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August 27, 2014 at 2:51 am #22153
I’m the lead online researcher for Team Matt, and just found your excellent site. I was hoping you could help as we try to figure out our strategy. I know there’s a separate board for newly diagnosed patients, but this one seems far better traveled. I apologize.
My brother, Matt, was diagnosed about two weeks ago with Stage IV melanoma. He’s 43 years old and the father of three boys (10, 12 and 14). He noticed a lump under his left shoulder several weeks ago, had it biopsied, and then had full scans and blood work at IU Mel and Bren Simon Cancer Center here in Indianapolis. Oncologist Dr. Ted Logan noted the tumor under the left shoulder, metastasis with minor bone involvement on right shoulder, some presence in adrenal glands and stomach, and small areas in lung and liver. BRAF negative. Dr. Logan ran through several possible therapies (principally, IL-2, or ipilimumab, or perhaps an ipi/nivo trial if available) and then went on a previously scheduled vacation. That has given us time to do research, which has been illuminating and also frustrating.
We got lucky and had a connection with MD Anderson, so Matt has an appointment Wednesday (8/27) to see Dr. Patrick Hwu, who has all the previous material. So we’ll see what he has to say. Follow-up appointment with Logan is next week.
A few pressing questions:
1) Team Matt is divided on how quickly he should get treatment. Some think he should have SOME sort of treatment (probably IL-2) as quickly as possible, realizing that it’s just a first line and that other treatments probably will follow. The other folks have read about patients who took as long as 7 weeks to do their research and to vet doctors and therapies and facilities. Does anyone have a sense of whether one approach (quick treatment vs. more thorough research) is better than the other?
2) We’re aware via clinicaltrials.gov of the hundreds of clinical trials that are being conducted for Stage IV melanoma, and the dozen or so that Matt probably would be eligible for and are currently recruiting. Logan’s staff, which has been incredibly positive and supportive, offered to take the lead in contacting trial providers and facilities. However, we so far have heard very little on this front. Should we be actively contacting the administrators of the trials ourselves and taking the lead on that?
3) Just in general, does anybody have any thoughts they’d like to share about Logan or Hwu?
4) Does anybody know for sure if there is an ipi/nivo (concurrent) trial currently open, or otherwise taking patients?
Sorry for the long message. We’re just at the beginning of this, and it seems overwhelming right now. Anything you can contribute would be very appreciated. Thanks so much!August 27, 2014 at 4:40 am #65310RJoeyBParticipant
I can relate to where you’re at right now and was in a very similar situation when I was diagnosed at Stage IV in the summer of 2010 — I was 39 then and am now 43 like your brother. I also had some good help around me, my local oncologists were helpful in providing local options in Philadelphia but also connecting us with other trial options, and one of my younger brothers (an orthopedic surgeon) was helpful in researching those options and also had a connection to a connection to someone well-known in the melanoma field. I won’t detail all the twists and turns my journey has taken, but I ultimately started in a trial where I first received IL-2, had disease progression, then had TIL, had a good but not complete response, and have since had 7 surgeries, 6 rounds of radiation, and received ipi. I’m not currently NED, but have been close, and I strangely say I’m fortunate in that my disease has been slowed enough by the treatments I’ve received that we’ve bee able to handle several metastases, including a brain met, one at a time with conventional treatments. I’ll qualify all of that by saying that at the time of my diagnosis, ipi wasn’t yet approved, nivo and pembro weren’t much more than a blip on the radar, and although I tested BRAF positive, the BRAF inhibitors also weren’t approved and even a leading BRAF advocate told me that if I could get into a TIL trial at NIH (more on that in a minute) where I had already consulted, that it would be my best option. I had a lower tumor burden than your brother — a primary on my back, at least one node in my underarm, and a bone met in my shoulder bone. To respond to your first question, though, we did take our time researching options, making connections, having appointments to understand our options, and make our decision. From the time I was staged at IV through all the consultations including my intake and workup at NIH, it was almost 6 weeks before I began any actual treatment at NIH, including the removal of the primary lesion on my back.
