Wednesday, July 28, 2021

Summer Bounty!

It has been a blessed summer for me.  Brent and I have shared our usual silly and easy moments.  All four of the kiddos have been working hard, but have enjoyed moments of play as well.  Simple joys.  The beauty of small things.  Life unfolding. 

Our bit of garden has been paying dividends.  Shade over most of our property limits the fruits and veg we can grow a great deal.  But this year our three little tomato plants and a few more pepper plants have really come through.  We have had many many tomato salads.  B has eaten, shared, pickled and dried BUNCHES of peppers.  We have enjoyed greens early and recently!  Our blueberries have done incredibly well!  Despite sharing with the birds, I have made numerous pies, muffins and frozen many batches, still leaving plenty to eat with yogurt and share with friends.  The herbs have been a joy.  I use tarragon, basil, oregano, parsley, sage, or thyme in every meal and share with all who will take it!!!  Simply delicious pleasures!  I missed getting snaps of the beauty that has been my day lily bed.  It has been glorious.  But, these beauties have been filling our world with color in the past weeks...










And then there's Te veo!  You can't leave her out - cause she won't let you!!!  

As Jeanne says, "Life is good!"  Wishing you a bountiful summer, filled with joys - large and small.  Stay safe and well.  Much love, les.

Thursday, July 22, 2021

Sew Chaotically! ~ Quilt #2 - Sashiko Crazy!

 

I've had this quilt running around in my head for a while!!!  It started upon seeing this pic in 2017.  The Sashiko by volunteers, 2012, Textile Museum of Canada. 

That inspo set me off on a variety of sashiko projects!  A Tessuti Annie Dress, as a top.   An embellished Lisette, B6464.   New pillows in 2020.  



This Kalle top I just realized I never blogged, from October 2020.  Stitched up in linen. Combined with Nani Iro Sewing Studio pattern book pants.





Somewhere in 2019, I started playing around with Sashiko on squares of denim harvested from jeans Roo didn't want anymore.  As I made more of them, I realized ~ maybe I could make the Sashiko quilt of my dreams!!!

In late 2019 Bentie made me a quilting frame!!!  I wrote about it here:  Sew Chaotically! ~ The best dude and the quilt frame he built!!!



I decided I needed to practice on a smaller scale than my grand Sashiko Quilt and so I stitched up a 60 X 60 quilt top from scraps using the Carolina Chain Quilt pattern.


Initially planned as a nice house warming gift for a dear one, sentimental B fell in love with it.  So - as my first ever real live quilt - I got it finished for him for Valentine's Day! 

With no more excuses, I finished all the needed sashiko embellished denim squares, picked and purchased material for the quilt top and backing.  Machine hemmed said squares, then machine stitched them onto the quilt top.  Using a hera marker, I traced a curvy template for quilting stitches between the squares and along the borders.  I used Quilters Dream 80/20 cotton/poly batting for the first quilt and will be using it again as I was very happy with the result.  But, for this one, B encouraged the use of a super nice silk, bamboo, tencel and cotton blend, also from Quilters Dream.  I am really glad I did as it matched the weight of the top and fluffed nicely after washing!  In March I loaded it on the frame with B's help. (She's a BIG girl!!!) and I was off.  I used DMC cotton perle #8 floss as I did for B's quilt and finished her up earlier this month!


For the binding, I simply turned and machine stitched the top to the back.  I had intended to hand stitch it, which I like doing, but was afraid it wouldn't be strong enough, given the weight of the quilt.



I made pillow cases to match along with a throw pillow since I had one extra square!

Getting a detail pic of the stitching is difficult!



I am ever so tickled with how it turned out!!  Thanks for your enduring support, B!!!  You make all my dreams possible!   ~ les

Thursday, July 15, 2021

June Reads

My June reads were a mixed bag of topics, writing styles, re-readable words and un...

Pianos and Flowers - Alexander McCall Smith.  Unrelated short stories, each inspired by a photo.  Not his best work, to my mind.  I missed the development of characters you come to love that he creates so well in his other works.

Ordinary Life - Elizabeth Berg.  Short stories that deal with a wide variety of topics, from death to cancer, to failed marriages, to aging, to the mixed up mess that relationships can be.  Some were excellent.  Others were okay.

