patients with metastatic melanoma who are refractory to anti-PD-1 therapies, according to preliminary data from a Phase 1/2 clinical trial.
We are very pleased with the progress to date in the Phase 1 dose escalation trial of IMO-2125 in combination with ipilimumab, and with the outcomes observed,” Joanna Horobin, Idera’s chief medical officer, said in a press release. (Possibly the one I noted above.)

IMO-2125 in combination with ipilimumab demonstrated preliminary evidence of meaningful clinical activity in this anti-PD-1 refractory metastatic melanoma patient population which represents a high unmet medical need,” she said.
All dose levels have been well tolerated and did not exacerbate the safety issues commonly observed with ipilimumab,” Horobin said. “Furthermore, data from multiple parameters of immune markers from tumor biopsies have been very informative in establishing proof-of-mechanism and supporting the dose selection for the Phase 2 portion of the trial.”
IMO-2125, a toll-like receptor (TLR) agonist, is designed to activate cells from the innate immune system and induce the production of interferon — a potent activator of the immune system. Together, this is thought to lead to the infiltration of tumor-killing T-cells.
Because tumors have developed a method to impair T-cells from recognizing and attacking them, Idera believes that the drug could work in synergy with known and approved immune checkpoint inhibitors.
The open-label Phase 1/2 study (NCT02644967) was designed to assess the safety and preliminary effectiveness of intratumoral IMO-2125 in combination with the CTLA-4 inhibitor Yervoy or the PD-1 inhibitor Keytruda (pembrolizumab) in patients with metastatic melanoma who progressed after receiving anti-PD-1 therapies.  The study was set to be conducted in two parts: a dose-escalation portion (Phase 1) to evaluate safety and tolerability of multiple dose levels, and a Phase 2 expansion portion to assess efficacy.
While the Phase 1 dose escalation of IMO-2125 in combination with Keytruda is ongoing, the company has now announced that the Phase 1 part assessing IMO-2125 plus Yervoy has met the pre-specified futility assessment, meaning that the combination reached the established efficacy cut-off.
The company announced that all dose levels of IMO-2125 were well tolerated, and that the 8 mg dose level was established as the recommended Phase 2 dose.
Nine participants out of an expected 21 have enrolled in the Phase 2 portion of the trial assessing the objective response rate of IMO-2125 in combination with Yervoy. Data will be compared with historical controls treated with Yervoy alone.
Houston’s MD Anderson Cancer Center will continue to lead the study and will be joined by other clinical sites. Idera expects to have overall response rate (ORR) data early next year.
I am very encouraged by the tremendous progress that has been made to date to advance us to this important stage in IMO-2125’s development cycle,” said Vincent Milano, Idera’s CEO. “There is a very clear unmet medical need for those patients for whom current checkpoint inhibitor therapies are not providing adequate solutions.
We are incredibly focused on advancing this program as rapidly as possible for these patients, and we are also looking forward to exploring areas outside of melanoma in which intratumoral IMO-2125 may also serve an important role through its unique mechanism of action within the tumor microenvironment,” he said.
Idera also said it has started meeting with regulatory agencies about the best path to follow to register the combined treatment of IMO-2125 and Yervoy in patients with PD-1 refractory metastatic melanoma.
In addition, the company said the Phase 1 clinical trial evaluating the combined treatment of intratumoral IMO-2125 and Keytruda in PD-1 patients with refractory melanoma is enrolling as planned.  Moreover, a Phase 1 clinical trial evaluating intratumoral IMO-2125 alone (NCT03052205) in multiple tumor types should be enrolling the first patient in coming months.
Hmmm.....  Well, it is certainly a fact that we have folks who fail to gain effective control of their melanoma with anti-PD-1 and it's 40% response rate, leaving them in desperate need of an effective therapy!  It is also true that I encourage and fully support looking at any and all possible treatments to help them.  Yet, I remain a little puzzled here.  This statement sounds strong, but is substantially lacking in, hmmm....what's the word??????  " from multiple parameters of immune markers from tumor biopsies have been very informative in establishing proof-of-mechanism and supporting the dose selection for the Phase 2 portion of the trial.”  Oh!  I know what it is....DATA!!!!!!!!!!!!!!!  This report tells us NOTHING about how the folks in the phase 1 trial are doing!!!

