Neutrophil-to-lymphocyte ratios as a predictor of death from melanoma in patients with NONmetastatic disease

I've talked about Neutrophil-to-lymphocyte ratios before as prognostic predictor of a response to ipi/yervoy, noting that having an "....elevated absolute neutrophil counts as well as elevated neutrophil-to-lymphocyte ratios did not bode well for the 720 melanoma patients treated with ipi in this study.  The risk for progression and death was even greater when both of those values were increased.  This report is consistent with the findings from the initial, smaller study of  214 melanoma patients treated with ipi in which:  "Patients with baseline NLR (neutrophil-to-lymphocyte ratio) less than 5, had a significantly improved progression free survival and overall survival compared to those with a NLR equal or greater than 5."

Here's the link to both those reports:  Neutrophils as a prognostic predictor in patients treated with ipi/Yervoy

In this study, from different authors, the NLR is used as a biomarker in folks with NONmetastatic melanoma to predict potential for disease-specific death....

Elevated Blood Neutrophil-to-Lymphocyte Ratio: A Readily Available Biomarker Associated with Death due to Disease in High Risk Nonmetastatic Melanoma. Davis, Langan, Panageas, Postow, et al. Ann Surg Oncol. 2017 Mar 16.

Elevated peripheral blood neutrophil-to-lymphocyte ratio (NLR) is associated with poor oncologic outcomes in patients with stage IV melanoma and other solid tumors, but its impact has not been characterized for patients with high-risk, nonmetastatic melanoma.

Retrospective review of a melanoma database identified patients with high-risk melanoma who underwent operation with curative intent at a single institution. NLR was calculated from blood samples obtained within 2 weeks before operation. Multiple primary melanomas and concurrent hematologic or other metastatic malignancies were excluded. Cumulative incidence of death due to disease was estimated, and Gray's test was used to examine the effect of NLR on melanoma disease-specific death (DOD). Multivariable competing risks regression models assessed associated factors.

Data on 1431 patients with high-risk, nonmetastatic melanoma were analyzed. Median follow-up for survivors was 4 years. High NLR (greater/= to 3 or as continuous variable) was associated with older age, male sex, thicker primaries, higher mitotic index, and more advanced nodal status. On multivariate analysis, high NLR (greater/= to 3 or as a continuous variable), older age, male sex, ulcerated primary, lymphovascular invasion, and positive nodal status were all independently associated with worse DOD.


NLR is a readily available blood test that was independently associated with DOD in patients with high-risk, nonmetastatic melanoma. It is unclear whether high NLR is a passive indicator of poor prognosis or a potential therapeutic target. Further studies to evaluate the prognostic role of NLR to potentially identify those more likely to benefit from adjuvant immunotherapy may prove informative.

If this is so, then following these simple lab values may be super important in whether Stage III peeps should choose adjuvant treatment or not.  - c

BRAF/MEK rechallenge in folks who have had that treatment before

For those with BRAF positive melanoma who were treated with BRAF/MEK, perhaps went on to other things...but now are still in need of treatment...a rechallenge with BRAF/MEK can still offer some hope.   Here is the report:

Combination of dabrafenib plus trametinib for BRAF and MEK inhibitor pretreated patients with advanced BRAFV600-mutant melanoma: an open-label, single arm, dual-centre, phase 2 clinical trial. Schreuer, Jansen, Planken, et al. Lancet Oncol. 2017 Mar 3.

Patients with BRAF^V600-mutant melanoma benefit from treatment with the combination of BRAF and MEK inhibitors, but resistance and disease progression develops in most patients. Preclinical studies and case studies have indicated that acquired resistance to BRAF inhibition can be reversible. We aimed to assess the anti-tumour activity of rechallenge with BRAF plus MEK inhibition in a prospective clinical trial.

In this open-label, single arm, dual-centre, phase 2 academic study in Belgium, patients aged 18 years or older with BRAFV600-mutant melanoma who had previously progressed on BRAF inhibitors (with or without MEK inhibitors) and were off-treatment for at least 12 weeks, were treated with dabrafenib 150 mg orally twice per day plus trametinib 2 mg orally once per day. The primary endpoint was the proportion of patients with investigator-assessed overall response at any time (defined as complete response or partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed on two occasions, at least 28 days after the first response was recorded). Analyses were done in the intention-to-treat population. The study is ongoing but no longer recruiting patients. This trial is registered with ClinicalTrials.gov, number NCT02296996.

Between April 5, 2014, and Feb 2, 2016, 25 patients were enrolled and initiated treatment in our study. A partial response was documented in eight (32%) of 25 patients (six patients had progressed on previous treatment with dabrafenib plus trametinib and two patients had progressed on previous BRAF inhibitor monotherapy). Stable disease was noted in ten patients (40%). Rechallenge with dabrafenib plus trametinib was well tolerated. There were no unexpected or grade 4 or 5 treatment-related adverse events. Grade 3 adverse events occurred in two patients (8%; panniculitis [n=1] and pyrexia [n=1]). Serious adverse events which occurred on study were one patient with an Addison crisis triggered by grade 2 pyrexia symptoms that resolved after discontinuation of dabrafenib and trametinib. No patients died as a result of study treatment.

Rechallenge with dabrafenib plus trametinib showed anti-tumour activity in patients who had previously progressed on BRAF inhibitors and as such, rechallenge represents a potential new treatment option for these patients.

Blessings one and all - c

Side effects of immunotherapy - Part 8

In the ongoing saga...see the previous post:  Side effects of immunotherapy - Part 7

New-onset third-degree atrioventricular block because of autoimmune-induced myositis under treatment with anti-programmed cell death-1 (nivolumab) for metastatic melanoma. Behling, Kaes, Munzel, et al. Melanoma Res. 2017 Apr;27.

There has been considerable progress in treating malignant melanoma over the last few years. The immune-checkpoint-inhibitors nivolumab and pembrolizumab have been approved by the Food and Drug Administration in 2014 for the therapy of metastatic melanoma. Anti-programmed cell death-1-blocking antibodies are known to cause immune-related adverse events. Physicians should be aware of common and rare side effects and pay attention to new ones. We therefore report a severe and life-threatening side effect of anti-programmed cell death-1 immunotherapy with nivolumab that has not been previously reported: the development of a third-degree atrioventricular block. After a second infusion with nivolumab, our patient developed a troponin I-positive and autoantibody-positive myositis and a few days later a new-onset third-degree atrioventricular block. This is most likely because of an autoimmune-induced myositis with a cardiac impairment in terms of a myocarditis, which led to an impairment of the conduction of cardiac electrical stimuli.