The Year of Magical Thinking - Joan Didion.  Had not known Ms. Didion before this read.  Interesting, if somewhat strange, woman.  Her heartache and confusion at the loss of her husband are palpable.  What appears to be name dropping, a gentrified and star filled lifestyle are a bit much for someone who simultaneously claims to have been without and appreciative only of art and the simple life, are distracting and disconcerting.  Still, her writing is addictive.  As follow up, I watched The Center Will Not Hold, a documentary about her done by the son of her brother-in-law.  It was a generous portraiture, but shared the breadth of the work that Joan and her husband, John Dunne, had produced in their life times.  It also presents Didion as one who lives her life somewhat disengaged; an observer.  This article in The New Yorker shares an anecdote that spoke loudly to me as well ~ The Most Revealing Moment in the New Joan Didion Documentary  Such detachment and the view of life as a stage undoubtedly makes a good reporter and story teller.  But, it leaves a lot of questions, too.

Blue Nights - Joan Didion.  As if one loss was not enough, she writes, though more briefly, of the loss of her daughter, whose illness began just before the death of her husband and whose eventual passing took place only 2 years later .  Most of the medical aspects made little sense to me if we are talking about the death of a perfectly healthy 37-39 year old from flu followed by a head injury and pancreatitis, though Didion is not explicit in many of those physiologic details.  Perhaps this article fills in the missing gaps ~  Is Joan Didion in Denial About Her Daughter's Alcoholism?  It is clearly Didion's choice as to what she prefers to share.  Perhaps there is just too much pain in her daughter's life and death to hear within her heart, much less put on the printed page.  I have no idea how one would survive the losses she endured in such rapid succession.  This report from NPR, notes the honesty with which she did acknowledge some of her experiences with motherhood ~ Sorrowful 'Blue Nights': Didion Mourns Her Daughter  Not sure we could be friends, but I do admire this formidable woman.

Blood, Bones & Butter - Gabrielle Hamilton.  Read as the mother of a chef, who reported that it included the most accurate description of brunch in a busy kitchen ever written.  I wanted to like this and its chef/author more than I did.  However, some of her stories seemed implausible.  Maybe my world is/was too sheltered.  But, still.  What makes for a good yarn can imperil the whole when you claim to be telling events as they really happened.  Or maybe I'm just a Doubting Thomas.

When Breath Becomes Air - Paul Kalanithi.  Painfully beautiful.  If this story doesn't make you appreciate every breath, I don't know what will.

How We Die:  Reflections of Life's Final Chapter - Sherwin Nuland.  A re-read for me, having first read these pages at the age of 40 following my initial diagnosis of Melanoma Stage IIIb.  It still demonstrates truth and integrity.  Much like learning that chicken doesn't simply materialize as cellophane wrapped skin, bone and feather free blobs of meat on a plastic tray, death doesn't come conveniently processed either.  Nuland makes it clear that death, a natural and unavoidable part of life, often includes pain and misery with an "easy death" being one of magical thinking. Death should be looked upon with neither horror nor the false expectation of falling into a fairy tale slumber.  Through his honest telling of his experiences with death and disease, we are left with the natural aspect of what it is, what modern medicine can and cannot do, the strength of the human spirit, and yes - hope.

Kitchen Confidential - Anthony Bourdain.  Crazy ass stories of the back of the house, running restaurants, and the life of a chef that, this time, ring true.  He does not get out of his scrapes and drug use magically or make tons of money serving drinks in a New York bar in the 80's as Hamilton reports.  He pays the price - in lots of ways.  A re-read because my chef is reading it.  I miss you, Tony.

A strange collection of words perhaps, but that was where my thoughts were floating in June.  Short stories about random moments that make up life.  Books about death that point to better ways to live.  Tales and lessons from those who feed us.  ~ les

Tuesday, July 13, 2021

Forever Changed - Quality of Life after Melanoma (and how to help) - Research from 2019 to ASCO 2021