An interesting aside:  The name TLR, toll-like receptor, came from the appearance the fruit fly larvae developed when used as subjects by researchers to isolate the molecule's function.  The larvae in whom the receptor was changed, looked very peculiar, or "droll", according to the German researchers who won a Nobel prize in medicine for this work.  And the German word for "droll" (i.e. funny) is "toll"!  The more you know....

While I hope IMO-2125 will absolutely be the cure for ever so many cancers, including melanoma, we need to remember that current intratumoral/intralesional therapies that are being combined with immunotherapy daily, to good effect, are available for melanoma patients in need and come WITH data supporting their efficacy!  Here's a post reviewing a wide variety of them and the DATA required for them to sally forth:

ASCO 2017: All things intralesional/intratumoral

If TLR agonists become the next great thing....will we all be cured of our melanoma AND have a great sense of humor...or just look a little funny?????  Hang tough ratties!  The road is long with lots of tolls!  And I mean LOTS!!! - c

Sunday, November 19, 2017

Back to the cooties in our guts....again!!!

We all want a magical cure for our melanoma!!  Short of that, we certainly want to do whatever we can to make sure the treatments we do utilize work to their very best effect!  In that vein, various studies have looked at the bacteria in our intestines, our 'microbiome' (or...the cooties in our gut!!), and how they may interact with immunotherapy.  Here is a prior post with links to several studies:

ASCO 2017: Melanoma, anti-PD1 and the microbes in your gut

Now there's this: 

Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Gopalakrishnan, Spencer, Nezi, et al.  Science. 2017 Nov 2. 

Pre-clinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-PD-1 immunotherapy (n=112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders (R) versus non-responders (NR). Analysis of patient fecal microbiome samples (n=43, 30R, 13NR) showed significantly higher alpha diversity and relative abundance of Ruminococcaceae bacteria in responding patients. Metagenomic studies revealed functional differences in gut bacteria in R including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and anti-tumor immunity in responding patients with a favorable gut microbiome, as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.

Best I can tell you is what I've said before ~ it is likely that our best bet is to avoid antibiotics unless really needed, eat kimchi, sauerkraut, yogurt and kefir!  Or.....fecal transplant, anyone???! 

Yum!!! - c

Thursday, November 16, 2017

Sew Chaotically! - Pinky Pink M6752 and "pattern" from J Crew RTW tank!!!

When Rosie was a little girl, she had an older brother whom she adored and Power Rangers were a thing!!!  However, she refused to accept the mantle of 'Pink Power Ranger' and held the Pink Barbie Power Ranger-esq character in great contempt!  So....Pinky Pink Power Woman was born!!!

A Pinky Pink Power Woman who was very proud of her eye the way!!!
Can you appreciate her fierce pinkness????
When I was in treatment with immunotherapy (nivolumab, now Opdivo) and incredibly painful (and utterly worthless) peptide vaccines...she made t-shirts for the Pink Peptide Posse!!!  [On the back of Ruthie's reads "TROUBLE" while the back of mine reads "DOUBLE!!!"  Does she know us or what???  And, yes, we did wear them together for some sessions!!!]  

Anyhow, though some think pink is a bit 'twee' for fashion, I love it. When I found this gossamer-like pink knit (fifth from the bottom above) in a shop in Walthamstow Market, London, I had to have it!!!  But, what in the world to do with such transparent, pink, delicate stuff????
Well, this.....
I had already used this pattern to make a cowl neck dress:  Here!  And got it into my head that I would make it into a top!!  But a top from fabric that flimpy [Yep! Flimpy is a thing!!!] and see-through...I would need an undershirt!  No worries, I could make that, too!
I've had this bias cut racer back tee from J Crew for years!
It fits me perfectly and I love it!!!  Plus, I liked the idea of the straps being slightly visible with the cowl neck top.  I should be able to use it as a pattern, right????
So....I did!!!  The shoulder straps came out a little thinner than I prefer, because the bias binding I made from the fabric was a little more cantankerous than anticipated!  I'll keep that in mind for my next one.
I really love it!
Now for the top!  Ta-dah!!!
I am Scott Boy Stoked about how this came together!!!