Two cases of clinical myasthenia gravis associated with pembrolizumab use in responding melanoma patients. Nguyen, Kuo, Budiman, Christie. Melanoma Res. 2017 April.

Immune checkpoint inhibitors have changed the landscape of the treatment of multiple solid malignancies, and have been used increasingly in the recent years. Although usually well tolerated, given the relative inexperience of using immune checkpoint inhibitors, we are still learning of new side effects from the treatment. We report on two cases of ocular myasthenia gravis that occurred after treatment with pembrolizumab, an antiprogrammed-death (anti-PD1) monoclonal antibody for advanced melanoma in responding patients. One case is in an 81-year-old man and the second case in an 86-year-old woman, both with BRAF-negative metastatic melanoma receiving pembrolizumab. These two cases of ocular only associated myasthenic syndrome appeared 7 and 11 weeks after the initiation of pembrolizumab. We conclude that the condition is most likely associated with pembrolizumab as symptoms started after treatment with pembrolizumab, neither patient had other evidence of neurological cause for presentation, and symptoms also improved rapidly with administration of steroids. Both patients showed good oncological response to anti-PD1 treatment and one patient successfully continued to receive ongoing treatment with no further complications.

PD-1 inhibitors increase the incidence and risk of pneumonitis in cancer patients in a dose-independent manner: a meta-analysis. Wu, Hong, Zhang, et al. Lancet Oncol. 2017 Mar 3.

Therapies that targeted PD-1 have shown remarkable rates of durable clinical responses in patients with various tumor types. However, the extent and knowledge of pulmonary toxicities associated with PD-1 blockade, mainly manifested as pneumonitis, remains obscure. In this study, a total of 6360 subjects from 16 phase II/III clinical trials were pooled for meta-analysis to evaluate the overall incidence and risk of PD-1 inhibitors-related pneumonitis in cancer patients. The incidence of pneumonitis during anti-PD-1 immunotherapy was 2.92% for all-grade and 1.53% for high-grade pneumonitis. Compared with routine chemotherapy, PD-1 inhibitors were associated with a significant increased risk of pneumonitis. Moreover, among the types of tumor treated with PD-1 inhibitors, the melanoma patients have the lowest incidence of pneumonitis, while the non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) patients have the highest. Furthermore, no significant differences were detected in the incidences of all- and high-grade pneumonitis between high-dose and low-dose groups of PD-1 inhibitors. In conclusion, PD-1 inhibitors were probably associated with an increased risk of pneumonitis in a dose-independent manner, compared with routine chemotherapeutic agents. The frequency and severity of treatment-mediated pneumonitis was quite different in patients with various tumor types.

Autoimmune limbic encephalitis with anti-contactin-associated protein-like 2 antibody secondary to pembrolizumab therapy. Brown, Hissaria, Hsieh, et al. J Neuroimmunol. 2017 Apr 15.

Immune checkpoint inhibitors such as Pembrolizumab are used to restore antitumour immune response. It is important to be vigilant of immune mediated adverse events related to such therapy. We report a case of autoimmune limbic encephalitis with Contactin-Associated Protein-like 2 (CASPR2) antibody secondary to Pembrolizumab therapy for metastatic melanoma.

Acute symptomatic hypocalcemia from immune checkpoint therapy-induced hypoparathyroidism. Win, Thein, Qdaisat, and Yeung. Am J Emerg Med. 2017 Feb 27.

Ipilimumab (a monoclonal antibody against CTLA-4) and nivolumab (a humanized antibody against PD-1) target these immune checkpoint pathways and are used for treatment of melanoma and an increasing number of other cancers. However, they may cause immune-related adverse effects (IRAEs). Although many endocrinopathies are known to be IRAEs, primary hypoparathyroidism with severe hypocalcemia has never been reported. This is the first case of hypoparathyroidism as an IRAE presenting to an Emergency Department with acute hypocalcemia.  A 73-year-old man with metastatic melanoma presented to the Emergency Department for the chief complaints of imbalance, general muscle weakness, abdominal pain and tingling in extremities. He had wide spread metastasis, and begun immunotherapy with concurrent ipilimumab and nivolumab 1.5months ago. At presentation, he had ataxia, paresthesia in the hands and feet, and abdominal cramping. Magnetic resonance imaging of the brain was unremarkable. He was found to be hypocalcemic with undetectable plasma parathyroid hormone. He was admitted for treatment of symptomatic hypocalcemia and was diagnosed with primary hypoparathyroidism. Shortly afterwards, he had thyrotoxicosis manifesting as tachycardia and anxiety, followed by development of primary hypothyroidism. At 4months after the Emergency Department visit, his parathyroid function and thyroid function had not recovered, and required continued thyroid hormone replacement and calcium and vitamin D treatment for hypocalcemia.  Primary hypoparathyroidism caused by ipilimumab and nivolumab may acute manifest with severe symptomatic hypocalcemia. Emergency care providers should be aware of hypoparathyroidism as a new IRAE in this new era of immuno-oncology.

Be safe.  Be aware.  Seek help if you think you need it!  Hang tough, ratties!  Hang tough!  - c

What tangled 'paths' we weave: Nilotinib for KIT mutated melanoma and Buparlisib for the PI3K pathway in melanoma brain mets

Melanoma mutations can be confusing to say the least.  This diagram helps a bit:

Here's credit and an explanation:  Melanoma Pathways....A Melanoma Molecular Disease Model

NRAS and KIT mutated patients have not had the luxury of good responses to immunotherapy and targeted therapies currently being utilized in melanoma.  But, now there's this:

Efficacy and Safety of Nilotinib in Patients With KIT-Mutated Metastatic or Inoperable Melanoma: Final Results From the Global, Single-Arm, Phase II TEAM Trial. Guo, Carcjal, Drummer,..., Hodi. Ann Oncol. 2017 Mar 6. 

The single-arm, phase II Tasigna Efficacy in Advanced Melanoma (TEAM) trial evaluated the KIT-selective tyrosine kinase inhibitor nilotinib in patients with KIT -mutated advanced melanoma without prior KIT inhibitor treatment.

Forty-two patients with KIT -mutated advanced melanoma were enrolled and treated with nilotinib 400 mg twice daily. TEAM originally included a comparator arm of dacarbazine (DTIC)-treated patients; the design was amended to a single-arm trial due to an observed low number of KIT -mutated melanomas. Thirteen patients were randomized to DTIC prior to the protocol amendment removing this study arm. The primary endpoint was objective response rate (ORR), determined according to Response Evaluation Criteria In Solid Tumors.

