Excellent PDF on how to deal with adverse events due to anti-PD1!!!!

 Check out the link below to read the file for yourself!!!

Management of adverse events following immunotherapy

None of it is really NEW news....but there is a great table of incidence of adverse events and some algorithms for management of adverse events broken down by body system.  Here are some pics:

Check out the link for a better view.  If I were dealing with any of these problems...or even thought I might be...I'd take this report to my doc for a discussion!!!  Yours, c

A beautiful visit to a beautiful city....Nice - 2006

We climbed up to see the view...

...along with many others.

Ten years ago...and just like yesterday.

A lizard was happy to take advantage of a dropped cerise during our picnic lunch.

Such loveliness seems almost unreal.

How can the human mind possess such hatred and the desire to harm those they do not know?

I haven't much to offer in return, but to France and it's people, especially those along the coast in Nice and Antibes, I thank you for what you have shared with me and mine.  Je suis desole pour tout ce que vous avez perdue. (I am sorry for all that you have lost.)

Despite political craziness, the nutty world unrest, the frightening bent of those who prefer racist views, the hatred, bullets, and malicious acts some employ to bring grief and harm, not to mention the devastation of hunger and disease... I still contend that the world remains a beautiful place.

We just have to do our best...

...enjoy our small successes...

...and pay attention to the beauty all around us, especially to the strength of spirit of those who run after malevolent beings driving trucks into pedestrians, who spread love not hate, who show us how to overcome the horror, so unfortunately spread, by a despicable few.  

I've got to believe that just like mayhem...joy, peace, shared knowledge, and allowing ourselves to be guided by the better angels of human nature...from within and without...is contagious...and will succeed in making the world a better place.  Much love to the beautiful city of Nice and to each of you. - c

Sew Chaotically! - Full skirted shirt dress - Simplicity 8014

I looooooove this pattern!!!  Using Simplicity 8014, I had already made this style:

...which sewed up perfectly and I blogged about here!!!  I found the material for my new one serendipitously at JoAnn's and knew it would be great for the fuller version.  It feels like a knit, but is a textured woven that is very soft, has some structure, yet hangs nicely.  It washes and dries without a single wrinkle!!  All the dresses from this pattern have been given rave reviews.  Here are two posts about my latest version:
Oona's version
Another from MimiG


With this as my inspiration: 

I was tempted to incorporate both sides of the fabric in my design....maybe making the sleeves and collar of one and the body of the dress from the other.  In the end...I decided to stick with a more classic look....

All the parts go together really well.

There was only one hiccough...which Oona mentioned and Mimi didn't.  Per the pattern, the back should have two tucks on either side at the waist just as the front bodice does.  However, when left like that, there was A LOT of fabric floating around and wadding up at my upper back!!!  So.....I made something like curved darts from each fold to take up the superfluous material and retain the pattern's pretty shape.  You can see a detail shot below....

I think it turned out okay!  Check out the print placement on all 4 of those pieces.  And, yes!!  I meant the collar to be like that!!  I'm tickled that I managed it!

It twirls!!!

B has dubbed it the "Paris Dress"!!!  Works for me! Sew Chaotically!!!  love, c

Intralesional Therapy....and patterns of response from the T-VEC OPTiM trial

Y'all know I'm pretty stoked about various intralesional therapies...

There is this on Rose Bengal/PV-10:  Intralesional PV-10, positive treatment for in-transit melanoma (with a link to ASCO report within)

This on CAVATAK:  ASCO 2016: CAVATAK intralesional therapy derived from the coxsackie virus

And this (containing links to many articles) on T-VEC:  ASCO 2016: T-VEC/talimogene laherparepvec with pembro

Now there is this: 

Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial.  Andtbacka, Ross, Puzanov, et al.  Ann Surg Oncol. 2016 Jun 24.   

Talimogene laherparepvec (T-VEC) is an oncolytic immunotherapy designed to induce tumor regression of injected lesions through direct lytic effects, and of uninjected lesions through induction of systemic antitumor immunity. In this study, we describe the patterns and time course of response to T-VEC from the phase III OPTiM trial of 436 patients with unresected stages IIIB-IV melanoma.

Lesion-level response analyses were performed based on the type of lesion (injected or uninjected cutaneous, subcutaneous, or nodal lesions; or visceral lesions [uninjected]), and the best percentage change from baseline of the sum of products of the longest diameters was calculated. Patients randomized to T-VEC (n = 295) who experienced a durable response (continuous partial or complete response for greater/= to 6 months) were evaluated for progression prior to response (PPR), defined as the appearance of a new lesion or greater than 25 % increase in total baseline tumor area.

T-VEC resulted in a decrease in size by greater than/= to50 % in 64 % of injected lesions (N = 2116), 34 % of uninjected non-visceral lesions (N = 981), and 15 % of visceral lesions (N = 177). Complete resolution of lesions occurred in 47 % of injected lesions, 22 % of uninjected non-visceral lesions, and 9 % of visceral lesions. Of 48 patients with durable responses, 23 (48 %) experienced PPR, including 14 who developed new lesions only. No difference in overall survival was observed, and median duration of response was not reached in patients with PPR versus those without PPR.