I had so much fun turning this simple idea into TWO garments I really like.  With trousers it is work ready.  With my city joggers, I feel ready for travel - to Italy - or the grocery.  With a pencil skirt it is dinner party perfect!  A Pinky Pink Power Woman outfit indeed!!!  (I hope the sweet, funny lady I met in Walthamstow while waiting to get our respective pieces cut [mine, this pink...hers a black terry] has made her "walking club" jacket!!!)  Wherever you are, whatever you're making ~ Sew, and LIVE, Pinky Pink Chaotically! - love, les
P.S. Thanks for being my Pinky Pink Power Woman Inspo, Roo!!!  I love you!!! - mommy

Wednesday, November 15, 2017

Circulating DNA - predicting survival in patients with resected Stage II/III melanoma

Wouldn't if be wonderful if a simple blood test could tell us if we have melanoma, what type of melanoma, and quantify the "amount" of melanoma...thereby giving us specific reports about whether our disease status is progressing, resolving, or stable?  Just think, with a test like that, we could quickly determine if we are responding to a particular therapy....or not!

I have posted data on this topic many times!  This link will take you to my last post and includes many more within:  ASCO 2017: Circulating DNA to measure response in melanoma

Now there's this:  

Circulating tumor DNA predicts survival in patients with resected high risk stage II/III melanoma. Lee, Gremel, Marshal, et al.  Ann Oncol. 2017 Nov 3.
Patients with high-risk stage II/III resected melanoma commonly develop distant metastases. At present, we cannot differentiate between patients who will recur or those who are cured by surgery. We investigated if circulating tumor DNA (ctDNA) can predict relapse and survival in patients with resected melanoma.
We performed droplet digital polymerase chain reaction to detect BRAF and NRAS mutations in plasma taken after surgery from 161 stage II/III high-risk melanoma patients enrolled in the AVAST-M adjuvant trial.

Mutant BRAF or NRAS ctDNA was detected (greater than/= to 1 copy of mutant ctDNA) in 15/132 (11%) BRAF mutant patient samples and 4/29 (14%) NRAS mutant patient samples. Patients with detectable ctDNA had a decreased disease-free interval and distant metastasis-free interval versus those with undetectable ctDNA. Detectable ctDNA remained a significant predictor after adjustment for performance status (PS) and disease stage. Five year overall survival (OS) rate for patients with detectable ctDNA was 33% versus 65% for those with undetectable ctDNA. OS was significantly worse for patients with detectable ctDNA and remained significant after adjustment for PS.

CtDNA predicts for relapse and survival in high-risk resected melanoma and could aid selection of patients for adjuvant therapy.

Soon!!  I hope, soon...this test (or something like it) will be refined and readily available for melanoma patients of all stages!!! - c

Sunday, November 12, 2017

Sew Chaotically! - The Basic InstincT t-shirt by Sasha!!!!!!!!!!!!!!

I have learned a great deal from many sewists through their blogs, tutorials, and other posts on various social media.  Some I simply watch, trying desperately to absorb all their tips and techniques.  Luckily, others have become peeps!!!  Amazing people...who touch my heart, make me laugh and teach me about life...not just sewing.  For a start there's Oonaballoona - aka Marcy Harriell who, via her blog, provided many tips for fabric shopping in NY, inspo and advice for the use of African Wax Prints, creates beautiful, personally authentic garments, and makes me laugh out loud!  There's Tilly, of Tilly and the Buttons, who inspired much of my London fabric shopping.  There's Rochelle, of Lucky Lucille who endlessly inspires me with her art, beautiful garments, work ethic and personal strength in not only enduring, but triumphing over personal challenges. I adore all the women who make up Mix and Sew.  French style is for real, y'all!!  I would be thrilled to be part of such a sewing group!  I adore their exuberance, willingness to admit flaws, and lovely sisterhood!

But, today -  I would like to introduce you to Sasha!!!  Her blog is Secondo Piano (that would be 'Second Floor' in Italian). I love her style, her passion!  Her dedication to authentic, sustainable fabric, fashion, and the way we look at garments, interpret, and make choices as "makers" inspires me daily!  If that is not enough, she MAKES great patterns!!!  AND....they are free!!!  Just subscribe to her amazing site!!!