ORR was 26.2%, sufficient to reject the null hypothesis (ORR less than or = to 10%). All observed responses were partial responses (PRs; median response duration, 7.1 months). Twenty patients (47.6%) had stable disease, 10 (23.8%) had progressive disease, and 1 (2.4%) response was unknown. Ten of the 11 responding patients had exon 11 mutations, 4 with an L576P mutation. The median progression-free survival and overall survival were 4.2 months and 18.0 months, respectively. Three of 13 patients on DTIC achieved a PR, and another patient had a PR following switch to nilotinib.

Nilotinib activity in patients with advanced KIT -mutated melanoma was similar to historical data from imatinib-treated patients. DTIC treatment showed potential activity, although the low patient number limits interpretation. Similar to previously reported results with imatinib, nilotinib showed greater activity among patients with an exon 11 mutation, including L576P, suggesting that nilotinib may be an effective treatment option for patients with specific KIT mutations.  

42 patients is not a ton.  26.2% ORR...with all of those being partial responses is not fabulous...but it is definitely SOMETHING!!!  Hey, I was over the moon when ipi was approved with its 15% response rate!!!  

And ~ if you refer to the chart above again...you will see the PI3K pathway....

Here is an initial post re the PI3K pathway in relation to brain mets by Dr. Davies:  PI3K/AKT - a pathway with potential for treating melanoma brain mets

And now there's this mousie medicine....

PI3K Pathway Inhibition Achieves Potent Antitumor Activity in Melanoma Brain Metastases In Vitro and In Vivo. Niessner, Schmitz, Tabatabai, et al. Clin Cancer Res. 2016 Dec 1.

Great advances have recently been made in treating patients with metastatic melanoma. However, existing therapies are less effective on cerebral than extracerebral metastases. This highlights the potential role of the brain environment on tumor progression and drug resistance and underlines the need for "brain-specific" therapies. We previously showed that the PI3K-AKT survival pathway is hyperactivated in brain but not extracerebral melanoma metastases and that astrocyte-conditioned medium activates AKT in melanoma cells in vitro We therefore tested the PI3K inhibitor buparlisib as an antitumor agent for melanoma brain metastases.

Buparlisib inhibited AKT activity, decreased proliferation, and induced apoptosis in metastatic melanoma cell lines and short-term brain melanoma cells, irrespective of their BRAF and NRAS mutation status. In addition, buparlisib inhibited hyperactivated AKT and induced apoptosis in melanoma cells that were stimulated with astrocyte-conditioned medium. The growth of tumors induced by injecting human BRAF- and NRAS-mutant metastatic melanoma cells into the brain of mice was significantly inhibited by buparlisib.

These results emphasize the value of targeting the PI3K pathway as a strategy to develop drugs for melanoma brain metastases.

This last is certainly in its baby steps...  But, hey!  On these paths, any steps at all are a needed start!!
(However, there are many PI3K inhibitors in studies for other cancers - Buparlisib [drug noted above] and Alpelisib [for breast cancer], Duvelisib [hematologic malignancies], TGR1202 [follicular lymphoma].)

Thanks, mousies.  Hang tough, ratties!  - c

Circulating DNA predicts response to anti-PD1

One more thing I have been yelling about for years!!!  Medicine now has the technology to determine all sorts of things via a simple blood draw. Circulating tiny bits of tumor DNA floating through our blood can tell docs what type of tumor we have, predict response to a given treatment and let us know how the treatment is working.  Here is a link to years of posts:  Circulating DNA in melanoma treatment from 2014 til now!!

Now there's this:

Circulating tumour DNA predicts response to anti-PD1 antibodies in metastatic melanoma. Lee, Long, Boyd, et al. Ann Oncol. 2017 Jan 24. 

Programmed death 1 (PD1) inhibitors are now a foundation of medical management of metastatic melanoma. This study sought to determine whether circulating tumour DNA (ctDNA) provides useful early response and prognostic information.

We evaluated the relationship between pre-treatment and early on treatment ctDNA and outcome in melanoma patients treated with PD1 inhibitors alone or in combination with ipilimumab.

ctDNA was detected in 40/76 patients (53%) at baseline, and correlated with stage, LDH levels, disease volume and ECOG performance. RECIST response was 72% (26/36) in Group A (undetectable ctDNA at baseline), 77% (17/22) in Group B (elevated ctDNA at baseline but undetectable within 12 weeks of therapy) and 6% (1/18) in Group C (elevated ctDNA at baseline and remained elevated during treatment). The median PFS was not reached in groups A and B and was 2.7 months for Group C. The median OS was not reached for Groups A and B and was 9.2 months for Group C . The poor outcome measures associated with Group C remained significant in multivariate analysis adjusted for LDH, performance status, tumour stage and disease volume. The predictive value for ctDNA for response was confirmed in a separate validation cohort.

Longitudinal assessment of ctDNA in metastatic melanoma patients receiving treatment with PD1 inhibitors is an accurate predictor of tumour response, PFS and OS. Patients who had a persistently elevated ctDNA on therapy had a poor prognosis, and this may guide combination and sequencing of subsequent therapies.

Clearly, per the results of this study, patients did best when their circulating tumor DNA became undetectable under treatment.  Conversely, as one might suspect, when ctDNA remained elevated despite treatment, folks did less well...even when researchers controlled for known prognostic indicators like LDH, disease volume, etc.

We KNOW these facts.  We HAVE the technical ability.  WHY is this not standard of care??

Hang in there, ratties.  love, c

Chaotic Cookery! - From Someone Else's Table: Turkey Legs Confit

Duck legs confit in Sarlat, France. Roast lamb that was basically a confit in Spain (pic below). Turkey leg confit in Chicago at the Purple Pig.  Now......Turkey Legs Confit.....at home in TN!!!

For my attempt I basically adapted a Bon Appetit recipe for Chicken Leg Confit.

Turkey Leg Confit:  Salt and pepper two turkey legs.  Place in a baking dish in which the legs fit with as little extra space as possible. Cut 1 bulb of garlic in half.  Quarter 2 shallots.  Leave paper on all and tuck them in between and around the legs.  Toss in thyme sprigs.  Come close to covering the legs with olive oil.  Cover and place in oven at 275 for 3 hours.  Then, uncover and cook for 30 more minutes.  This can be done as much as 2 days before serving.  And....don't fret about all the oil.  You will not have oily legs and the flavored oil can be used in more roasted bird, with roasted potatoes or other veggies.

Prepped and ready for the oven.

First step done!

Ready to eat!!!

Once your are ready to serve.  Remove the legs from their oil bath.  Place on oven safe tray or pan and roast at 425 for about 15 - 20 minutes until browned and skin crisp.

So yummy and easy!  What an elevation for lowly legs.  And....about those sides....