Very few folks really grasp what it is like to LIVE with cancer - unless you are that person.  Granted, if you are lucky, as I am, you have a few of those understanding peeps in your life, but most folks want to move on from the whole experience.  The cancer patient doesn't have that luxury.  Obviously, we cancer peeps approach our existence in different ways.  Some are almost paralyzed by fear of cancer's return.  Some are able to deal with things fairly well until some "symptom"- likely caused by something completely unrelated, crops up - leading to absolute and debilitating certainty that their cancer is back.  Others are undone by follow-up scans and the anxiety awaiting results provokes.  Even the thought of  lovely future events, become almost frightening and worrisome in the life of a cancer patient as we have less certainty of being around to enjoy them than does the average cancer-free person.  While some of us, due to our own personality, the support we have, the approach we take to life (and death), and just simple quirks of fate, deal with our cancerous existence more easily, we ALL face fearful moments.  When dealing with only one cancer diagnosis, albeit Stage IV melanoma, BEFORE I was able to attain systemic treatment of any sort, but AFTER the removal of the upper lobe of one lung and radiation to a brain met, I wrote this:  Looking forward - September 2010  And here, in 2018, NED for melanoma for 8 years, but unaware that in a few short months I will be diagnosed with an incredibly rare Ex-goblet cell adenocarcinoma of the appendix, I penned this:  Where I've been, where I'm going ~ Fractals!    Then, in the midst of chemo for Cancer #2, these were my musings:  Polka dot binding personally produced ~ Possible inspo #SEWFROSTING ~ and Profound Ponderings

That's a smattering of my approach to dealing with MY life with cancer - here's what the data shows:

Health-related quality of life, emotional burden, and neurocognitive function in the first generation of metastatic melanoma survivors treated with pembrolizumab: a longitudinal pilot study.  Rogiers, Leys, DeCremer, et al. Support Care Cancer. 2019 Nov.

The aim of this study was to assess the evolution of health-related quality of Life (HRQoL), emotional burden, and neurocognitive function in the first-generation metastatic melanoma survivors treated with pembrolizumab.

Survivors were defined as patients who achieved a durable remission for at least 6 months after initiating pembrolizumab in a single-center observational study (N = 141). A semi-structured interview was performed at baseline. Neurocognitive computerized testing and patient-reported outcomes were collected at 4 time points to assess HRQoL using the EORTC QLQ-C30 and the HADS to assess anxiety and depression.

Out of 35 eligible patients, 25 were recruited and completed baseline assessment (18 female; median age 58 years [range 28-86]; 24 completed the 1-year follow-up phase. Median time since diagnosis was 30 months (range 12-84); median time since initiation of pembrolizumab was 19 months (range 6-42). At all visits, survivors reported a significantly lower global HRQoL, lower physical, emotional, cognitive, role, and social functioning compared with the European Mean of the healthy population. Fifteen patients (64%) had clinical levels of anxiety/depression at one time point during follow-up. The clinical interview revealed that 12 patients (48%) suffered from Cancer-Related-Post-Traumatic-Stress disorder, of whom 7 (28%) developed transient suicidal ideation, 1 patient made a suicide attempt. Neurocognitive testing revealed cognitive impairment in 8 patients (32%).

Metastatic melanoma survivors, treated successfully with pembrolizumab, are at risk for suffering from emotional distress and neurocognitive impairment with a persistent impact on their HRQOL. Timely detection in order to offer tailored care is indicated.

More than half of the 25 peeps in this study - 30 months post their melanoma diagnosis and 19 months since starting pembro - experienced significant anxiety/depression, almost half suffered from traumatic stress, and more than a quarter pondered suicide, with one attempting.  Not that we needed a study to tell us, but even effective treatment for melanoma leaves many with scars.

Then, there's this:  

Longitudinal associations between coping strategies, locus of control and health-related quality of life in patients with breast cancer or melanoma.  Toscano, Blanchin, Bourdon, et al.  Qual Life Res.  2020 Jan 1.

A diagnosis of breast cancer or melanoma is a traumatic life event that patients have to face. However, their locus-of-control (LOC) beliefs and coping strategies as well as the associations with health-related quality of life (HRQoL) changes over time are still not well known and rarely compared by cancer site.

The objective of this longitudinal study was to assess the association of LOC (Cancer Locus-of-Control Scale) and coping (Brief Cope) changes, with change in HRQoL (EORTC QLQ-C30) over time in newly diagnosed breast cancer and melanoma patients at 1, 6, 12, and 24 month post-diagnosis. Mixed models were used to compare LOC and coping longitudinal changes as well as their associations with HRQoL changes in early-stage breast cancer and melanoma patients.