Some food for thought as far as IL-2, you’ll find varying opinions about it here – I just finished posting something over on MPIP about it. Some doctors are quickly moving away from it while others still see it as an option. I think it’s a very personal decision and here’s (mostly) a copy and paste from what I wrote on MPIP about what I think is the reasoning being used for/against IL-2 as a first-line option (this was written in response to someone who is considering ipi or nivo or an ipi/nivo combo, but had a doctor also mention IL-2):
“I think some respected doctors and institutions continue to see IL-2 as an option for a subset of patients at opposite ends of the spectrum. For those who have tried and failed every other option, IL -2 may be seen as a last ditch resort, but unfortunately, many of those patients are too sick to withstand the treatment. The other group is what I guess what I’d call early Stage IV — along with low tumor burden that doesn’t seem to be acting all that aggressive and in an otherwise healthy patient, i.e. able to better withstand the treatment. Despite the low response rate as compared to ipi and now nivo/pembro, it’s one of those things that when it works, the response can be very, very durable (long-lasting). It can come down to a patient’s mindset and risk profile — some people, especially with slow-moving disease and knowing that there are other options available if IL-2 fails are willing to take that proverbial swing at achieving a long-term response with IL-2. I did IL-2 in 2010 and my reasons were more related to the trial I was in, but I understand how that approach could be appealing to some folks and at least worth a discussion with the doctors. What we’ll learn over the next few years may change all this, as longer-term data about durability of responses for the checkpoint inhibitors like ipi, nivo, and pembro continues to come in — they may very well prove to have durability as good or better than IL-2. The data today already shows a statistical “long tail” for many patients who have responded to ipi and I suspect that long tail is rapidly building for PD-1, too. IL-2 just has a huge head start in data having started trials In the 80’s and receiving FDA approval for melanoma in 1998.
As I said, I did IL-2 in late 2010. Ipi was still in trials and didn’t receive FDA approval until 6 months after I finished IL-2. It was tough but I was in that “otherwise healthy” category and the side effects resolved quickly following treatment (within hours to days for the worst side effects and weeks for the less severe, nothing long-lasting). Unfortunately, I had disease progression after my first two cycles and had the opportunity to switch over to the TIL arm of the trial I was in, but if I had to do IL-2 again, I would. Despite the progression, IL-2 may still have played a role in slowing things down, too. However, given the data we already have about ipi, nivo, and pembro, today, I think I’d lean towards one of them (or a combination) vs. IL-2 as I’ve already stated. But I understand the mindset that might want to try IL-2 first under the right circumstances.”
Back to your next question, I think it is incredibly helpful to have the active involvement of your doctors in contacting the trial coordinators and leveraging any connections they have. They certainly need to be responsive to requests for copies of necessary scans and reports, but hopefully they can be opening doors to trials more quickly than you can do on your own.
I don’t know anything about Dr. Logan, but IU also has a great melanoma resource in Dr. Schwartzentruber, who not only is the medical director of IU’s cancer services, but is well-known in melanoma circles and accepts new patients. Around the time I was diagnosed, he had been recently named to the Time Magazine 100 Most Influential People for his work with cancer vaccines. My understanding is that he spent a fair portion of his career at NIH/NCI in Bethesda before returning home to Indiana, and during our early research, we were fortunate to be able to get some advice from him. So given that he and Dr. Logan practice at the same facility, you may be able to consult with Dr. Schwartzentruber. And he likely knows Dr. Hwu personally, as Dr. Hwu also spent part of his career as a fellow and researcher at NCI/NIH before moving to MDA. I think their time there overlapped and they were on the same staff, perhaps in the late 90’s or early 2000’s. You didn’t mention TIL, or Tumor Infiltrating Lymphocytes, in your post, but I imagine Dr. Hwu will — I think he leads the TIL program at MDA. I’ll let you start to research TIL on your own and am happy to answer questions about it, having gone through it, but for now, know that it has its origins at NIH under Dr. Steven Rosenberg, and both Drs. Hwu and Schwartzentruber worked directly for Dr. Rosenberg and are therefore very familiar with TIL.