B's Spicy Roasted Potatoes with Cool Yogurt Dipping Sauce - from Williams-Sonoma's New Flavors for Vegetables

Cut about 3 pounds of peeled russet potatoes (any kind really) into bite sized pieces and toss with 2 T Harissa (B decreases the amount for my whimpy self), 1/4 t cayenne, 1 T sesame seeds, and 1 t salt.  Meanwhile, heat a roasting pan with about 1/4 c oil (in this case we used the oil the turkey legs were cooked in!!) drizzled in the bottom.  Once it is hot, carefully add the potatoes and toss them to coat in the oil.  Arrange the potatoes in a single layer.  Roast until the potato pieces are nicely browned, 25-30 minutes.  Flip over and roast until tender and browned and crisp outside, about 15 minutes longer.

While roasting - mix up a yogurt sauce with 1 cup Greek yogurt, 1/2 bunch fresh copped mint (or parsley or dried herbs), and juice from 1/2 lemon.  Season with salt and pepper.

For this dinner, I also sauteed some chard with the roasted scallions and some of the garlic and oil from the turkey legs.

So yummy....Try it!  Turkey legs influenced by tables in Spain and France....not to mention Chicago!!!  You can never go wrong eating and cooking - From Someone Else's Table! - c

Think Obama Care vs Trump Care is just partisan bickering? NOPE! It is all about LIFE and HEALTH for you and those you love!

I know, I know!!!!  There is absolutely no greater mood killing, depressing and dismaying topic to discuss than insurance or politics!  And, in this context...we have both!!!  In the words of the Tweeter-in-chief, "SAD!!!!" Still, Obama Care vs Trump Care is too important to ignore!  So....here we go....

This is an amazing video that breaks it DOWN!!!

Ezra Klein: The perverse reality of the Republican health care bill

This is a particularly telling interview from NPR of an ex-insurance exec ~ and you know how much I love those vultures!!!

Insurance Industry Worried By GOP Plan To Replace Obamacare, Consultant Says

And who always suffers the most when folks who think the "bottom line" matters more than people, call the shots?  The poorest, sickest, oldest, youngest - our most vulnerable:

From The Atlantic: The Silent Victims of the GOP Health-Care Proposal “Children are the largest single group of beneficiaries on Medicaid—and they don't vote.”

If you think "Obama Care" didn't help you and yours because you have private insurance, you have a lot to rethink!!!

The ACA forced insurance companies to abandon lifetime caps!  Grand totals paid out by insurance plans, no matter that a family has paid into them for years, but ended all future payments for your dad, because after he had ONE significant surgery he maxed out his policy (never mind that he had never used it before)!  Or, your baby was no longer covered by your family plan because she stayed a few nights in the NICU right after birth. Before the ACA, that was it! No more payments.  No more coverage, you were done - UNTIL the ACA changed that horrific policy and made insurance companies play fair!

The ACA forced insurance companies to stop discrimination against those of us with pre-existing conditions.  And if you think melanoma and cancer were the only "pre-existing" diagnoses that allowed insurance companies to charge you more or not sell you insurance at all...at any price...well, that's not true.  Children with a history of a broken leg at age 4, which healed perfectly, found themselves uncovered at all or just not "that leg" should, heaven forbid it suffer an injury in an accident, football game, or develop a sarcoma.  And folks with high blood pressure, diabetes, or  a heart attack...well, they could just forget it.

The ACA stopped insurance companies from taking Americans' hard earned money for junk plans that didn't pay anything when they needed well check ups for their kids, vaccines, pap smears, mamograms, basic care when sick with a cold, flu, pneumonia, asthma...I could go on.  Those plans were a big surprise when folks tried to use them to attain basic healthcare. They were deemed illegal by the ACA.

The ACA expanded medicaid in the states willing to accept the help to cover our working poor and children.

The ACA did NOT cause your insurance rates to go up!!  Insurance company execs did that...with the approval of state legislatures. Executives who make 15-20 million dollars a year for their amazing management skills.  THEY decided they needed even more....at our expense!!!

The ACA allowed children up to the age of 26 to stay on their family's plans.

The ACA is not perfect.  There are many ways in which it could be improved.  So why don't we??? Cause here's the deal...

HEALTH: AMERICA'S HUMAN INFRASTRUCTURE

The health of our nation, physical and mental, is the vital living human infrastructure of our society. That infrastructure is absolutely essential for everything else. It includes everyone from the infant to the elder. It encompasses all parts of life: birth, childhood, adulthood, old age and death. It is what and how we eat and drink. It is the air we breathe. Procreation, pain, suffering, joy and fulfillment are all rooted in our health. The health of our nation is sacred and shared. The health of one literally affects the health of all. Wisely, health is enshrined in our Declaration of Independence: Life, Liberty and the Pursuit of Happiness. It is life, that comes first as a necessary condition and the right to health care is the concrete embodiment of that right to life. There are those who are blind to the communal nature of health. They deny health care as a right, seeing it only as a privilege for the few with resources. A privilege restricted to those whom they consider innocent, powerful or wealthy enough to save from disease, suffering and death. We must fight for the right to our health care and our lives. All of us are innocent enough, powerful enough, rich and deserving enough to have the same opportunities for healthcare. So, we join the struggle for our health with the United States Congress. It is the struggle for and of our lives and those we love. It is also the struggle for the survival and spirit of the United States. We will not lose because we cannot lose.   (Just a little op-ed written by me and B)

Indeed, the health of our neighbors, friends and family - our fellow AMERICANS - is our most essential infrastructure.  The health of our nation is the well from which all else springs.

I believe in all Americans.  I believe that healthcare is a right ~ one that belongs to all of us ~ those is the prime of health with lots of money, as well as those who are less fortunate and perhaps more in need.  No matter where you fall on that scale today....it is a fluid place.  One minute you are gainfully employed with bountiful health, the next you are facing a life threatening illness, too ill to work (NOT too lazy!!!).  But, thanks to science and the generous spirit of your fellow Americans....you can cross the bridge to health and productivity once more.  YES, WE CAN do that for each other!  And....we should. 

Much love, les

Surprise, surprise, surprise! The sooner brain mets are found - the better folks with melanoma, breast cancer, etc...do!!!

Do you ever read a statistical study that involves bunches of patients, expert researchers, thousands of samples, statisticians and probably a significant chunk of change and think, "No shit, Sherlock!!!"? It happens to me all the time! ~ Just out!  New expert findings regarding obesity in children!  In this new research, utilizing multiple offices and institutions, patient and parental questionnaires, cox 2 data analysis, and all sorts of other jabber, jabber - We have found that obese children are more sedentary and consume more calories than their thinner peers!!!"

In that vein...there is this...