Overall, 215 breast cancer and 78 melanoma patients participated in the study. At baseline, HRQoL levels were often higher for breast cancer compared to melanoma patients. For breast cancer and melanoma patients, negative coping strategies and perceived control over the course of illness were negatively and positively associated with HRQoL changes, respectively. For breast cancer patients only, emotional coping and internal causal attribution were negatively associated with HRQoL changes. For both cancer sites, living with a partner correlated with worse HRQoL.

Understanding coping strategies and LOC beliefs used by patients soon after their cancer diagnosis and over the course of illness can help identifying psychological and supportive care to modify maladaptive thoughts and beliefs and promote more adaptive behaviors to ultimately improve patients' well-being and HRQoL.

To be honest, not entirely sure what this word salad is saying - other than how folks respond to life after the life changing experience of either breast cancer or melanoma varies and is impacted by many things.  I do think having almost 3 times the number of breast cancer patients than those with melanoma may well skew any comparisons made between the two.

Then, this:

Patient-reported outcomes in melanoma survivors at 1, 3 and 5 years post-diagnosis: a population-based cross-sectional study.  Lisy, Lai-Kwon, Ward, et al. Qual Life Res. 2020 Mar 5.

There is a lack of population-based data describing patient reported outcomes (PROs) in melanoma survivors which could guide the development of interventions and resources. This study assessed overall quality of life (QoL), self-reported symptoms and unmet information needs in melanoma survivors 1, 3 or 5 years post-diagnosis.

A cross-sectional postal survey was conducted in Victoria, Australia, with eligible melanoma survivors identified from a population-based cancer registry. Patient-reported outcome measures included the EuroQoL 5-Dimension 5-Level (EQ-5D-5L), and self-reported symptoms, difficulties and information needs. Associations between demographic, disease and care-related factors and QoL were also assessed.

A total of 476 melanoma survivors participated in the study (response rate 46.5%). Anxiety and depressive symptoms were more prevalent in survivors compared to the general population (30.7% vs 21.6%). Fear of cancer recurrence (48.3%) and fear of cancer spreading (37.8%) were the most commonly reported symptom items, and approximately one in five melanoma survivors had unmet information needs related to psychological aspects of living with melanoma. Recurrent melanoma, living in a nursing home, chronic comorbidities, and melanoma diagnosed at greater than 2 mm thickness were associated with lower QoL.

A large proportion of melanoma survivors reported ongoing quality of life deficits, fear of cancer recurrence, as well as unmet information needs up to 5 years after diagnosis. Patients may benefit from tailored informational resources and interventions that address the psychological aspects of living with and beyond melanoma.

Among these 476 melanoma peeps, the researchers found they were more anxious and depressed than the average Joe.  (Gotta love science!) Almost half feared a cancer recurrence and over a third feared cancer spreading.  One in five felt that they were not coping well and had no support to facilitate improvement in that regard.  Being in a nursing home, having other illnesses or a more vicious melanoma diagnosis made things worse.  Well, duh!

Now, this:

Feasibility and Acceptability of Fear-Less: A Stepped-Care Program to Manage Fear of Cancer Recurrence in People with Metastatic Melanoma.  Lynch, Katona, Jefford, et al.  J Clin Med.  2020 Sept.

Immunotherapies and targeted therapies have revolutionized treatment of metastatic melanoma and improved survival rates. However, survivors treated with novel therapies are vulnerable to high levels of fear of cancer recurrence or progression (FCR). Existing FCR interventions have rarely been trialled in people with advanced cancer. The current study aimed to evaluate the acceptability and feasibility of Fear-Less: a stepped-care model to treat FCR in people with metastatic melanoma treated with immunotherapy or targeted therapy. Sixty-one outpatients with metastatic melanoma were screened using the Fear of Cancer Recurrence Inventory Short Form (FCRI-SF) and Fear of Progression Questionnaire Short Form (FoP-Q-SF). Survivors with subthreshold FCR were stratified to a self-management intervention while those with clinical levels of FCR were provided with an individual therapy, Conquer Fear. Survivor experience surveys and rescreening were administered post-intervention completion. Results indicated that Fear-Less was an acceptable and feasible FCR intervention. Results provided preliminary support for the potential impact of Fear-Less in reducing FCR. Fear-Less is a promising first step in providing an acceptable and feasible stepped-care model to treat FCR in survivors with metastatic disease.

Not clear what the Fear-Less intervention provided, but I would say it is likely that should ANYONE in the cancer care circle provide attention, interest and support to and for the stress cancer and its treatments engender - it would be beneficial.