Ipi and/or nivo (or pembro) are great options and probably the likely path your brother will start with, I’m sure Catherine can help connect you with trials. Again, when your brother sees Dr. Hwu, I expect that TIL will also be discussed, so just be prepared to be offered it as an option. There are varying opinions on TIL that you can read here and elsewhere, and with the approvals of ipi and BRAF inhibitors in 2011, plus the pending approvals of pembro and then nivo, the landscape has changed quickly. It’s a complicated discussion and the varying opinions are fair, I understand and appreciate both sides. In a nutshell, parts of TIL treatment can be difficult (it includes a round of IL-2, among other things), and compared to the newer treatments, not a lot of patients have received it, but response rates are high and often durable (some will caveat that some of the sickest patients are unable to receive it and excluded making the response rates seem higher). But again, just be prepared to hear more about it and consider it as you’re looking at options, if not now then as a possible option later if needed. It requires the “harvest” of a tumor to grow the TIL cells, and I know MDA is also currently offering an option to harvest and “bank” a tumor now for use later, even if you’re considering other treatments before. So before starting any other treatments, it’s just good to know this upfront. Right now, TIL is only offered at three locations in the U.S.: NIH/NCI in Bethesda, MDA in Houston, and Moffitt in Tampa. In the past couple of days, I’ve also seen a couple short news articles about it being a “new” procedure being offered at Loyola in Chicago, but I don’t know much about it. It’s not “new”, there have been variations of it offered at NIH for 10+ years.
I hope that helps. Wishing you and Team Matt the best as you explore options and move towards a decision with your brother.
JoeAugust 27, 2014 at 11:48 am #65311
Happy to help your team and you can also call our helpline or email me personally for personalized help and guidance.
The most promising route to remission right now according to the research and large oncology meeting called ASCO is: get Pembro (the PD1 by Merck) It has the highest response rate of all therapies and durable response. But, it looks like it will require taking IPI first. So I would recommend he start the IPI asap and then be able to move onto Pembro when it is approved hopefully in the next two months.
IL2 is an old drug that 94% of folks do NOT get a response to. It is highly toxic and may impair the immune system.
We’re here to help!August 27, 2014 at 7:24 pm #65312MathewRParticipant
I’m sorry to hear about Matt’s situation. The initial period following diagnosis (while selecting an initial treatment) is very tough psychologically, emotionally, etc. You are providing a great service in helping Matt get acclimated to his new life. That said, my number one suggestion for Matt (right after seeing a leading melanoma specialist, which he is doing in seeing Hwu) is that he become his own lead researcher. Hopefully, Stage IV will be a marathon and not a sprint for Matt. There is so much jargon that he needs to become familiar with in order to make educated choices, recognize side effects, etc. Wishing Matt strength and good judgment during this challenging time.August 28, 2014 at 2:32 am #65313 Joe, Catherine and Mathew, thanks so much for your input! I’ll find out tomorrow what Hwu recommended. In addition, I understand there is a trial opening next month at Sloan-Kettering that Matt would be a good candidate for, so that’s probably the next stop.August 28, 2014 at 2:03 pm #65314AnonymousGuest TM, MSK has, I believe the IPI/NIVO combo trial still available. The early results for that trial are very encouraging indeed, with response rates approaching 50%. The same trial is available at Yale. I’m not sure if BMS is oppenning this up for expanded access yet. There are higher grade side effects than either agent alone, but they have been managed well by the study teams. So, if you’re in contact with MSK and there are slots available, you may want to check that out too.
JeffAugust 28, 2014 at 4:15 pm #65315
The Ipi/NIVO is in EAP, but I don’t have locations, and the locations for NIVO eap are hard to find. Will continue my search. I think that the combo is promising, but also pretty high in toxicity. The results were only in a small group of patients as well. The Merck Pd1 looks to be approved ahead of schedule, a lot of buzz about this, maybe September!
I did find the following nivo/Ipi combo recruiting:
http://clinicaltrials.gov/show/NCT01621490August 29, 2014 at 12:57 am #65316BNP68Participant Catherine,
When Pembro does get approved will it be able to be used as a first line of defense or will you still have to have failed Ipi and braf (if braf Positive)?