Toward the complete control of brain metastases using surveillance screening and stereotactic radiosurgery. Wolf, Kvint, Chachoua, Pavlick, et al. J Neurosurg. 2017 Feb 17.

The incidence of brain metastases is increasing with improved systemic therapies, many of which have a limited impact on intracranial disease. Stereotactic radiosurgery (SRS) is a first-line management option for brain metastases. The purpose of this study was to determine if there is a threshold tumor size below which local control (LC) rates approach 100%, and to relate these findings to the use of routine surveillance brain imaging.

From a prospective registry, 200 patients with 1237 brain metastases were identified who underwent SRS between December 2012 and May 2015. The median imaging follow-up duration was 7.9 months, and the median margin dose was 18 Gy. The maximal diameter and volume of tumors were measured. Histological analysis included 96 patients with non-small cell lung cancers (NSCLCs), 40 with melanoma, 35 with breast cancer, and 29 with other histologies.

Almost 50% of brain metastases were NSCLCs and commonly measured less than 6 mm in maximal diameter or 70 mm³ in volume. Thirty-three of 1237 tumors had local progression at a median of 8.8 months. The 1- and 2-year actuarial LC rates were 97% and 93%, respectively. LC of 100% was achieved for all intracranial metastases less than 100 mm³ in volume or 6 mm in diameter. Patients whose tumors at first SRS were less than 10 mm maximal diameter or a volume of 250 mm³ had improved overall survival.  

SRS can achieve LC rates approaching 100% for subcentimeter metastases. The earlier initial detection and prompt treatment of small intracranial metastases may prevent the development of neurological symptoms and the need for resection, and improve overall survival. To identify tumors when they are small, routine surveillance brain imaging should be considered as part of the standard of care for lung, breast, and melanoma metastases.

#1.  Well, duh.  If you find brain tumors when they are small and zap them out of existence, patients do not suffer as much damage and live longer.

#2.  I don't I agree with the opening salvo:  "The incidence of brain metastases is increasing with improved systemic therapies, many of which have a limited impact on intracranial disease."  At least in the sense that, as melanoma patients live longer, DUE to systemic therapies....we are seeing more of everything...cause these peeps are not dead!  Also, I fear that since we have learned that we can zap many, many brain tumors sequentially or simultaneously with SRS and melanoma patients actually respond positively as they did NOT when only whole brain radiation was offered or utilized, I fear that some docs are not being as aggressive as they should be in finding a systemic therapy that actually DOES work for the patient who is having brain met after brain met!!!
(Here's a recent post that supports my disbelief!!! - SRS with any systemic therapy helps response in melanoma brain mets...)

#3.  Instead of using this data as a published study to pad your researcher resume...my dear researchers!!!....use it to get insurance companies in line with paying for melanoma patients' brain imaging...instead of telling ANY melanoma patient, much less one status post BRAIN TUMORS - 

"You may experience the pleasure of your CT scans as planned, however in regard to the MRI...."Based on eviCore Oncology Imaging Guidelines, we are unable to approve the study your doctor requested.  Your records show that you have SKIN DISEASE that is stage 2B to stage 4.  Follow up magnetic resonance imaging, detailed picture study, of your brain is supported for this problem once per year for the first 5 years after your skin disease was found.  Your records do not show that this applies to you. This decision just means your health plan won't pay for the service.  You can still receive the service, but you will need to pay for it yourself.  {signed} Michele Awobuluyi, MD"   (This was the Blue Cross response to my onc's request for my now annual scans...you can check out the entire outrageous story here:  August 2016: And then there's me...)

Researchers, you have the data, the reputation, the expertise, and the clout to put the pressure on insurance companies to provide the care that your patients need.  Do it!!!!

#4.  And since this is one more perfect opportunity to say it, "Michele Awobuluyi, MD, NYU alum - you are an ass and an idiot, a disgrace to your profession and a danger to society."  I hope you google your own name!!!

Being a rattie is tiring!  Hang tough, ratties.  Hang tough. - c

PV-10 followed by radiation = ORR of 86% in in-transit, dermal and sub q melanoma

I have been yelling about intralesionals and Rose Bengal (PV-10) for YEARS!!!!!!!!!!!!!

Here's a review:
2016: Intralesional Therapy....and patterns of response from the T-VEC OPTiM trial
2016: Intralesional PV-10 (Rose Bengal, y'all!!!) positive treatment for in-transit melanoma
ASCO 2016: New studies! Rose Bengal and Pembro for Stage IV y'all!!! Enrolling! For Stage IIIb/c: PV-10 vs T-VEC.
2016: Study on Intralesional Rose Bengal out of Moffitt...we know a bit more about HOW it works!!!
2016: CAVATAK - intralesional therapy derived from the coxsackievirus
And finally, this one...with 3 links to additional reports from 2014, 2013, and 2012, and2014: More info from ASCO....PV-10...Rose Bengal for melanoma....

Now, there is this......

Results of a phase II, open-label, non-comparative study of intralesional PV-10 followed by radiotherapy for the treatment of in-transit or metastatic melanoma. Foote, Read, Thomas, et al. J Surg Oncol. 2017 Feb 23.

In-transit and recurrent dermal or subcutaneous melanoma metastases represent a significant burden of advanced disease. Intralesional Rose Bengal can elicit tumor selective ablation and a T-cell mediated abscopal effect in untreated lesions. A subset of patients in a phase II trial setting received external beam radiotherapy to their recurrent lesions with complete or partial response and no significant acute radiation reaction.

An open-label, single-arm phase II study was performed to assess the efficacy and safety of PV-10 followed by hypofractionated radiotherapy. Patients had in-transit melanoma metastases suitable for IL therapy and radiotherapy.

Fifteen patients were enrolled and thirteen completed both treatment components. The overall response rate was 86.6% and the clinical benefit was 93.3% on an intention to treat analysis. The median follow up duration was 19.25 months. Size of metastases (less than10 mm) predicted lesion complete response (74.6%). Treatment was well tolerated with no associated grade 4 or 5 adverse events.  

The combination of PV-10 and radiotherapy resulted in lesion-specific, normal tissue-sparing, ablation of disease with minimal local or systemic adverse effects.

Small numbers of patients, but the results - "Not bad, not at all bad!!!" - c

Sew Chaotically! - Rumi Dress by Christine Haynes

I loved this dress (and top) the minute I saw it on various sewing blogs I was spying on!!!!  And now that I've made it, I love it even more!!!!

The fabric is a BLUE waffle knit I ordered from Mood sometime ago.  It washes and dries beautifully and has the perfect drape for this dress.  I used some bits of it in this Linden sweatshirt!!!