Sew.....I happily embarked on making her Basic InstincT t-shirt!  To quote Sasha:
"I chose the relaxed cut because I think it’s a more contemporary silhouette and I personally do not like so much having my bra line showing. The crew neckline I just adore for its boyish, nonchalant look in a woman’s garment. I think it looks great under a blazer or a cardigan and can easily be lowered. I wanted this pattern to be a sort of I wanted this pattern to be a sort of blank canvas you could potentially transform into your own beautiful painting."

Great thanks to my B for printing and putting together another pattern.  (If you want, you can print only the size you prefer!  But, when you've got a helper willing to continually print and put together patterns for you...he can do it any way he wants!!!)

Here we go!

I used a drapey cotton knit from Mood I picked up a bit ago...

...and yes, one should make a muslin...but, I can't - be bothered!!!  I made the "small" with no changes, and luckily...the fit is fabulous!!!

I did ALMOST mess up my AMAZING t-shirt by being stubborn!!!  I was set on having my stripes go opposite to the body of the shirt on the neck band, and there was less stretch in that direction....but....I made it work!!!  

The Basic InstincT t-shirt  easily dresses up or down.  It plays well with skirts or pants, alone or with a jacket.  (Here I've added my Morris Blazer!) I can see this pattern becoming the wardrobe staple Sasha envisioned!  I am looking forward to other t's and dresses using this pattern!

Thanks, Sasha. And not just for this t-shirt!  Thanks for being you!!!  Sew chaotically! - les

Friday, November 10, 2017

Melanoma patients continuing Nivo after having adverse reactions to the ipi/nivo combo??? Yes, you can!

Though management can be tricky, docs have been saying from some time that folks CAN tolerate anti-PD-1 if you have previously had adverse reactions to ipi or a pre-existing autoimmune process.

Here's a report from ASCO 2016: Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders (AD) or major toxicity with ipilimumab (IPI).

And another post that includes several sources from this year:  Patients with preexisting immune disease, melanoma, and treatment with Anti-PD-1? Yes, this can be done. Yes, autoimmune flares should be treated with immunosuppressive therapy while on immunotherapy. And YES!!!! These patients can still attain a response!

Now there's this:

Safety of resuming anti-PD-1 in patients with immune-related adverse events (irAEs) during combined anti-CTLA-4 and anti-PD1 in metastatic melanoma. Pollack, Betof, Dearden, et al.  Ann Oncol. 2017 Oct 11.

Combined CTLA-4 and PD-1 blockade induces high rates of immune-related adverse events (irAEs). The safety of resuming anti-PD-1 in patients who discontinue combination therapy due to irAEs is not known.
We assessed patients who experienced clinically significant irAEs from combined CTLA-4 and PD-1 blockade leading to treatment discontinuation at four academic centers. We assessed the safety of resuming anti-PD-1 in terms of recurrent and distinct irAEs.

Eighty patients discontinued combination therapy due to irAEs, including colitis (41%), hepatitis (36%), and pneumonitis (4%). Of these, 96% received corticosteroids, and 21% received additional immunosuppression (e.g. infliximab). All were rechallenged with anti-PD-1, and 14 (18%) had recurrent irAEs at a median of 14 days after therapy resumption (6 grade 1-2, 7 grade 3-4, 1 grade 5 Stevens-Johnson Syndrome). Colitis was less likely to recur than other irAEs (6% vs. 28%). Clinically significant but distinct toxicities occurred in an additional 17 (21%) patients (11 grade 1-2, 6 grade 3-4). Duration of steroid taper, severity of initial irAEs, and use of additional immunosuppressants did not predict for toxicity on rechallenge, although patients remaining on steroid therapy at anti-PD-1 resumption had higher rates of toxicities (55% vs. 31%).

Patients who discontinued CTLA-4/PD-1 blockade for severe irAEs had relatively high rates of recurrent or distinct toxicities with anti-PD-1 resumption. However, many patients, particularly with combination-induced colitis, tolerated anti-PD-1 rechallenge well, and this approach can be considered in select patients.

Clearly, not a walk in the park for some...but a return to nivo alone after a reaction to the ipi/nivo combo proved doable for about 60% of these patients with significant reactions requiring immunosuppression therapy for their side effects!  

Take care ratties!!  It's a tough world at NIMH!!!! - c