BrianAugust 29, 2014 at 12:02 pm #65317
Sadly, it looks like you will have to fail IPI first. Looks like the braf therapy won’t be required. But I do believe doctors will be able to work around this as insurance companies are bound to be an issue for those who want the therapy to be first line.September 1, 2014 at 2:06 am #65318 Hey folks, just a quick update on Matt’s trip to MD Anderson. He and our parents came away with a very positive impression of Dr. Patrick Hwu (and all of the staff). They’re sold on a multi-phase therapy that goes something like: harvest cells from a tumor under his left shoulder for later use; then Yervoy combined with a biochemo regimen consisting of IL-2, interferon, cisplatin, and temozolomide; then pembro; then infusions of TIL bathed in IL-2. I understand that if he shows great improvement along the way, some steps might not be necessary.
Surgery to get the cells would be Sept. 9, and then there apparently is a waiting period to make sure the body has healed from the surgery before he can start IL-2/Yervoy.
Does anybody know about how long that takes?
Any thoughts about this treatment regimen? We’re told that this kitchen-sink mix of treatments results in at least 50-percent survival rate over 5-10 years.
There still might be a trip to Sloan-Kettering in hopes of speaking with someone (hopefully Jedd Wolchok) about the ipi/nivo trial, but Matt is moving as quickly as possible with MD Anderson as the primary option.
We’re a little taken aback by how quickly Matt gets tired now. About three weeks ago, he played 18 holes of golf in 85-degree weather (and won a local doubles tournament). Today, he says 18 holes in 65-degree weather wouldn’t be possible. His shoulder with the met also is quite a bit more painful. This is new to us, so it seems very scary. Maybe this isn’t a big deal, relatively speaking, for Stage IV patients. I know the progression of the disease is different for everybody; I’m just hoping that he has a window to get in for the first treatment and still be in decent health. He still seems in very good spirits, though!
Joey, thanks again for your very detailed message on your experience, IL-2, etc. Matt and our folks actually were reading it in the waiting room before they went in to see Hwu, and having that info was very helpful to them.
Thanks again, everyone!September 1, 2014 at 11:27 am #65319
The TIL therapy suggested has a lot of unknowns. It has never been tried against the newer less toxic therapies. The only good stats on it are from NCI which MDA can’t replicate. Our scientific advisory chair, melanoma expert at Mass General, Dr. Keith Flaherty notes: “the balance of efficacy and safety has not been sufficiently established for TIL therapy to know how to consider it as an option in relation to ipilimumab, PD 1/PD L1 and BRAF inhibitor-based therapy. And, randomized trials are certainly lacking. In the past, it was unclear if TIL therapy would ever be brought forward for consideration by the regulatory therapies as an approved. But, that has changed in the past year as several new biotech companies have been formed around the concept of developing T cell therapy as a treatment approach that can be presented to regulatory authorities for potential approval. Still a long way to go, but at least the type of rigorous data needed to judge its merits may come in the near future. One major issue that will always be a factor is that patients have been very carefully selected for TIL protocols to date and that makes it very hard to understand if it could ever be generally relevant to the majority of melanoma patients.”
You also might want to read the blog of Patient Number 1, who tried this therapy, and recurred. He’s now on PD1.
http://www.philly.com/philly/blogs/patient1/September 4, 2014 at 3:12 pm #65320RJoeyBParticipant Team Matt,
I’m glad some of the information I shared last time was helpful, sorry it’s taken a few days to get post back to your latest update. If I understand correctly, it sounds like Dr. Hwu and MDA have mapped out a long-term strategy for you, with not just a plan A but also plans B and C if Matt has disease progression, with TIL actually being plan C, but harvesting the tumor upfront so it’s available if needed — that’s what I was alluding to in my original response to you. A few thoughts:
I’m not familiar with any protocols combining ipilimumab with biochemo, but did a search and found a trial on ClinicalTrials.gov that’s being offered at MDA. Is this what he’s considering?