Having used those bits in the Linden, I was a little short in being able to cut the hem band for the dress as the pattern directs and instead just cut the dress to the size 18 length.  Initially, I cut the size 10 in all other dimensions, but ended up taking the shoulder straps down to a two (so the neck line didn't fall below my boobers!!) and the sides to a 6 at the bust graduating back to the 10 at the sides.  I did sew in some stabilizing tape to the shoulder seam to help prevent that seam from stretching.

The neck and arm bindings go on like a dream.  I just cut those pattern pieces down to match the size I settled on in those areas.  

I sewed the bindings in place using my sewing machine, then serged them, and finished them off with a zig zag stitch on my sewing machine. I serged the bottom edge of the hem, applied knit stay tape to give a little support and a clean edge when I folded the hem up, and zig zagged that in place as well.

This has been such a fun and rewarding sewing project.  Now the weather just needs to warm up so I can whirl around in my cute dress!!!  Sew Chaotically! - les

COX-2 expression correlates with PD-L1 expression on melanoma cells - or....how NSAID's like aspirin and advil might help melanoma patients????

COX-2 expression in melanoma cells is what has given the hope (??? data) that the use of NSAID's (advil, aspirin, etc) might enhance the response from immunotherapy in melanoma patients as noted in this post (with links to others within):  Sooo....advil works for SOME melanoma patients?????

COX-2 expression positively correlates with PD-L1 expression in human melanoma cells. Botti, Fratangelo, Cerrone, et al. J Transl Med. 2017 Feb 23.

The resistance to PD-1/PD-L1 inhibitors for the treatment of melanoma have prompted investigators to implement novel clinical trials which combine immunotherapy with different treatment modalities. Moreover is also important to investigate the mechanisms which regulate the dynamic expression of PD-L1 on tumor cells and PD-1 on T cells in order to identify predictive biomarkers of response. COX-2 is currently investigated as a major player of tumor progression in several type of malignancies including melanoma. In the present study we investigated the potential relationship between COX-2 and PD-L1 expression in melanoma.

Tumor samples obtained from primary melanoma lesions and not matched lymph node metastases were analyzed for both PD-L1 and COX-2 expression by IHC analysis. Status of BRAF and NRAS mutations was analyzed by sequencing and PCR. Co-localization of PD-L1 and COX-2 expression was analyzed by double fluorescence staining. Lastly the BRAF^V600E A375 and NRAS^Q61R SK-MEL-2 melanoma cell lines were used to evaluate the effect of COX-2 inhibition by celecoxib on expression of PD-L1 in vitro.

BRAF^V600E/V600K and NRAS^Q61R/Q61L were detected in 57.8 and 8.9% of the metastatic lesions, and in 65.9 and 6.8% of the primary tumors, respectively. PD-L1 and COX-2 expression were heterogeneously expressed in both primary melanoma lesions and not matched lymph node metastases. A significantly lower number of PD-L1 negative lesions was found in primary tumors as compared to not matched metastatic lesions. COX-2 expression significantly correlated with PD-L1 expression in both primary and not matched metastatic lesions. Furthermore, in melanoma tumors, cancer cells expressing a higher levels of COX-2 also co-expressed a higher level of PD-L1. Lastly, inhibition of COX-2 activity by celecoxib down-regulated the expression of PD-L1 in both BRAF^V600E A375 and NRAS^Q61R SK-MEL-2 melanoma cell lines.  

COX-2 expression correlates with and modulates PD-L1 expression in melanoma cells. These findings have clinical relevance since they provide a rationale to implement novel clinical trials to test COX-2 inhibition as a potential treatment to prevent melanoma progression and immune evasion as well as to enhance the anti-tumor activity of PD-1/PD-L1 based immunotherapy for the treatment of melanoma patients with or without BRAF/NRAS mutations.

Breaking it down:  This report supports the notion that there is a relationship between COX-2 and PD-L1 expression in melanoma. Therefore, if we could block COX-2 we would reduce PD-L1 expression in melanoma cells and make anti-PD-1 drugs more effective. That's the theory anyway!!   - c

Chaotic Cookery! - From Someone Else's Table: Broccoli Lemon Soup

This recipe was inspired by one I saw from Food 52.  While I love a thick cheesy broccoli soup, this lighter version with the tang of lemon is really perfect.  On this chilly day with our second snow in the past few days...while harboring hopes for spring...this fresh, but warming soup is just what the doctor ordered!

Broccoli Lemon Soup

1 clump broccoli - in my world stores usually package 2 - 3 stalks together
3 cloves garlic, minced     3 T olive oil      s/p to taste
6 c chicken broth     1 c Parmesan, grated       1-2 lemons

Saute garlic in oil until tender and oil is flavored.  Add broccoli, including stalks chopped up with tough bits removed.  Toss broccoli around and simmer on low, covered, until broccoli is tender, about 10-15 minutes.  Take out pretty florets when they are just bite tender and set aside.  Add stock and simmer about 15 minutes.  Let cool.  Puree.  Add lemon juice and parm.  Bring back to simmer and toss in reserved florets.  Serve with crusty bread and a salad for a great veggie meal.

So good!!  Enjoy your dinner From Someone Else's Table! - c

The whole she-bang - immunotherapy WITH BRAF/MEK for melanoma...

I posted this in November:  BRAF/MEK combined with immunotherapy!!!

Now there is this:

Targeting the MAPK and PI3K pathways in combination with PD1 blockade in melanoma.  Deken, Gadiot, Jordanova, et al.  Oncoimmunology. 2016 Oct 14.

Immunotherapy of advanced melanoma with CTLA-4 or PD-1/PD-L1 checkpoint blockade induces in a proportion of patients long durable responses. In contrast, targeting the MAPK-pathway by selective BRAF and MEK inhibitors induces high response rates, but most patients relapse. Combining targeted therapy with immunotherapy is proposed to improve the long-term outcomes of patients. Preclinical data endorsing this hypothesis are accumulating. Inhibition of the PI3K-Akt-mTOR pathway may be a promising treatment option to overcome resistance to MAPK inhibition and for additional combination with immunotherapy. We therefore evaluated to which extent dual targeting of the MAPK and PI3K-Akt-mTOR pathways affects tumor immune infiltrates and whether it synergizes with PD-1 checkpoint blockade in a BRAF^V600E/PTEN^-/--driven melanoma mouse model. Short-term dual BRAF + MEK inhibition enhanced tumor immune infiltration and improved tumor control when combined with PD-1 blockade in a CD8⁺ T cell dependent manner. Additional PI3K inhibition did not impair tumor control or immune cell infiltration and functionality. Analysis of on-treatment samples from melanoma patients treated with BRAF or BRAF + MEK inhibitors indicates that inhibitor-mediated T cell infiltration occurred in all patients early after treatment initiation but was less frequent found in on-treatment biopsies beyond day 15. Our findings provide a rationale for clinical testing of short-term BRAF + MEK inhibition in combination with immune checkpoint blockade, currently implemented at our institutes. Additional PI3K inhibition could be an option for BRAF + MEK inhibitor resistant patients that receive targeted therapy in combination with immune checkpoint blockade.