And finally, this from ASCO and the Wizard:

Association of health-related quality of life (HRQoL) and treatment safety with nivolumab (NIVO) in patients (pts) with resected stage IIIB/C or IV melanoma: Analysis of CheckMate 238 four-year follow-up (FU) data.   Weber, Gogas, Sun, et al.  ASCO 2021.

Background:  In CheckMate 238, NIVO 3 mg/kg vs ipilimumab 10 mg/kg showed significantly longer recurrence-free survival and a lower rate of grade 3–4 treatment-related adverse events (TRAEs) in pts with completely resected stage IIIB/C or IV melanoma. This analysis assessed the association of long-term HRQoL and TRAEs in NIVO-treated pts in this trial.

Methods:  HRQoL was assessed using EORTC QLQ-C30 (global health status [GHS] and physical/emotional functioning) and EQ-5D-3L visual analogue scale (VAS) questionnaires administered after randomization, during 1 y of treatment (wk 5, 7, 11, 17, 25, 37, and 49), at posttreatment FU visits 1 and 2 (FU1 and FU2; 30 and 114 days after last dose), and at survival FU visits up to 4 y after last dose (EQ-5D-3L only). NIVO-treated pts were grouped based on whether they had experienced a grade 3–4 TRAE, any-grade TRAE leading to NIVO discontinuation, or any-grade select (immune-related) TRAE on treatment or up to 100 days after last dose. Longitudinal change from baseline (BL) in scores was assessed for pts with and without TRAEs having patient-reported outcome data at BL and greater than/= to1 post-BL assessment (HRQoL population) using descriptive statistics. QLQ-C30 subscale and VAS changes of 10 and 7, respectively, were considered clinically meaningful.

Results: The HRQoL population comprised 446 of 453 pts randomized to NIVO. EQ-5D-3L assessments were completed by 81% of survivors (263/324) after 4 y post-randomization. Grade 3–4 TRAEs occurred in 17% of NIVO-treated pts (77/446). A slight trend toward deterioration of GHS from BL on treatment was noted, with clinically meaningful deterioration at posttreatment FU1 and FU2. For the VAS, a similar trend on treatment was noted, with a clinically meaningful deterioration after NIVO discontinuation and a return to BL level by the start of survival FU. For pts without grade 3–4 TRAEs, mean change from BL scores remained stable (ie, no clinically meaningful deterioration on treatment or during FU). Any-grade TRAEs led to NIVO discontinuation in 9% of pts (42/446); HRQoL findings were similar to those for pts with grade 3–4 TRAEs. The most common any-grade TRAE was fatigue (35%). No clinically meaningful deterioration in VAS was noted for any select TRAE during FU except for hyperthyroidism (8%), with which deterioration occurred at FU1. EORTC QLQ-C30 physical and emotional functioning results will be presented.

Conclusions: In CheckMate 238, pts with TRAEs showed early HRQoL deterioration after NIVO discontinuation, but HRQoL returned to BL levels with no sustained deterioration during survival FU. Overall, HRQoL was maintained on treatment and over a long-term FU period in pts with resected melanoma receiving adjuvant NIVO. Clinical trial information: NCT02388906.

In this study, not surprisingly, folks felt pretty rough while on treatment, reporting a decreased "global health status".  Folks with side effects had it worse, especially those who had to stop Nivo due to those side effects.  But, overall, this report contends that folks made it back to baseline at a later follow-up.  Hmm, Weber.  Did they though?  First of all, it is important to note that these were (apparently) adjuvant patients - not advanced melanoma patients.  Secondly, there are many studies noting patients try to give their doc the answer they seem to want to hear.  Nobody's fault in any of this.  Just the way the cookie crumbles when doing a qualitative study.