Responses in uninjected lesions provide validation of T-VEC-induced systemic immunotherapeutic effects against melanoma. PPR did not negatively impact the clinical effectiveness of T-VEC.

For what it's worth.... - c

New trial recruiting!!! Pembro plus MGA271 for folks (melanoma, urothelial cancer and more) who progressed on systemic therapy including immuno!!!

Y'all know I am apt to get excited about small things...but....this seems to hold real promise for folks who have progressed on a variety of treatments.  This study combines MGA271 with pembro for a variety of folks with solid tumors.  So what is this MGA271?  At the moment it is called Enoblituzumab, a B7-H3 monoclonal antibody.  Here's a link to a presentation that explains, followed by selected slides:

Interim results of an ongoing Phase 1, Dose escalation study of MGA271 (Enoblituzumab) an Fc-optimized humanized Anti-B7-H3 monoclonal antibody, in patients with advanced solid cancer

 

What is super cool about all of this...is....  See the second line on the slide above?  These folks are POST ipi, anti-PD1 or some various combo of the two!!!

Here is a link to a report of the new trial for Enoblituzumab combined with Pembro:  A Phase I, open-label, dose escalation study of MGA271 in combination with pembrolizumab in patients with B7-H3-expressing cancer

Here's a link to the study at ClinicalTrials.gov:  Safety Study of MGA271 in Combination With Pembrolizumab in Refractory Cancer

The trial seems to be actively recruiting in Baltimore, New York, Philadelphia, and San Antonio.  Now this is a Phase 1 study...making the ratties - ratties for realz!!! But....everybody gets the drug.  Just thinking this may be a real option for folks for whom neither ipi nor the anti-PD1 products worked.  (We'll keep looking at how it does, Joshie!!!!)

Good thing ratties have long tails!!!  love, c

Sew Chaotically! - Waste not, Want not #2

Since I had made myself this dress from New Look 0926 ...

...and Rosie this dress from New Look 6125.

I figured with the remnants, these tops were in order!!!

Yes, they are from from McCall's 7093!

And YES they are numbers 5 and 6 from that pattern!!!  It's been fun, but they are the last I am going to make from that pattern for a good, long time!!  Waste not want not!!! Sew chaotically!! - c

??? reason for latency....time between attacks....in some melanoma patients

Melanoma lesions independently acquire T-cell resistance during metastatic latency.  Zhao, Sucker, Horn, et al.  Cancer Res. 2016 Jun 3.
 
Melanoma often recurs after a latency period of several years, presenting a T cell-edited phenotype that reflects a role for CD8+ T cells in maintaining metastatic latency. Here we report an investigation of a patient with multiple recurrent lesions, where poorly immunogenic melanoma phenotypes were found to evolve in the presence of autologous tumor antigen-specific CD8+ T cells. Melanoma cells from two of three late recurrent metastases, developing within a 6-year latency period, lacked HLA class I expression. CD8+ T cell-resistant, HLA class I-negative tumor cells became clinically apparent 1.5 and 6 years into stage IV disease. Genome profiling by SNP arrays revealed that HLA class I loss in both metastases originated from a shared chromosome 15q alteration and independently acquired focal B2M gene deletions. A third HLA class I haplotype-deficient lesion developed in year 3 of stage IV disease that acquired resistance towards dominant CD8+ T cell clonotypes targeting stage III tumor cells. At an early stage, melanoma cells showed a dedifferentiated c-Junhigh/MITFlow phenotype, possibly associated with immunosuppression, which contrasted with a c-Junlow/MITFhigh phenotype of T cell-edited tumor cells derived from late metastases. In summary, our work shows how tumor recurrences after long-term latency evolve toward T cell resistance by independent genetic events, as a means for immune escape and immunotherapeutic resistance.

Basically, this is saying that when these researchers looked at different mets, they found that the individual tumors became resistant by modifying their surface molecule presentation making attack by the existing t-cells ineffective.  How? Why? Research like this is coming closer to answers we need in order to figure out what can be done to PREVENT the development of resistance!!!

I was lucky enough to go almost five years between my first cutaneous melanoma (with a positive node - 2003 to late 2007) with no treatment other than surgical excision of the area and nodal basin, as there was none other than interferon.  But in 2007, I was dealing with another cutaneous lesion, no positive nodes.  After another resection of the lesion and that nodal basin - I developed brain and lung mets three years later in 2010.  I have some dear ones who went 7, 10, 15, 17 YEARS between initial lesions and subsequent development of Stage IV melanoma.  What EXACTLY protected us?  What PRECISELY caused the ultimate failure of our immune systems?  These are answers we need to find!!!  I have pondered and researched this before.  I published this in 2012:  What I've been saying about 'indolent melanoma'!

While some of us get lucky with relatively indolent disease, and treatments have improved, too many precious peeps are diagnosed at Stage III or IV and are gone within a couple years, often after trying every treatment out there.  THIS IS NOT OK!  I guess I'll stop and try to settle down...for now. love, c