Granted this is in real live mousies....but when BRAF/MEK was given with anti-PD-1.... T cell infiltration of the tumor was facilitated early on...but not so much after 15 days. So....maybe the full barrage of the combo early....could actually benefit human ratties!!

Thanks to the mousies...and hang tough, ratties! - c

PS  It was tough...but we survived our recent blizzard:

Hope all my more northern peeps have their fur panties and snow boots at the ready!! Y'all stay safe and warm, now.... you hear???? - les

Stupid Cancer - With a smile and a bit of hope

My kids gave me this bag when I graduated from UAB years ago.  It has traveled room to room in my office as I have cared for my little charges and their families.  My first experience with melanoma occurred while working on that degree, but all the rest has been dealt with while employed at my current office. As you can see, my bag has been embellished along the way.

Clearly, my bosses/coworkers and dear nursing peeps have always been fully aware of my diagnosis and treatment.  I've never been secretive about much of anything when it comes to me!!! (Despite that, or maybe because of it, ????, I am a very good secret keeper for others!!!) Some families are aware of my diagnosis....I mean, I work in a small town in the south!!!!  But, I don't routinely share personal details with my patients.  Their visits are about them!!!!!  Not me. Besides, when you've been a melanoma "patient" for over 13 years - especially in a pediatric office - it's old news!

Still, I've always taught parents, and actively embraced, truthfulness in response to children's questions. Whether they ask about sex, politics, why the grass is green, or what's for dinner, I think it is best to answer them directly, with as little or as much information as they are interested in or are capable of comprehending - and sometimes, that's a lot!

Given to me by a dear friend and nursing peep whose mom was diagnosed with cancer the same year I progressed to Stage IV, my "Stupid Cancer" button has engendered more comments from my little people than I ever expected.  In the middle of many exams, they'll say very quietly, "I think cancer is stupid, too." I reply, "Me, too! Why do you think so?"  This has been an amazing opener that has given many an opportunity to tell me about the sorrow, confusion, anger - they are experiencing while dealing with a cancer diagnosis or death of their beloved uncle, granny, friend... Struggles I would probably know nothing about without the nitus of the button.

But, when dealing with kids, simple questions can sometimes take an unexpected turn.  Last week an incredibly bright little girl, aged 8, toward the end of her physical asked, "Why do you have that cancer, uhhhh, isn't nice, thing on your bag?"  Clearly, she had been taught that calling something 'stupid' wasn't a polite thing to do!!!  "Because that's how I feel about cancer," I replied.  "Me, too!" her mom exclaimed.  "But, why?" the little girl continued. "Well, cancer hurts some folks, so I don't much like it." I shared.  The minute I saw the look on her face, I knew that was not going to be a satisfactory end of the story for her!

"But...." with a serious, you can do better than that....look!!!

"Well," I told her, "I had cancer."  The light of understanding dawned!

She smiled at me sweetly. "Oh!  So that's why your hair is so short!!!!!!!!"

I burst out laughing, as her mother looked mortified. "No, that's just a personal choice.  But, that's really good reasoning, considering!!!"

She smiled again, "I like how you have it!"

#brightkids  #stupidcancer   #reasonIlovemyjob  - les

And....a hopeful video that discusses cancer generally with some melanoma specifics:  Charlie Rose presentation of cancer and its hopeful trends and treatments

Sew Chaotically! - Colette's Redemption in the Sorbetto Top!

You may remember that I had fun making a few spring tops for, Roo (To see the pic, click here!) After paying full price for the Colette Aster (The Aster Disaster!!!) pattern....I got the Sorbetto pattern for free.  And you can too!! Just check out this link:  Colette Patterns - Sorbetto Tank Top

Bentie was a sweetie, printing and putting the pattern together for me!!

I made this one first to test the size and such!   It was made with scraps of material used long ago in a simple play dress I wore chasing the kids around when they were small.  Given the material, it is a little hard to see the front center pleat.  My only pattern change for all the tops was to raise the neckline in the back. When worn with a pink sweater as my Valentine's Day attire, it got lots of compliments from my peeps!

I wanted to use this bit of material for Roo, since I had made her shorts and a cute sundress with it when she was little and it was a favorite!  The kind that was put on as soon as it was out of the wash!!  Given the limited yardage that remained, I had to omit the front pleat.  But this pattern is so versatile...you can do that!!!

Now, how cute is that???

I purchased this crazy print with Rose in mind from Hancock's (back when that store existed)!  And it seemed perfect for a little Sorbetto!!  

This top begs for cute variations.  I kept the bias tape finish, sight unseen in my version.  In her butterfly one, I let it shine.   Here, I made it as funky as possible, not only exposing it, but highlighting it, with contrasting thread.

Finally,  I made myself this one out of scraps from a dress I had made, since it matched this cute skirt Ruthie gave me for Christmas soooo perfectly!  Already wore it to work with a little black jacket, but it will be great for summer on its own.

Had to piece the back, given my limited yardage...but you can do that with this pattern!!!  No problem!!

Colette certainly redeemed itself here.  Free and FABULOUS!! I can see myself making many more of these little tops.  Eyelet with a scalloped hem.  Another out of a silky, flowing fabric. Linen....

#colettesorbetto    Sew Chaotically!!! - love, c

What to do in melanoma after anti-PD1 fails or upon regression after a response?

In melanoma world we are lucky to have anti-PD-1 and its 40% response rate.  However, as more of us have taken it, and failed...or even responded...but progressed later....the pressing question becomes...   Now what??????

Here are some articles that attempt to answer...

There was this (with a couple of links within):  ASCO 2016 - Other therapies after failing Pembro...and...trial with OX40 - alone and with Pembro...still enrolling...

And this:  Response to ipi or ipi/nivo after failing anti-PD1 as single agent in Stage IV melanoma

Now there is this case study...

Reinduction of PD1-inhibitor therapy: first experience in eight patients with metastatic melanoma. Blasig, Bender, Hassel, et al. Melanoma Res. 2017 Mar 2.