I’ve done IL-2 and ipilimumab as separate monotherapies, two years apart, and don’t have any personal experience with biochemo. With all of the newer treatment options available, I believe that biochemo is waning in popularity given a lower response rate and much higher toxicity profile as compared to the newer treatments, but perhaps there is some belief with this study that biochemo can boost the response rate of ipilimumab alone. And there are people who have had long-term responses to biochemo alone. From what I read on the trial information page linked above, it does sound like a rigorous treatment regimen, considering it involves both high-dose IL-2 and interferon along with the chemo.
My initial reaction to this was to wonder why they would suggest sequencing ipi/biochemo ahead of PD-1, but I imagine it has to do with the fact that both the current EAPs and with the expected approval of pembrolizumab soon, prior ipilimumab will be a requirement. So instead of just offering ipilimumab, they’re trying to give ipilimumab a better chance by trying it in combination with biochemo. Since it’s own approval, ipilimumab has been in combo trials with many different therapies, IL-2, BRAF inhibitors, TIL, biochemo (apparently), and nivolumab, among others. From what you’ve written, it sounds like Matt wants to be as aggressive as possible with his treatment, and this certainly qualifies. Is it a safe assumption that he is otherwise healthy? It can make all the difference when taking this approach.
If plan B becomes necessary (meaning Matt would have progressed on ipilimumab) by that time pembrolizumab should be approved, so that would be the next logical step. After that, plan C is TIL, about which I’m glad to share more details of the treatment when you’re ready for that information. It was 2011 when I went through it at NIH and I had a partial response; I also credit it with slowing my disease enough that we’ve been able to manage subsequent metastases (mostly to bone) one at a time as they’ve occurred. The core TIL treatment regimen itself hasn’t changed much and what is done at MDA is very similar to what is done at NCI and Moffitt. The important part right now is that he’s doing the tumor harvest now so that it can be banked and used later if needed — I think it’s great that MDA is offering that as an option now. You mentioned “infusions of TIL bathed in IL-2”; to clarify, the cells are grown in IL-2 over 4-6 weeks, but are given as a single infusion (over about 20 minutes), followed by a round of “standard” high-dose IL-2 treatment (3 infusions per day over about three days).
The ipilimumab/nivolumab combination trials are very interesting and all things being equal, something I’d personally consider as a first option faced with the choice today. However, all things aren’t equal and with the ipi/novo combo still in trials, there’s no guarantee what Matt would receive. He might get just nivo, just ipi, or the combo. There’s nothing wrong with that, but it’s a roll of the dice that you have to go into fully aware that what he’s hoping to get (the combo) he may not receive, and won’t know for sure what he’s getting for the duration of the trial. The randomized arms of a trial wouldn’t be an issue with the EAP, but I don’t know how widely available the EAP for the combo is yet. Considering that BMS’ nivolumab EAP seems to be be starting slowly as compared to Merck’s, it seems that the combo EAP is lagging the nivo-alone EAP.
So all told, I think plans A, B, and C in that order seem to be well-reasoned by the folks at MDA. I’ll qualify that with my own experience and that of many others by saying that planning out treatment for stage IV melanoma even three or six months in advance might be compared to herding cats, there are often unforeseen complications and twists and turns that can disrupt the best laid plans. Still, there is value in knowing the options and having a plan, and hopefully, plans B and C aren’t even needed.