So ~ What did we learn here?  Not much we didn't already know.  Cancer sucks.  Cancer and its treatments cause a great deal of physical distress along with anxiety and depression.  Nobody really knows how much, but it is clear that the more side effects you have, the worse off your health, and the less external support - the more difficult it all becomes.  Sadly, I have no answers.  Other than....
  • Do the best you can.
  • Know that you are not alone - even though it can feel very much as though you are. Everybody else is struggling to tread water, too!
  • Seek out, even though it is ever so hard when struggling, support resources - cancer groups (whether in-person or on-line), social services, help from friends and family.
  • Ask your oncologist for psychological support services.  Larger groups often have them in house.  Others can certainly refer you.
If you are a care giver, I'm sure figuring out "what to do" seems unknowable.  There are many resources on-line that give good tips.  These are a couple posts I put together (with links within the last) that you may find helpful - 

Wishing each of you my very best ~ les

Saturday, July 3, 2021

TIL - A report out of ASCO 2021 and incredible words from one of Melanoma's Most Fearless and Inspiring Leaders

TIL (adoptive cell therapy, using tumor infiltrating lymphocytes) has come a long way, which is a good!  In 2013, I lost a dear one, a family lost a beautiful wife and mother, students lost an incredible teacher, melanoma peeps lost a passionate advocate, and the world lost one hell of a woman when she died from melanoma and complications of TIL therapy.  This post was dedicated to her that year:  Ode to Pati....a fallen comrade.  I beg you to view her video via the link contained within and noted here:  Pati's video - What is one life worth?  She had so much to say.  So much yet to do.  Still, she did ever so much.

This post contains the thoughts of a another incredible human - and friend - who also happens to be an amazing melanoma peep who has beaten the odds REPEATEDLY!  A dedication he penned upon her death:  Beautiful words, from an amazing melanoma warrior, and friend~  

I don't post a great deal on TIL.  But the posts I have are here - containing explanations of what is involved and a few other reports -  TIL Therapy.  Currently, a variety of techniques have been developed and different choices need to be made when seeking this avenue of treatment that my posts do not begin to address.  Researchers are striving to make TIL more accessible and workable.  Now, there is this out of ASCO this year:

Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma: Evaluation of impact of prior anti-PD-1 therapy.  Larkin, Sarnaik, Chesney, et al.  ASCO 2021.

Background:  Immune checkpoint inhibitors (ICI) have become standard of care for treatment of metastatic melanoma. Most patients with advanced melanoma progress on ICI and treatment options are limited for these patients. Progression may be through primary resistance (lack of response) or secondary resistance (initial response then progression). Lifileucel is an adoptive cell therapy using TIL, that has shown efficacy in patients with advanced melanoma who progress on/after an anti-PD-1 (Sarnaik, 2020). We present the 28-month (mos) follow-up data and highlight the impact of prior anti-PD-1 response and duration of exposure on outcome with lifileucel.

Methods:  C-144-01 is a Phase 2, open-label, multicenter study of efficacy and safety of lifileucel in patients with advanced melanoma who have progressed on anti-PD-1 therapy and BRAFi ± MEKi, if BRAF V600+. We report long-term follow up on Cohort 2 (N = 66). Tumors were resected at local sites, processed in central GMP facilities for TIL production in a 22-day manufacturing process. Therapy consisted of nonmyeloablative lymphodepletion using 2 days of cyclophosphamide and 5 days of fludarabine, a single infusion of lifileucel, and up to six doses of IL-2. Objective response rate (ORR) was assessed by RECIST 1.1. Data cutoff was Dec. 14, 2020.

Results:  Baseline characteristics: 3.3 mean prior therapies (100% anti-PD-1; 80% anti-CTLA-4; 23% BRAFi/MEKi), high baseline tumor burden (106 mm mean target lesion SOD), 42% liver/brain lesions, 40.9% LDH greater than ULN. ORR by investigator was 36.4% (3 CR, one new CR developed at 24 mos; 21 PR). Median duration of response (mDOR) was not reached at median follow-up of 28 mos (DOR range: 2.2- 35.2 mos). In responders, the median cumulative duration and median prior lines of anti-PD-1 therapy was 4.4 mos (range: 1.4-22.5 mos), and 1.5 (range: 1-4). Data in Table demonstrates a meaningful increase in DOR to TIL with primary anti-PD-1 resistance and lower duration of time on prior anti-PD-1 therapy. No new safety risks have been identified for lifileucel during long-term follow-up.

Conclusions:  One-time lifileucel treatment results in a 36.4% ORR, and mDOR was not reached at 28 mos of median study follow up. One PR converted to a new CR at 24 months as responses continue to deepen. DOR is positively associated with primary resistance to prior anti-PD-1 therapy and with shorter cumulative prior duration of anti-PD-1 therapy. Lifileucel may offer a better clinical outcome when used earlier upon detection of progression on prior anti-PD-1 rather than retreatment with anti-PD-1 based regimens. Clinical trial information: NCT02360579.