Significant progress has been made in the treatment of metastatic melanoma during the last years. Approval of immune-checkpoint inhibitors and targeted therapies has been achieved recently. The sequencing of these therapies is an important issue. Here, we report our experience with the treatment and retreatment with PD1-inhibitors (PD1i) in eight patients. The patients (two female and seven male with a median age of 70 years, all melanoma stage IV, M1c) underwent a first treatment period with PD1i for a median of 5.5 months. Three (37.5%) patients had a stable disease as best response, two (25%) showed progression, two (25%) showed partial response, and one (12.5%) achieved complete remission. PD1i was discontinued due to disease progression in seven patients and due to side effects (pancreatitis) in one patient. Patients were subsequently treated with ipilimumab (n=2), or chemotherapy (n=4), or no other medical treatment (n=2). All eight patients were subsequently retreated with PD1i for a median of 2.5 months. One (12.5%) developed a partial response, whereas in three patients (37.5%) the disease was stabilized. PD1i have shown a high and durable response rate in the first-line treatment of metastatic melanoma. Our study suggests PD1i retreatment as a reasonable option for selected patients. Further investigations are needed to verify the value of PD1i re-exposure and to identify subgroups of patients who can benefit.

Well, that's something.  But, too many of us need more!!!  Hang in there ratties!! - c

Super Cool? Or kinda sad?????

After a busy day at work and answering a couple of emails from some of my melanoma peeps, I opened another email to find the link below:

Top 70 Melanoma Blogs For People Living With Melanoma Disease

As determined by Feedspot.com, with this caption:

Top 70 Melanoma Blogs Winners

CONGRATULATIONS to every blogger that has made to Top Melanoma blogs list! This is the most comprehensive list of best Melanoma blogs on the internet and I’m honoured to have you as part of this! I personally give you a high-five and want to thank you for your contribution to this world.

So, yeah.  I'm number 22.  Which does make me kinda proud.  (Even though I can't help but notice the typo/poorly written first sentence in their blurb!!)  But, also a bit sad to realize that the folks battling this disease need this much advocacy...knowing that there are many more than these 70 blogs out there! On the other, hand, with all this cheering and yelling and participation....surely, together, ratties and researchers alike, will make the world a better place for those dealing with melanoma...until no one need talk, nor write, nor deal with melanoma, ever, ever never!!!! Amen.

But, if you are in need of answers, help, or camaraderie ~ take a look at the list and check out some good peeps with lots of info that you might find helpful to you and yours.  It takes a village.  love, c

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!

Back when the world was young (2010 or so) and ipi (in other words, immunotherapy period) was finally producing positive responses for folks with melanoma, we simultaneously learned of the negative effects that could be wrought on the poor patient's immune system and really feared what could possibly happen if you were treated with immunotherapy when you KNEW that you already had an existing autoimmune disease process like asthma, colitis, or arthritis.  The solution by pharma and researchers? Exclusion from treatment!!!  By 2014, with this still unsolved conundrum hanging in the air, we certainly didn't know what to do with folks who developed immune related side effects to ipi, but still needed treatment for melanoma.  Could they be treated with the two newer immunotherapy drugs, anti-PD-1 products Nivo (Opdivo) or Pembro (Keytruda)?  No!  Exclusion from treatment remained the norm...as you can see in this post!!  (Yes, children.  Folks talked pretty funny back then, calling Keytruda, first MK-3475, then Lambrolizumab, then Pembrolizumab! Crazy things happen when the world is new!!)

Anyhow - here's the link:

Program for MK-3475 in Participants With Metastatic Melanoma Who Have Failed Standard of Care Therapy Including Ipilimumab (MK-3475-030)  which says in part, with my response:
Exclusions include - "history of life-threatening or severe immune-related adverse event" on prior immunotherapy.   Who decides?  Is an admission for colitis on ipi, though now recovered, considered a "severe immune-related adverse event"?  Is ipi induced hypothyroidism?

As things moved along...there was this:  April 2016: Anti-PD1 success in melanoma despite prexisting autoimmune disease, a case report

And this from ASCO (See the first abstract):  ASCO 2016 - Three anti-PD-1 reports

Now, there's this:

Programmed cell death protein-1 (PD-1) inhibitor therapy in patients with advanced melanoma and preexisting autoimmunity or ipilimumab-triggered autoimmunity. Gutzmer, Koop, Meier, et al. Eur J Cancer. 2017 Feb 16.

Programmed cell death protein 1 (PD-1) inhibitors are a common treatment strategy for metastatic melanoma and other tumour entities. Clinical trials usually exclude patients with preexisting autoimmune diseases, thus experience with PD-1 inhibitor (PD-1i) in this patient population is limited.

Metastatic melanoma patients with preexisting autoimmune disorders or previous ipilimumab-triggered immune-related adverse events (irAE) undergoing treatment with PD-1i from seven German skin cancer centres were evaluated retrospectively with regard to flare of the preexisting autoimmunity and development of new, not preexisting irAE as well as response to PD-1i therapy.

In total, 41 patients had either preexisting autoimmunity (n=19, group A, including two patients with additional ipilimumab-triggered autoimmune colitis) or ipilimumab-triggered irAE (n=22, group B). At PD-1i therapy initiation, six patients in group A and two patients in group B required immunosuppressive therapy. In group A, a flare of preexisting autoimmune disorders was seen in 42% of patients, new irAE in 16%. In group B, 4.5% of patients showed a flare of ipilimumab-triggered irAE and 23% new irAE. All flares of preexisting autoimmune disorders or irAE were managed by immunosuppressive and/or symptomatic therapy and did not require termination of PD-1i therapy. tumour responses (32% in group A and 45% in group B) were unrelated to occurrence of autoimmunity.

While preexisting autoimmunity commonly showed a flare during PD-1i therapy, a flare of ipilimumab-triggered irAE was rare. Response rates were above 30% and unrelated to irAE. PD-1i therapy can be considered in patients with autoimmune disorders depending on severity and activity of autoimmunity.

So....while caution and careful monitoring is certainly warranted...these peeps with an inherent pre-existing autoimmune process or one gained from having taken ipi....were successfully managed with "immunosuppressive therapy", "did not require termination of anti-PD-1 therapy", AND gained responses at a rate of 32-45%!!!!!!!!!!!!!!

ONE MORE TIME! Folks with immune disease took anti-PD-1, took prednisone or other immunosuppressive treatment to manage flares, did NOT have to stop anti-PD-1 therapy, and many DID gain a response!  

Could all you oncologists out there read and repeat??  Folks with auto-immune conditions CAN take immunotherapy with careful monitoring. Auto-immune flares SHOULD be treated with immunosuppressive therapy while on immunotherapy.  AND these patients can STILL.....GAIN A RESPONSE!  

And in case that still isn't clear enough...  What happens to folks with recurrent Stage IV melanoma who aren't effectively treated????  There ain't no Stage V people!

Okay, I'll quit yelling.  For now. - c