I understand and respect the concerns Catherine, Dr. Flaherty, and others put forth about TIL, but I also take note that Matt is considering this as a plan C at this point, keeping his options open by having the cell harvest done now while there is a viable tumor available. Having had some success with TIL, I am (hopefully understandably) biased. As I said in my last post, the landscape has changed significantly since 2010 when I decided to go with TIL — my decision today might be different now than it was then, not because or any regrets but simply the wider range of options available today, but I’d consider doing it again in a retreatment scenario among my options if the need arises. My perspective is that TIL does have an uphill challenge to becoming a mainstream treatment, but not necessarily because of a lack of effectiveness. The big pharmaceuticals don’t seem all that interested in it, because it’s not typical drug development, it’s not a drug at all, but a process. As “personalized medicine”, it is currently a very manual process, from selecting the best T-cells from the tumor through the “babysitting” of those cells as they’re multiplied from thousands to tens of billions in the lab before infusion. It seems to me that the large pharmaceutical companies (and their big pockets) haven’t shown much interest, meaning that for now, only a handful of the largest medical centers have been willing to take it on with physician-sponsored trials and government funding via NIH. Lion Biotechnologies (formerly Genesis Biopharma) has a Cooperative Research and Development Agreement (CRADA) with the NCI and a non-exclusive licensing agreement with the NIH to try to “productize” and standardize the cell harvest and growth process, with the ultimate goal of enabling more hospitals to offer the treatment where they can harvest a tumor, send it off to a third-party lab, have the cells selected and grown, then sent back to the hospital for patient infusion. If Lion can accomplish that, then I’m guessing a large pharmaceutical will take notice and greater interest. Finally, I’ve followed TJ’s Patient #1 blog for quite some time, too, and yes, he started out in a trial at Moffitt that was a TIL/ipilimumab combo and he had disease progression, after which he’s had great success with PD-1, which has been great to hear. Also note his most recent posts, where he, too, went to MDA to have a new tumor harvested as an option for possible future retreatment with TIL if needed, just as Matt is seriously considering.
To answer your other specific question about how long after the harvest surgery it would be before Matt could start Yervoy and IL-2, I think it probably depends on from where the tumor is being resected. I actually started IL-2 about ten days after my harvest surgery (long story, one of the aforementioned twists and turns) — the stitches came out the day I was heading home after my first round of IL-2. But that was only IL-2 and not the other chemotherapies included with biochemo, and the harvested tumor was on my back, so pretty straightforward compared to an internal organ, for which they might want to wait a few weeks.
Again, hoping the information and perspective helps, and glad to try to answer other questions if I can. Please keep us up to date with what Matt ultimately decides to do and how things are going. Wishing you all the best.
JoeSeptember 4, 2014 at 6:28 pm #65321
Yes, I like to see numbers and randomized trials before I recommend a treatment. I do know of a few patients who have done well by TIL at NCI (not at MDA or Moffitt) and I also have faced the heartbreak of losing patients to the high toxicity associated with it. It is a very labor intensive procedure, costing at NCI, $500K per patient for the long series of procedures. Some of the therapies used, IL2 and Biochemo have very small response rates on their own (less than 6% for Il2 and biochemo has been dropped by most places.)
So weighing it all against the wonderful PD1 drugs with low toxicity and up to 80% response rates in some (low of 40%) that use our great new knowledge that working with our immune system provides a longer lasting response, I would choose PD1.September 10, 2014 at 2:35 am #65322
Hey Joey, thanks again for your detailed perspective! Yes, Matt wants treatment that is as aggressive as possible. He’s in good health, able to do just about everything under his own power. No health problems beyond the melanoma. No brain tumors. No coordination or cognitive problems. His right arm is sometimes in a sling, due to the pain from the shoulder met, but he’s still fairly robust. Just more easily tired.
He’s full speed ahead at MDA. He had a successful surgery today to excise part of the tumor under his left shoulder for the TIL harvest. I’m told the surgeon was able to get two full nodes/tumors, which really improves the chances for successfully growing T-cells. It looks like he’s scheduled to be admitted for the IL-2/ippy/etc. regimen in about two weeks.
One thing that my 77-year-old parents have noted several times now: MDA is an incredibly hospitable and efficient place. My mom has worked (and then volunteered) in one of Indiana’s largest hospitals for 30 years, and my dad is a studious consumer of health care, and they’re both VERY impressed with the staff and whole operation. For that matter, Matt is a medical-device salesman (urological) and certainly knows his way around the system, and he is sold on MDA.
So, it looks like we’re just waiting for the first phase of the treatment to start. Again, hopefully that’s no more than two weeks from now. Any advice on how to stay positive and hopeful during that lull?September 10, 2014 at 1:04 pm #65323
We wish Matt, his team and family, all the best on this journey. We are here to support you.
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