So - these researchers have concluded that melanoma peeps who progressed on immunotherapy and BRAF/MEK inhibition (when BRAF positive) and were then treated with this particular TIL regimen -  attained an overall response of 36%.  Average duration of response was not reached at 28 months.  Interestingly, they note that those who had a better outcome were those who had failed anti-PD-1 early on and therefore had minimal exposure to anti-PD-1.  As such, they are recommending that folks who fail anti-PD-1 should pursue TIL then rather than try a re-do with anti-PD-1.

Hard decisions for sure.  Thanks ratties! And thanks forever, to you dear Pati.  You were and continue to be a woman who lived large and made the world a better place for all of us.  - c

Thursday, July 1, 2021

ASCO 2021 - LMD (leptomeningeal disease) in melanoma

I guess while we're on the subject of some of the most difficult things melanoma patients can deal with, we might as well roll with it.  LMD is certainly that.  Here are previous posts:  Leptomeningeal Disease

Now there is this:  

Intrathecal (IT) and intravenous (IV) nivolumab (N) for metastatic melanoma (MM) patients (pts) with leptomeningeal disease (LMD).  John, Foster, Haymaker, et al.  ASCO 2021.

Background:  MM pts with LMD have a dismal prognosis, with median overall survival (OS) less than 3 months, no approved therapies and extremely limited clinical trial options. We previously reported initial safety findings from an open label, single arm, single center phase I/IB trial (NCT03025256), in which IT and IV N were well tolerated, without any CNS-specific or unexpected toxicity. Here we report an update on safety and maximum tolerated dose (MTD) for all patients enrolled, and efficacy for the completed dose cohorts.

Methods:  MM patients aged greater than 18 with evidence of LMD by MRI and/or CSF cytology, ECOG PS greater than/= to 2 were treated with IT and IV N. Dexamethasone less than/= to 4 mg/daily and concurrent BRAF/MEK inhibitor(i) treatment was allowed. For cycle 1, IT N was administered via intraventricular reservoir on day (D)1. For subsequent cycles (every 14 days), pts received IT N on D1, followed by IV N 240 mg on D2. IT N doses evaluated were 5, 10, 20 mg and 50 mg. Blood and CSF were collected at multiple time points for translational research. The primary objectives of this first-in-human study were to determine the safety and MTD of IT N given with IV N in MM pts with LMD. Bayesian mTPI methodology was used to define the MTD.

Results:  To date, 23 pts have been treated: two at 5, three at 10, fourteen at 20 mg and four at 50 mg IT N. Median age at LMD diagnosis was 42 (28-73); 12 pts are male. All pts had radiographic evidence of LMD and neurological symptoms; 14 pts had positive CSF cytology at baseline. 21 pts received prior therapies for their metastatic melanoma: anti-PD1 (n = 19), BRAFi/MEKi (n = 14), chemo (n = 2), IT IL2 (n = 4) other (n = 2). 19 pts had prior XRT, including whole brain RT (n = 7). Two pts were treatment-naïve. The median number of IT N doses was five (1- 66). The combination regimen was well tolerated by all evaluable pts (n=23), with only five pts (22%) experiencing gr 3 AEs, and no reported gr 4 or 5 toxicities. Nausea (30%), diarrhea (26%), and rash (22%) were the most common AEs. Eight pts (23%) experienced AEs after IT N administration, all gr 1. Initial efficacy analysis included only pts (n=19) treated with first three dose levels (5-20mg). Median follow-up for these pts is 4.5 months (mos) (1.1, 31.5 mos) and median OS is 63 % at 3 mos, 42 % at 6 mos and 30% at 12 mos.

Conclusions:  The trial demonstrates the feasibility and safety of IT administration of modern immunotherapy for MM pts with LMD. No unexpected systemic or neurological toxicity was observed with 20mg IT N. 2 additional patients are required to complete the 50mg IT N cohort. OS rates at 6 and 12 mos are encouraging and support further evaluation of IT administration of immunotherapy agents for pts with MM and LMD. Final presentation will include results of LMD for all dose cohorts, composite response assessment and comparative analysis of longitudinal CSF samples to assess immunologic effects. Clinical trial information: NCT03025256.

Holding Rob and Adriana in my heart always.   ~ les